Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.
- 2019-01-22
- Neurology 92(4)
- Vera Fridman
- Saranya Suriyanarayanan
- Peter Novak
- William David
- Eric A Macklin
- Diane McKenna-Yasek
- Kailey Walsh
- Razina Aziz-Bose
- Anne Louise Oaklander
- Robert Brown
- Thorsten Hornemann
- Florian Eichler
- PubMed: 30626650
- DOI: 10.1212/wnl.0000000000006811
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 18
- Population
- patients aged 18-70 years with symptomatic HSAN1
- Methods
- randomized, placebo-controlled, parallel-group trial with open-label extension: l-serine (400 mg/kg/day) or placebo for 1 year, then all participants received l-serine during the second year
- Blinding
- Double-blind
- Duration
- 1 year
- Funding
- Unclear
Objective
To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1).Methods
In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events.Results
Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (-1.5 units, 95% CI -2.8 to -0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001). There were no serious adverse effects related to l-serine.Conclusion
High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression.Clinicaltrialsgov identifier
NCT01733407.Classification of evidence
This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.Research Insights
evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09)
- Effect
- Neutral
- Effect size
- Small
- Dose
- 400 mg/kg/day
Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001)
- Effect
- Beneficial
- Effect size
- Large
- Dose
- 400 mg/kg/day
Adverse Events Reported
There were no serious adverse effects related to l-serine.
- Finding
- Reported