Trial Outcomes & Findings for L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1 (NCT NCT01733407)
NCT ID: NCT01733407
Last Updated: 2018-09-12
Results Overview
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
COMPLETED
PHASE1/PHASE2
18 participants
48 Weeks
2018-09-12
Participant Flow
Participant milestones
| Measure |
Sugar Pill
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
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 Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
7
|
9
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1
Baseline characteristics by cohort
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
49.9 years
STANDARD_DEVIATION 16.9 • n=5 Participants
|
45.8 years
STANDARD_DEVIATION 11.0 • n=7 Participants
|
47.8 years
STANDARD_DEVIATION 14.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Charcot-Marie-Tooth Neuropathy Score
|
24.6 scores on a scale
STANDARD_DEVIATION 7.0 • n=5 Participants
|
20.6 scores on a scale
STANDARD_DEVIATION 10.0 • n=7 Participants
|
22.6 scores on a scale
STANDARD_DEVIATION 8.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: 48 WeeksThe 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
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
Charcot Marie Tooth Neuropathy Score
|
25.67 scores on a scale
Standard Deviation 6.69
|
20.22 scores on a scale
Standard Deviation 10.10
|
SECONDARY outcome
Timeframe: 48 WeeksCounts of nerve fibers per unit area in skin biopsies
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
Intraepidermal Nerve Fiber Density (IENFD)
Upper Thigh
|
34.67 nerve fibers per micrometer^2
Standard Deviation 35.12
|
49.56 nerve fibers per micrometer^2
Standard Deviation 43.44
|
|
Intraepidermal Nerve Fiber Density (IENFD)
Lower Calf
|
0.89 nerve fibers per micrometer^2
Standard Deviation 2.67
|
13.89 nerve fibers per micrometer^2
Standard Deviation 24.10
|
SECONDARY outcome
Timeframe: 48 WeeksAutonomic 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).
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
Autonomic Function Testing (AFT) Composite Autonomic Severity Score (CASS)
|
3.56 scores on a scale
Standard Deviation 1.24
|
2.22 scores on a scale
Standard Deviation 1.64
|
SECONDARY outcome
Timeframe: 48 WeeksEvaluates the functioning of electrical conduction of the motor and sensory nerves of the human body.
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
Nerve Conduction Testing
Motor Right Median (Wrist) Amplitude
|
3.34 microvolts
Standard Error 4.52
|
4.21 microvolts
Standard Error 4.29
|
|
Nerve Conduction Testing
Motor Right Ulnar (Wrist) Amplitude
|
2.49 microvolts
Standard Error 3.60
|
4.37 microvolts
Standard Error 4.80
|
|
Nerve Conduction Testing
Sensory Right Superficial Peroneal Amplitude
|
0.00 microvolts
Standard Error 0.00
|
0.00 microvolts
Standard Error 0.00
|
|
Nerve Conduction Testing
Motor Right Peroneal EDB (Ankle) Amplitude
|
0.54 microvolts
Standard Error 1.52
|
0.24 microvolts
Standard Error 0.66
|
|
Nerve Conduction Testing
Motor Right Peroneal Tib (Below) Amplitude
|
0.29 microvolts
Standard Error 0.47
|
1.39 microvolts
Standard Error 2.15
|
|
Nerve Conduction Testing
Sensrory Right Median Amplitude
|
1.34 microvolts
Standard Error 4.03
|
5.51 microvolts
Standard Error 9.27
|
|
Nerve Conduction Testing
Sensory Right Antebrach Amplitude
|
2.31 microvolts
Standard Error 3.94
|
5.89 microvolts
Standard Error 9.54
|
|
Nerve Conduction Testing
Sensory Right Superficial Radial Amplitude
|
4.56 microvolts
Standard Error 10.17
|
10.84 microvolts
Standard Error 20.11
|
|
Nerve Conduction Testing
Sensory Right Sural Amplitude
|
0.52 microvolts
Standard Error 1.57
|
1.07 microvolts
Standard Error 2.61
|
SECONDARY outcome
Timeframe: 48 WeeksPlasma levels of the deoxysphingoid lipid 1-deoxy-sphinganine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
1-deoxy-sphinganine
|
0.338 micromole per liter
Standard Deviation 0.191
|
0.112 micromole per liter
Standard Deviation 0.042
|
SECONDARY outcome
Timeframe: 48 weeksPlasma levels of the deoxysphingoid lipid 1-deoxy-sphingosine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups
Outcome measures
| Measure |
Sugar Pill
n=9 Participants
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 Participants
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.
|
|---|---|---|
|
1-deoxy-sphingosine
|
0.698 micromole per liter
Standard Deviation 0.306
|
0.337 micromole per liter
Standard Deviation 0.132
|
Adverse Events
Sugar Pill
L-serine
Serious adverse events
| Measure |
Sugar Pill
n=9 participants at risk
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Esophageal Cancer
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
MRSA Staff Infection
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
Other adverse events
| Measure |
Sugar Pill
n=9 participants at risk
Placebo arm
placebo: 400mg/kg/d divided TID for year 1 only.
|
L-serine
n=9 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Infections and infestations
Cellulitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Clostridium Difficile Infection
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Influenza
|
11.1%
1/9 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
|
Infections and infestations
Nail Infection
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
22.2%
2/9 • Number of events 2
|
22.2%
2/9 • Number of events 2
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/9
|
11.1%
1/9 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Sinusitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Staphylococcal Infection
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Burns Second Degree
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Foot Fracture
|
11.1%
1/9 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Frostbite
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tendon Injury
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Injury, poisoning and procedural complications
Thermal Burn
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Investigations
Blood Sodium Decreased
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bunion
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
11.1%
1/9 • Number of events 1
|
11.1%
1/9 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin Ulcer
|
11.1%
1/9 • Number of events 2
|
11.1%
1/9 • Number of events 1
|
|
Surgical and medical procedures
Finger Amputation
|
0.00%
0/9
|
11.1%
1/9 • Number of events 1
|
|
Vascular disorders
Hypertension
|
11.1%
1/9 • Number of events 1
|
0.00%
0/9
|
|
Infections and infestations
Localized Infection
|
11.1%
1/9 • Number of events 1
|
22.2%
2/9 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place