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A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle βo-thalassemia

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ClinicalTrials.gov Identifier: NCT01179217
Recruitment Status : Completed
First Posted : August 11, 2010
Results First Posted : August 10, 2017
Last Update Posted : August 10, 2017
Sponsor:
Information provided by (Responsible Party):
Emmaus Medical, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Sickle Cell Anemia
Sickle ß0-Thalassemia
Interventions Drug: L-glutamine
Drug: Placebo
Enrollment 230
Recruitment Details  
Pre-assignment Details  
Arm/Group Title L-glutamine Placebo
Hide Arm/Group Description

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo (100% maltodextrin): 0.3 g/kg of placebo will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Period Title: Overall Study
Started 152 78
Completed 97 59
Not Completed 55 19
Arm/Group Title L-glutamine Placebo Total
Hide Arm/Group Description

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Total of all reporting groups
Overall Number of Baseline Participants 152 78 230
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 78 participants 230 participants
<=18 years
75
  49.3%
43
  55.1%
118
  51.3%
Between 18 and 65 years
77
  50.7%
35
  44.9%
112
  48.7%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 78 participants 230 participants
22.4  (12.32) 21.4  (12.42) 22.0  (12.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 78 participants 230 participants
Female
79
  52.0%
45
  57.7%
124
  53.9%
Male
73
  48.0%
33
  42.3%
106
  46.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 78 participants 230 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
144
  94.7%
73
  93.6%
217
  94.3%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
8
   5.3%
5
   6.4%
13
   5.7%
Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 78 participants 230 participants
Sickle Cell Anemia
136
  89.5%
71
  91.0%
207
  90.0%
Sickle Beta plus Thalassemia
2
   1.3%
0
   0.0%
2
   0.9%
Sickle Beta zero Thalassemia
14
   9.2%
7
   9.0%
21
   9.1%
1.Primary Outcome
Title The Number of Occurrences of Sickle Cell Crises
Hide Description The number of occurrences of protocol-defined sickle cell crises that occur from Week 0 to Week 48 will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 152 78
Median (Full Range)
Unit of Measure: Number of crises
3
(0 to 15)
4
(0 to 15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection L-glutamine, 100% Maltodextrin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments
  1. The primary analysis was analyzed using a CMH analysis of the number of SCCs using modified ridit scores.
  2. P-value (controlling for region and HU use)
  3. The null hypothesis of the final analysis was performed at the 0.045 significance level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Wilcoxon rank-sum test
Estimated Value 0.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Number of Hospitalizations for Sickle Cell Pain
Hide Description The number of hospitalizations that occur from Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 152 78
Median (Full Range)
Unit of Measure: Number of hospitalizations
2
(0 to 14)
3
(0 to 13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection L-glutamine, 100% Maltodextrin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Secondary Outcome
Title The Number of Emergency Room/Medical Facility Visits for Sickle Cell Pain
Hide Description The number of emergency room visits or medical facility visits that occur from Week 0 to Week 48, will be used to evaluate the efficacy of oral L-glutamine as a treatment for sickle cell anemia and beta-0 thalassemia.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population - Included all patients who were randomized and dispensed study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 152 78
Median (Full Range)
Unit of Measure: Number of ER visits
1
(0 to 12)
1
(0 to 15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection L-glutamine, 100% Maltodextrin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0888
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title The Effect of Oral -L-glutamine on Hematological Parameters
Hide Description To assess the effect of oral L-glutamine on hematological parameters (hemoglobin), Change from Baseline will be reported at Weeks 4, 24 and 48.
Time Frame Baseline, Week 4, 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population - The safety population included all patients who received at least 1 dose of study medication.
Arm/Group Title L-glutamine Placebo
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo (100% maltodextrin): 0.3 g/kg of placebo will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: g/dL
Hemoglobin at Baseline Number Analyzed 151 participants 78 participants
8.82  (1.43) 8.71  (1.17)
Change in Hemoglobin at week 4 Number Analyzed 134 participants 69 participants
0.04  (0.84) 0.23  (0.71)
Change in Hemoglobin at Week 24 Number Analyzed 99 participants 61 participants
-0.17  (1.01) -0.12  (1.24)
Change in Hemoglobin at Week 48 Number Analyzed 80 participants 47 participants
-0.12  (0.95) -0.12  (0.96)
5.Secondary Outcome
Title The Effect of Oral L-glutamine on Vital Signs
Hide Description To assess the effect of oral L-glutamine on Vital signs (systolic and diastolic blood pressure). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame Baseline, Week 4, 24, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population which includes all patients that took at least one dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: mm Hg
Systolic blood pressure at Baseline Number Analyzed 151 participants 78 participants
111.3  (11.20) 114.6  (14.16)
Change Systolic blood pressure at Week 4 Number Analyzed 134 participants 73 participants
0.5  (11.19) -0.2  (10.68)
Change in Systolic blood pressure at Week 24 Number Analyzed 102 participants 63 participants
1.1  (10.78) 0.5  (14.23)
Change in Systolic blood pressure at Week 48 Number Analyzed 86 participants 51 participants
2.2  (10.78) 2.6  (15.70)
Diastolic blood pressure at Baseline Number Analyzed 151 participants 78 participants
64.8  (8.61) 66.2  (9.75)
Change in Diastolic blood pressure at Week 4 Number Analyzed 134 participants 73 participants
-0.7  (9.08) 0.3  (10.29)
Change in Diastolic blood pressure at Week 24 Number Analyzed 102 participants 63 participants
-0.7  (8.40) 0.6  (12.44)
Change in Diastolic blood pressure at Week 48 Number Analyzed 86 participants 51 participants
0.4  (8.71) 2.0  (9.96)
6.Secondary Outcome
Title The Effect of Oral L-glutamine on Hematological Parameters
Hide Description To assess the effect of oral L-glutamine on hematological parameters (hematocrit), Change from Baseline will be reported at Weeks 4, 24 and 48.
Time Frame Baseline, Week 4, 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population - The safety population included all patients who received at least 1 dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: % of red blood cells
Hematocrit at Baseline 27.67  (4.40) 27.53  (3.61)
Change in Hematocrit at Week 4 0.16  (2.77) 0.75  (2.52)
Change in Hematocrit Week 24 -0.26  (3.42) -0.15  (4.13)
Change in Hematocrit at Week 48 0.16  (3.27) 0.11  (3.19)
7.Secondary Outcome
Title The Effect of Oral L-glutamine on Hematological Parameters
Hide Description To assess the effect of oral L-glutamine on hematological parameters (reticulocyte count), Change from Baseline will be reported at Weeks 4, 24 and 48.
Time Frame Baseline, Week 4, 24 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population - The safety population included all patients who received at least 1 dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: 1000 cells/uL
Reticulocyte (Abs) 283.62  (129.49) 295.03  (140.10)
Change in Reticulocyte (Abs) at Week 4 -9.28  (104.88) -23.09  (160.41)
Change in Reticulocyte (Abs) at Week 24 7.94  (111.85) -1.93  (137.65)
Change in Reticulocyte (Abs) at Week 48 50.89  (112.93) 26.27  (140.65)
8.Secondary Outcome
Title The Effect of Oral L-glutamine on Vital Signs
Hide Description To assess the effect of oral L-glutamine on Vital signs (pulse rate). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame Baseline, Week 4, Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population which includes all patients that took at least one dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: bpm
Pulse Rate (bpm) at Baseline Number Analyzed 151 participants 78 participants
85.6  (13.15) 88.5  (14.07)
Change in Pulse Rate (bpm) at Week 4 Number Analyzed 134 participants 73 participants
-0.1  (12.07) -0.4  (14.96)
Change in Pulse Rate (bpm) at Week 24 Number Analyzed 102 participants 63 participants
3.0  (14.58) -1.5  (15.05)
Change in Pulse Rate (bpm) at 48 Number Analyzed 86 participants 51 participants
1.1  (14.74) 0.2  (15.33)
9.Secondary Outcome
Title Effect of Oral L-glutamine on Vital Signs
Hide Description To assess the effect of oral L-glutamine on Vital signs (temperature). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame Baseline, Week 4, Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population which includes all patients that took at least one dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: degree C
Temperature at Baseline Number Analyzed 151 participants 78 participants
36.85  (0.387) 36.83  (0.403)
Change in Temperature at Week 4 Number Analyzed 135 participants 73 participants
-0.06  (0.436) -0.02  (0.540)
Change in Temperature at Week 24 Number Analyzed 102 participants 63 participants
-0.05  (0.469) 0.03  (0.510)
Change in Temperature at Week 48 Number Analyzed 86 participants 51 participants
-0.09  (0.442) 0.05  (0.521)
10.Secondary Outcome
Title The Effect of Oral L-glutamine on Vital Signs
Hide Description To assess the effect of oral L-glutamine on Vital signs (respiration). Change from Baseline will be reported at Weeks 4, 24, and 48.
Time Frame Baseline, Week 4, Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population which includes all patients that took at least one dose of study medication.
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description:

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

Placebo: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

Overall Number of Participants Analyzed 151 78
Mean (Standard Deviation)
Unit of Measure: breaths/min
Respiration at Baseline Number Analyzed 151 participants 78 participants
18.9  (3.0) 19.1  (2.34)
Change in Respiration at Week 4 Number Analyzed 133 participants 73 participants
-0.2  (3.01) -0.2  (2.55)
Change in Respiration at Week 24 Number Analyzed 101 participants 63 participants
-0.7  (3.03) -0.6  (3.36)
Change in Respiration at Week 48 Number Analyzed 85 participants 51 participants
-0.7  (3.25) -0.6  (2.94)
Time Frame Adverse events data were collected throughout the course of the study (53 weeks or about 1 year).
Adverse Event Reporting Description The Safety population will include all patients who received at least one dose of study medication.
 
Arm/Group Title L-glutamine 100% Maltodextrin
Hide Arm/Group Description

Patients will be randomized to receive investigational product, L-Glutamine.

L-glutamine: 0.3 g/kg of L-glutamine will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration. Mixing L-glutamine with soda or highly acidic juices (such as grapefruit juice or lemonade) is not recommended.

Patients will be randomized to receive Placebo.

100% maltodextrin: 0.3 g/kg of placebo (100% maltodextrin) will be administered twice a day orally to each patient for 48 weeks. The dosage will be in increments of 5 grams based on weight. The upper limit for daily dose of study medication will be set at 30 grams. Patients will be given verbal and written instructions for self-administration of the study medication at the Baseline visit. The powder can be mixed with water or most non-heated beverages other than alcohol, or can be mixed with most non-heated foods such as yogurt, applesauce, or cereal for administration.

All-Cause Mortality
L-glutamine 100% Maltodextrin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
L-glutamine 100% Maltodextrin
Affected / at Risk (%) Affected / at Risk (%)
Total   118/151 (78.15%)   68/78 (87.18%) 
Blood and lymphatic system disorders     
Acute Chest Syndrome  1  12/151 (7.95%)  18/78 (23.08%) 
Anaemia  1  1/151 (0.66%)  2/78 (2.56%) 
Aplastic anaemia  1  1/151 (0.66%)  0/78 (0.00%) 
Haemolysis  1  1/151 (0.66%)  0/78 (0.00%) 
Hypersplenism  1  2/151 (1.32%)  0/78 (0.00%) 
Leucocytosis  1  1/151 (0.66%)  0/78 (0.00%) 
Lymphadenopathy  1  0/151 (0.00%)  0/78 (0.00%) 
Cardiac disorders     
Cardiac Arrest  1  2/151 (1.32%)  1/78 (1.28%) 
Cardiac failure  1  0/151 (0.00%)  1/78 (1.28%) 
Cardiac failure congestive  1  0/151 (0.00%)  1/78 (1.28%) 
Congenital, familial and genetic disorders     
Sickle cell anaemia with crisis  1  102/151 (67.55%)  63/78 (80.77%) 
Eye disorders     
Eye irritation  1  0/151 (0.00%)  1/78 (1.28%) 
Gastrointestinal disorders     
Abdominal pain  1  3/151 (1.99%)  3/78 (3.85%) 
Abdominal pain upper  1  1/151 (0.66%)  0/78 (0.00%) 
Constipation  1  1/151 (0.66%)  1/78 (1.28%) 
Gastritis  1  1/151 (0.66%)  1/78 (1.28%) 
Nausea  1  1/151 (0.66%)  0/78 (0.00%) 
Pancreatic acute  1  0/151 (0.00%)  1/78 (1.28%) 
Vomiting  1  2/151 (1.32%)  1/78 (1.28%) 
General disorders     
Chest pain  1  5/151 (3.31%)  1/78 (1.28%) 
Death  1  1/151 (0.66%)  0/78 (0.00%) 
Drug withdrawal syndrome  1  0/151 (0.00%)  1/78 (1.28%) 
Necrosis  1  0/151 (0.00%)  1/78 (1.28%) 
Oedema peripheral  1  2/151 (1.32%)  0/78 (0.00%) 
Pain  1  1/151 (0.66%)  0/78 (0.00%) 
Pyrexia  1  6/151 (3.97%)  3/78 (3.85%) 
Cholelithiasis  1  1/151 (0.66%)  0/78 (0.00%) 
Hyperbilirubinaemia  1  0/151 (0.00%)  1/78 (1.28%) 
Hepatobiliary disorders     
Cholecystitis  1  1/151 (0.66%)  0/78 (0.00%) 
Cholecystitis acute  1  1/151 (0.66%)  0/78 (0.00%) 
Immune system disorders     
Hypersensitivity  1  0/151 (0.00%)  1/78 (1.28%) 
Infections and infestations     
Bronchitis  1  1/151 (0.66%)  1/78 (1.28%) 
Gastroenteritis  1  0/151 (0.00%)  2/78 (2.56%) 
Gastrointestinal viral infection  1  1/151 (0.66%)  0/78 (0.00%) 
Influenza  1  3/151 (1.99%)  1/78 (1.28%) 
Lobar pneumonia  1  1/151 (0.66%)  0/78 (0.00%) 
Osteomyelitis  1  1/151 (0.66%)  0/78 (0.00%) 
Osteomyelitis acute  1  0/151 (0.00%)  1/78 (1.28%) 
Pharnygitis streptococcal  1  1/151 (0.66%)  1/78 (1.28%) 
Pneumonia  1  3/151 (1.99%)  8/78 (10.26%) 
Sepsis  1  1/151 (0.66%)  0/78 (0.00%) 
Sinustitis  1  1/151 (0.66%)  1/78 (1.28%) 
Tonsilitis  1  0/151 (0.00%)  1/78 (1.28%) 
Tooth infection  1  0/151 (0.00%)  1/78 (1.28%) 
Upper respiratory tract infection  1  1/151 (0.66%)  0/78 (0.00%) 
Urinary tract infection  1  0/151 (0.00%)  1/78 (1.28%) 
Injury, poisoning and procedural complications     
Complication of device removal  1  1/151 (0.66%)  0/78 (0.00%) 
Device leakage  1  0/151 (0.00%)  1/78 (1.28%) 
Device malfunction  1  2/151 (1.32%)  0/78 (0.00%) 
Device occlusion  1  0/151 (0.00%)  1/78 (1.28%) 
Fall  1  1/151 (0.66%)  0/78 (0.00%) 
Haemolytic transfusion reaction  1  1/151 (0.66%)  0/78 (0.00%) 
Ligament rupture  1  0/151 (0.00%)  1/78 (1.28%) 
Post-traumatic reaction  1  1/151 (0.66%)  0/78 (0.00%) 
Traumatic arthropathy  1  0/151 (0.00%)  1/78 (1.28%) 
Investigations     
Blood creatinine increased  1  0/151 (0.00%)  1/78 (1.28%) 
White blood cell count increased  1  0/151 (0.00%)  1/78 (1.28%) 
Hyperkalaemia  1  0/151 (0.00%)  1/78 (1.28%) 
Metabolism and nutrition disorders     
Dehydration  1  2/151 (1.32%)  2/78 (2.56%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/151 (0.00%)  1/78 (1.28%) 
Arthropathy  1  0/151 (0.00%)  1/78 (1.28%) 
Back pain  1  3/151 (1.99%)  1/78 (1.28%) 
Bunion  1  0/151 (0.00%)  1/78 (1.28%) 
Bone infarction  1  0/151 (0.00%)  1/78 (1.28%) 
Joint effusion  1  1/151 (0.66%)  0/78 (0.00%) 
Musculoskeletal pain  1  0/151 (0.00%)  1/78 (1.28%) 
Osteoarthritis  1  0/151 (0.00%)  1/78 (1.28%) 
Osteonecrosis  1  0/151 (0.00%)  1/78 (1.28%) 
Pain in extremity  1  2/151 (1.32%)  0/78 (0.00%) 
Nervous system disorders     
Dysarthria  1  0/151 (0.00%)  1/78 (1.28%) 
Headache  1  1/151 (0.66%)  1/78 (1.28%) 
Migraine  1  0/151 (0.00%)  1/78 (1.28%) 
Transient ischaemic attack  1  2/151 (1.32%)  0/78 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy  1  2/151 (1.32%)  2/78 (2.56%) 
Psychiatric disorders     
Mental status changes  1  0/151 (0.00%)  1/78 (1.28%) 
Renal and urinary disorders     
Haematuria  1  1/151 (0.66%)  0/78 (0.00%) 
Renal failure acute  1  1/151 (0.66%)  1/78 (1.28%) 
Reproductive system and breast disorders     
Priapism  1  0/151 (0.00%)  1/78 (1.28%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  4/151 (2.65%)  0/78 (0.00%) 
Bronchial hyperreactivity  1  1/151 (0.66%)  0/78 (0.00%) 
Cough  1  1/151 (0.66%)  0/78 (0.00%) 
Dyspnoea  1  1/151 (0.66%)  0/78 (0.00%) 
Haemothorax  1  0/151 (0.00%)  1/78 (1.28%) 
Hypoxia  1  1/151 (0.66%)  2/78 (2.56%) 
Pulmonary embolism  1  1/151 (0.66%)  1/78 (1.28%) 
Respiratory depression  1  0/151 (0.00%)  1/78 (1.28%) 
Respiratory distress  1  0/151 (0.00%)  1/78 (1.28%) 
Rhinitis allergic  1  1/151 (0.66%)  0/78 (0.00%) 
Skin and subcutaneous tissue disorders     
Skin ulcer  1  2/151 (1.32%)  0/78 (0.00%) 
Surgical and medical procedures     
Hip arthroplasty  1  0/151 (0.00%)  1/78 (1.28%) 
Strabismus correction  1  1/151 (0.66%)  0/78 (0.00%) 
Tonsillectomy  1  0/151 (0.00%)  1/78 (1.28%) 
Vascular disorders     
Deep vein thrombosis  1  2/151 (1.32%)  0/78 (0.00%) 
Thrombophlebits superficial  1  1/151 (0.66%)  0/78 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
L-glutamine 100% Maltodextrin
Affected / at Risk (%) Affected / at Risk (%)
Total   148/151 (98.01%)   78/78 (100.00%) 
Blood and lymphatic system disorders     
Acute chest syndrome  1  18/151 (11.92%)  21/78 (26.92%) 
Leukocytosis  1  9/151 (5.96%)  6/78 (7.69%) 
Anaemia  1  7/151 (4.64%)  6/78 (7.69%) 
Cardiac disorders     
Tachycardia  1  8/151 (5.30%)  4/78 (5.13%) 
Congenital, familial and genetic disorders     
Sickle cell anaemia with crisis  1  123/151 (81.46%)  71/78 (91.03%) 
Eye disorders     
Ocular icterus  1  15/151 (9.93%)  9/78 (11.54%) 
Gastrointestinal disorders     
Constipation  1  38/151 (25.17%)  19/78 (24.36%) 
Nausea  1  34/151 (22.52%)  13/78 (16.67%) 
Vomiting  1  22/151 (14.57%)  10/78 (12.82%) 
Abdominal pain  1  18/151 (11.92%)  10/78 (12.82%) 
Abdominal pain upper  1  16/151 (10.60%)  6/78 (7.69%) 
Diarrhoea  1  12/151 (7.95%)  5/78 (6.41%) 
General disorders     
Pyrexia  1  33/151 (21.85%)  29/78 (37.18%) 
Chest pain  1  21/151 (13.91%)  7/78 (8.97%) 
Fatigue  1  9/151 (5.96%)  1/78 (1.28%) 
Oedema peripheral  1  8/151 (5.30%)  8/78 (10.26%) 
Infections and infestations     
Upper respiratory tract infection  1  27/151 (17.88%)  18/78 (23.08%) 
Nasopharyngitis  1  10/151 (6.62%)  6/78 (7.69%) 
Urinary tract infection  1  10/151 (6.62%)  3/78 (3.85%) 
Pneumonia  1  9/151 (5.96%)  14/78 (17.95%) 
Bronchitis  1  5/151 (3.31%)  4/78 (5.13%) 
Gastroenteritis  1  5/151 (3.31%)  4/78 (5.13%) 
Investigations     
Hypomanesaemia  1  6/151 (3.97%)  4/78 (5.13%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  6/151 (3.97%)  5/78 (6.41%) 
Hyperkalaemia  1  5/151 (3.31%)  4/78 (5.13%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  24/151 (15.89%)  6/78 (7.69%) 
Back pain  1  20/151 (13.25%)  5/78 (6.41%) 
Arthralgia  1  19/151 (12.58%)  10/78 (12.82%) 
Nervous system disorders     
Headache  1  32/151 (21.19%)  14/78 (17.95%) 
Dizziness  1  8/151 (5.30%)  4/78 (5.13%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  26/151 (17.22%)  14/78 (17.95%) 
Nasal congestion  1  11/151 (7.28%)  5/78 (6.41%) 
Oropharnyngeal pain  1  11/151 (7.28%)  11/78 (14.10%) 
Dyspnoea  1  8/151 (5.30%)  7/78 (8.97%) 
Hypoxia  1  5/151 (3.31%)  4/78 (5.13%) 
Epistaxis  1  4/151 (2.65%)  6/78 (7.69%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  14/151 (9.27%)  11/78 (14.10%) 
Rash  1  3/151 (1.99%)  14/78 (17.95%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI agrees that any INFORMATION submitted to it by EMMAUS shall be maintained in secrecy for a period of seven (7) years from each disclosure of INFORMATION. PI will use the up most due diligence to prevent disclosure by it except to its employees, agents, and contractors necessary for evaluation, all of whom shall be bound by similar written obligations of confidentiality, and who agree not to use the INFORMATION for any purpose other than for evaluation purposes.
Results Point of Contact
Name/Title: Yutaka Niihara, MD, MPH
Organization: Emmaus Medical, Inc
Phone: 310-214-0065
Responsible Party: Emmaus Medical, Inc.
ClinicalTrials.gov Identifier: NCT01179217     History of Changes
Other Study ID Numbers: GLUSCC09-01
First Submitted: May 21, 2010
First Posted: August 11, 2010
Results First Submitted: December 14, 2016
Results First Posted: August 10, 2017
Last Update Posted: August 10, 2017