Phase 2
N=18
L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1
Hereditary Sensory and Autonomic Neuropathy Type I
Bottom Line
View on ClinicalTrials.gov: NCT01733407 ↗Enrolled (actual)
18
Serious AEs
11.1%
Results posted
Sep 2018
Primary outcome: Primary: Charcot Marie Tooth Neuropathy Score — 25.67; 20.22 scores on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- L-serine (Drug); placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Massachusetts General Hospital
- Primary completion
- May 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Charcot Marie Tooth Neuropathy Score |
25.67; 20.22 | — |
| SECONDARY Intraepidermal Nerve Fiber Density (IENFD) |
34.67; 49.56; 0.89; 13.89 | — |
| SECONDARY Autonomic Function Testing (AFT) Composite Autonomic Severity Score (CASS) |
3.56; 2.22 | — |
| SECONDARY Nerve Conduction Testing |
1.34; 5.51; 2.31; 5.89; 4.56; 10.84 | — |
| SECONDARY 1-deoxy-sphinganine |
0.338; 0.112 | — |
| SECONDARY 1-deoxy-sphingosine |
0.698; 0.337 | — |
Summary
In hereditary sensory and autonomic neuropathy type 1 (HSAN1) the investigators recently discovered the accumulation of two neurotoxic sphingolipids. It appears that these lipids arise as the mutant enzyme has a reduced affinity for its normal preferred substrate L-serine. The investigators now plan to perform a two year study of L-serine supplementation to correct the biochemistry and neurological disease in humans with HSAN1. In the course the investigators will also establish correlations between an existing neurological rating scale of sensory neuropathy and intraepidermal nerve fiber density.
Funding Source - FDA OOPD
Eligibility Criteria
Inclusion Criteria
- HSAN1 patients with prominent sensory loss with foot ulcers or shooting pains and con-firmed mutations in SPTLC1.
- Males and females of 18 years or older
- All patients will be able to provide informed consent and comply with oral dietary supple-mentation and study activities. Compliance with supplementation will be monitored through measurement of DSB levels.
- Subjects must not have taken L-serine for at least 30 days prior to randomization (L-serine-naïve subjects are permitted in the study).
- Women must not become pregnant for the duration of the study and must be willing to use two contraceptive therapies and have a negative pregnancy test throughout the course of the study.
Exclusion Criteria
- Any cause of neuropathy other than HSAN1 (such as diabetes or drug-induced neuropathy), medical history of kidney stones, or history of poliomyelitis or radiotherapy.
- Pregnant women, breastfeeding, or not using adequate contraception; for women included, an accepted method of contraception will be used throughout the study.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Patients on blood-thinners such as warfarin (Coumadin) or heparin will not be biopsied until they have held the medication for 5 days. Following the biopsy they will resume the maintenance dose of their medication.
- Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 10 days prior to study entry.
- The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to PI judgment, or a history of active substance abuse within the prior year.
- Subjects who are non-ambulatory.
- Subjects with uncontrolled diabetes.
- Patients who are unable or unwilling to give consent will not be enrolled in the study.
Data sourced from ClinicalTrials.gov (NCT01733407). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.