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L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia

This study has been completed.
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Emmaus Medical, Inc.
ClinicalTrials.gov Identifier:
NCT00125788
First received: August 1, 2005
Last updated: August 7, 2017
Last verified: August 2017
  Purpose
The purpose of this research is to evaluate the effects of L-glutamine as a therapy for sickle cell anemia and sickle ß0-thalassemia. as evaluated by the number of occurrences of sickle cell crises.

Condition Intervention Phase
Sickle Cell Anemia Thalassemia Drug: L-glutamine Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of L Glutamine Therapy for Sickle Cell Anemia and Sickle ß0-Thalassemia

Resource links provided by NLM:


Further study details as provided by Emmaus Medical, Inc.:

Primary Outcome Measures:
  • Number of occurrences of painful sickle cell crises [ Time Frame: from Week 0 through Week 48 (cumulative) ]
    The mean number of painful sickle crisis through week 48


Secondary Outcome Measures:
  • Frequency of hospitalizations for sickle cell pain [ Time Frame: From Week 0 through Week 24 (cumulative), and from Week 0 through Week 48 (cumulative) ]
    The mean number of hospitalizations through week 48

  • Frequency of emergency room visits for sickle cell pain [ Time Frame: from Week 0 through Week 24 (cumulative), and from Week 0 through Week 48 (cumulative) ]
    The mean number of emergency room visits through week 48

  • Number of days patients' usual daily activities are interrupted due to sickle cell pain [ Time Frame: From Week 0 through Week 48 (cumulative) ]
    The mean change of interruption of usual daily activities through week 48

  • Growth curve for patients less than 18 years of age [ Time Frame: At each study visit (approximately every four weeks) ]
    At each study visit, the patient's height and weight will be compared to the standard growth curve. The patient will be classified as below the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentile for height and weight (mutually exclusive groups).

  • Hematological parameters [ Time Frame: Collected at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48, 53 ]
    Hemoglobin, hematocrit, reticulocyte counts

  • Narcotic usage [ Time Frame: From from Week 0 through Week 48 ]
    Analysis of narcotic usage was perfromed for the subset of patients with any narcotic use who completed the study. Changes in narcotic usage were determined by na independent consultant prior to database lock using morphine equivalents to determine relative use.

  • Alcohol and tobacco use [ Time Frame: From Week 0 through Week 48 ]
    A regression analysis was to be performed using month as the independent variable and alcohol as the dependent variable to test if alcohol usage decreased over the study for each treatment group. The slopes of the two treatment groups were to be compared. The same approach was to be used for tobacco usage.

  • Pain level (11-point scale) [ Time Frame: assessed at each study visit from Week 0 through Week 48 (approximately every four weeks) ]
    The treatment groups were compared at each visit with respect to change from baseline in the severity of the patient's pain using an ANOVA with treatment group and study center in the model.

  • Energy level (11-point scale) [ Time Frame: assessed at each study visit from Week 0 through Week 48 (approximately every four weeks) ]
    The treatment groups were compared at each visit with respect to change from baseline in the level of the patient's energy using an ANOVA with treatment group and study center in the model.

  • Patient activity level (3-point scale) [ Time Frame: assessed at each study visit from Week 0 through Week 48 (approximately every four weeks) ]
    The percentages of patients at each visit whose activity was below, normal, or above average were compared using CMH test controlling for study center.

  • Patient appetite (3-point scale) [ Time Frame: assessed at each study visit from Week 0 through Week 48 (approximately every four weeks) ]
    The percentages of patients at each visit whose appetite was below, normal, or above average were compared using CMH test controlling for study center.

  • Subjective exercise tolerance [ Time Frame: assessed at each study visit from Week 0 through Week 48 (approximately every four weeks) ]
    The treatment groups were compared for each of the 4 measures of subjective exercise tolerance (minutes patient could walk without rest, minutes patient could run without rest, distance a patient could walk without rest, and distance a patient could run without rest) at each visit with respect to the change in minutes or distance using an ANOVA with treatment group and study center in the model.

  • Subjective quality of life [ Time Frame: assessed at Baseline, Week 24, and Early Withdrawal visits ]

    For the subjective quality of life, the RAND-36 Item Health Survery 1.0 will be administered to adults (greater than or equal to 18 years) at baseline,Week 24, or Early Withdrawal visits. The RAND survey uses eight health concepts: physical functioning, bodily pain, role limitations, due to physical problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions.

    For the subjective quality of life, the Pediatric Quality of Life questionnaires will be administered to children and adolescents (greater than or equal to 5 years and less than or equal to 17 years) at baseline, Week 24, and Early Withdrawal visits.


  • L-glutamine safety assessment based on adverse events, laboratory parameters, and vital signs [ Time Frame: ongoing from Week 0 through Week 53 ]
    No statistical tests were performed for the safety vaiables,

  • Number of occurrences of sickle cell crises [ Time Frame: from Week 0 through Week 24 (cumulative) ]
    The treatment groups were compared with respect to the number of sickle cell crises. This analysis was performed on both the full analysis and per-protocol datasets.


Enrollment: 81
Study Start Date: March 2004
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: investigational product
L-glutamine
Drug: L-glutamine
Approximately 0.3 g/kg total daily dose of L-glutamine will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Other Name: oral L-glutamine
Placebo Comparator: placebo
maltodextrin
Drug: Placebo
Approximately 0.3 g/kg total daily dose of maltodextrin placebo will be orally administered (over two doses), with a maximum total daily dose of 30 grams.
Other Name: maltodextrin

Detailed Description:

The primary purpose of this study is to evaluate the effectiveness of oral L-glutamine in the therapy of sickle cell anemia and sickle ß0-thalassemia.

The secondary purpose is to assess the effect of L-glutamine on pain; energy and appetite levels; narcotics usage; height and weight; and hospital and emergency room visits for sickle cell pain.

Methodology:

By site, patients will be randomized to L-glutamine or placebo in a 1:1 ratio after a 4-week screening period. Patients will undergo 48 weeks of treatment with dosing BID orally, with dose calculated according to patient weight. Patient visits will occur every 4 weeks. After 48 weeks of treatment, dose will be tapered to zero within 3 weeks. A final evaluation visit will occur 2 weeks after last dose.

  Eligibility

Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible to participate in the study, a patient must meet all of the following inclusion criteria:

  • Patient is at least five years of age.
  • Patient has been diagnosed with sickle cell anemia or sickle ß0-thalassemia (documented by hemoglobin electrophoresis).
  • Patient has had at least two episodes of painful crises within 12 months of the screening visit.
  • If the patient has been treated with an anti-sickling agent within three months of the screening visit, the therapy must have been continuous for at least three months with the intent to continue for the next 14 months.
  • Patient or the patient's legally authorized representative has given written informed consent.
  • If the patient is a female of child-bearing potential, she agrees to practice a recognized form of birth control during the course of the study.

Exclusion Criteria:

If the patient meets any of the following criteria, the patient must not be enrolled:

  • Patient has a significant medical condition that required hospitalization (other than sickle painful crisis) within two months of the screening visit.
  • Patient has diabetes mellitus with untreated fasting blood sugar >115 mg/dL.
  • Patient has prothrombin time International Normalized Ratio (INR) > 2.0.
  • Patient has serum albumin < 3.0 g/dl.
  • Patient has received any blood products within three weeks of the screening visit.
  • Patient has a history of uncontrolled liver disease or renal insufficiency.
  • Patient is pregnant or lactating.
  • Patient has been treated with an experimental anti-sickling medication/treatment (except hydroxyurea) within 30 days of the screening visit.
  • Patient has been treated with an experimental drug within 30 days of the screening visit.
  • There are factors that would, in the judgment of the investigator, make it difficult for the patient to comply with the requirements of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125788

Locations
United States, California
Kaiser Permanente
Bellflower, California, United States, 90706
Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
United States, New Jersey
University of Medicine and Dentistry, New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
Jacobi Medical Center
The Bronx, New York, United States, 10461
Sponsors and Collaborators
Emmaus Medical, Inc.
FDA Office of Orphan Products Development
Investigators
Principal Investigator: Yutaka Niihara, MD CEO, Emmaus Medical, Inc
  More Information

Responsible Party: Emmaus Medical, Inc.
ClinicalTrials.gov Identifier: NCT00125788     History of Changes
Obsolete Identifiers: NCT00029887
Other Study ID Numbers: 10478
Study First Received: August 1, 2005
Last Updated: August 7, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Emmaus Medical, Inc.:
sickle cell disease
sickle cell anemia
L-glutamine
Sickle Cell Anemia (homozygous)
Sickle ß0-Thalassemia

Additional relevant MeSH terms:
Anemia
Thalassemia
Anemia, Sickle Cell
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on August 21, 2017