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Trial record 39 of 337 for:    Charcot Marie Tooth

L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1

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ClinicalTrials.gov Identifier: NCT01733407
Recruitment Status : Completed
First Posted : November 27, 2012
Results First Posted : September 12, 2018
Last Update Posted : September 12, 2018
Sponsor:
Information provided by (Responsible Party):
Florian Eichler, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hereditary Sensory and Autonomic Neuropathy Type I
Interventions Drug: L-serine
Drug: placebo
Enrollment 18
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Period Title: Overall Study
Started 9 9
Completed 7 9
Not Completed 2 0
Arm/Group Title Sugar Pill L-serine Total
Hide Arm/Group Description

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Total of all reporting groups
Overall Number of Baseline Participants 9 9 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
8
  88.9%
9
 100.0%
17
  94.4%
>=65 years
1
  11.1%
0
   0.0%
1
   5.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 9 participants 18 participants
49.9  (16.9) 45.8  (11.0) 47.8  (14.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
Female
4
  44.4%
8
  88.9%
12
  66.7%
Male
5
  55.6%
1
  11.1%
6
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 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
0
   0.0%
0
   0.0%
0
   0.0%
White
9
 100.0%
9
 100.0%
18
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
United States
8
  88.9%
9
 100.0%
17
  94.4%
Canada
1
  11.1%
0
   0.0%
1
   5.6%
Charcot-Marie-Tooth Neuropathy Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 9 participants 9 participants 18 participants
24.6  (7.0) 20.6  (10.0) 22.6  (8.6)
[1]
Measure Description: The Charcot Marie Tooth Neuropathy Score (CMTNS) is a 36-point composite scoring assessment that assesses disease severity in neuropathies. It is composed of 9 items that evaluate functions related to disease progression including assessing sensory symptoms, motor symptoms, pinprick sensibility, vibration, leg strength, arm strength, and nerve conduction tests. Each item is scored from 0 to 4 with the lower scores representing less severe symptoms and higher scores representing more severe symptoms.The individual item scores are then totaled to provide a global measure of disease severity
1.Primary Outcome
Title Charcot Marie Tooth Neuropathy Score
Hide Description The Charcot Marie Tooth Neuropathy Score (CMTNS) is a 0 to 36 point composite scoring assessment that is used to measure disease severity in Charcot Marie Tooth Neuropathy and other sensory and motor neuropathies. The CMTNS is composed of 9 items that evaluate functions related to disease progression. These 9 parameters include reviewing sensory symptoms, motor symptoms (arms and legs), pinprick sensibility, vibration, leg strength, arm strength, and nerve conduction tests. Each item is scored from 0 to 4, with the lower scores representing less severe symptoms and higher scores representing more severe symptoms.The 9 individual item scores are then totaled to provide a global measure of disease severity. For example the lowest possible total score is 0 which represents an asymptomatic individual and the highest score possible is a 36 which represents an individual with severe disease progression. There are sub scores that can be assessed but sub scores were not utilized in this study
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: scores on a scale
25.67  (6.69) 20.22  (10.10)
2.Secondary Outcome
Title Intraepidermal Nerve Fiber Density (IENFD)
Hide Description Counts of nerve fibers per unit area in skin biopsies
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: nerve fibers per micrometer^2
Upper Thigh 34.67  (35.12) 49.56  (43.44)
Lower Calf 0.89  (2.67) 13.89  (24.10)
3.Secondary Outcome
Title Autonomic Function Testing (AFT) Composite Autonomic Severity Score (CASS)
Hide Description Autonomic Function Testing (AFT) tests the effectiveness of your autonomic nervous system which regulates important functions such as blood pressure, heart rate, and respiration. AFT results are quantified using the composite autonomic severity score scale (CASS) which is a scale from 0 to 10 that is the sum of three sub scores (cardiovagal, adrenergic, and sudomotor). Cardiovagal is scored from 0 to 3, sudomotor is scored from 0 to 3, and adrenergic is scored from 0 to 4. The tests include deep breathing, Valsalva maneuver, head-up tilt, and a sweat test. The three subscores are then summed. This total represents the CASS which classifies autonomic function as normal functioning (total score 0), mild (total score 1-3), moderate (total score 4-6), or severe (total score 7-10).
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: scores on a scale
3.56  (1.24) 2.22  (1.64)
4.Secondary Outcome
Title Nerve Conduction Testing
Hide Description Evaluates the functioning of electrical conduction of the motor and sensory nerves of the human body.
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Error)
Unit of Measure: microvolts
Sensrory Right Median Amplitude 1.34  (4.03) 5.51  (9.27)
Sensory Right Antebrach Amplitude 2.31  (3.94) 5.89  (9.54)
Sensory Right Superficial Radial Amplitude 4.56  (10.17) 10.84  (20.11)
Sensory Right Sural Amplitude 0.52  (1.57) 1.07  (2.61)
Sensory Right Superficial Peroneal Amplitude 0.00  (0.00) 0.00  (0.00)
Motor Right Median (Wrist) Amplitude 3.34  (4.52) 4.21  (4.29)
Motor Right Ulnar (Wrist) Amplitude 2.49  (3.60) 4.37  (4.80)
Motor Right Peroneal EDB (Ankle) Amplitude 0.54  (1.52) 0.24  (0.66)
Motor Right Peroneal Tib (Below) Amplitude 0.29  (0.47) 1.39  (2.15)
5.Secondary Outcome
Title 1-deoxy-sphinganine
Hide Description Plasma levels of the deoxysphingoid lipid 1-deoxy-sphinganine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups
Time Frame 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: micromole per liter
0.338  (0.191) 0.112  (0.042)
6.Secondary Outcome
Title 1-deoxy-sphingosine
Hide Description Plasma levels of the deoxysphingoid lipid 1-deoxy-sphingosine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups
Time Frame 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description:

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

Overall Number of Participants Analyzed 9 9
Mean (Standard Deviation)
Unit of Measure: micromole per liter
0.698  (0.306) 0.337  (0.132)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sugar Pill L-serine
Hide Arm/Group Description

Placebo arm

placebo: 400mg/kg/d divided TID for year 1 only.

amino acid supplementation with L-serine

L-serine: 400mg/kg/d L-serine or placebo divided TID for year 1, then crossover of placebo arm so that all patients on 400mg/kg/d L-serine divided TID for year 2.

All-Cause Mortality
Sugar Pill L-serine
Affected / at Risk (%) Affected / at Risk (%)
Total   1/9 (11.11%)      0/9 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Sugar Pill L-serine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/9 (11.11%)      1/9 (11.11%)    
Gastrointestinal disorders     
Esophageal Cancer * [1]  1/9 (11.11%)  1 0/9 (0.00%)  0
Infections and infestations     
MRSA Staff Infection  [2]  0/9 (0.00%)  0 1/9 (11.11%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Subject developed esophageal cancer
Indicates events were collected by systematic assessment
[2]
Hospitalized for MRSA Staff Infection
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sugar Pill L-serine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/9 (100.00%)      9/9 (100.00%)    
Gastrointestinal disorders     
ABDOMINAL PAIN UPPER   0/9 (0.00%)  0 1/9 (11.11%)  1
Diarrhea   1/9 (11.11%)  1 0/9 (0.00%)  0
Dyspepsia   0/9 (0.00%)  0 1/9 (11.11%)  1
Infections and infestations     
Cellulitis   1/9 (11.11%)  1 0/9 (0.00%)  0
Clostridium Difficile Infection   1/9 (11.11%)  1 0/9 (0.00%)  0
Influenza   1/9 (11.11%)  1 1/9 (11.11%)  1
Nail Infection   0/9 (0.00%)  0 1/9 (11.11%)  1
Nasopharyngitis   2/9 (22.22%)  2 2/9 (22.22%)  2
Osteomyelitis   0/9 (0.00%)  0 1/9 (11.11%)  2
Pneumonia   1/9 (11.11%)  1 0/9 (0.00%)  0
Sinusitis   1/9 (11.11%)  1 0/9 (0.00%)  0
Staphylococcal Infection   0/9 (0.00%)  0 1/9 (11.11%)  1
Localized Infection   1/9 (11.11%)  1 2/9 (22.22%)  2
Injury, poisoning and procedural complications     
Burns Second Degree   0/9 (0.00%)  0 1/9 (11.11%)  1
Foot Fracture   1/9 (11.11%)  1 1/9 (11.11%)  1
Frostbite   0/9 (0.00%)  0 1/9 (11.11%)  1
Tendon Injury   0/9 (0.00%)  0 1/9 (11.11%)  1
Thermal Burn   1/9 (11.11%)  1 0/9 (0.00%)  0
Investigations     
Blood Sodium Decreased   1/9 (11.11%)  1 0/9 (0.00%)  0
Metabolism and nutrition disorders     
Vitamin D Deficiency   0/9 (0.00%)  0 1/9 (11.11%)  1
Musculoskeletal and connective tissue disorders     
Bunion   0/9 (0.00%)  0 1/9 (11.11%)  1
Bursitis   1/9 (11.11%)  1 0/9 (0.00%)  0
Pain in Extremity   1/9 (11.11%)  1 1/9 (11.11%)  1
Tendonitis   1/9 (11.11%)  1 0/9 (0.00%)  0
Nervous system disorders     
Hypoaesthesia   0/9 (0.00%)  0 1/9 (11.11%)  1
Peripheral Sensory Neuropathy   1/9 (11.11%)  1 0/9 (0.00%)  0
Skin and subcutaneous tissue disorders     
Blister   0/9 (0.00%)  0 1/9 (11.11%)  1
Skin Ulcer   1/9 (11.11%)  2 1/9 (11.11%)  1
Surgical and medical procedures     
Finger Amputation   0/9 (0.00%)  0 1/9 (11.11%)  1
Vascular disorders     
Hypertension   1/9 (11.11%)  1 0/9 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Florian Eichler
Organization: Massachusetts General Hospital
Phone: 617-643-3799
EMail: Feichler@partners.org
Layout table for additonal information
Responsible Party: Florian Eichler, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01733407     History of Changes
Other Study ID Numbers: FD-R-04127-01
First Submitted: September 19, 2012
First Posted: November 27, 2012
Results First Submitted: May 3, 2018
Results First Posted: September 12, 2018
Last Update Posted: September 12, 2018