Determining the Safety of L-serine in ALS

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of L-Serine in subjects with Amyotrophic Lateral Sclerosis (ALS) at varied doses.

Detailed Description
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Previous studies into the Guamian ALS-Parkinson's Dementia complex has identified β-methylamino-L-alanine (BMAA), as a potential neurotoxin responsible for this disease. BMAA is a non-essential amino acid and is produced by a cyanobacterium which is present in all ecosystems. Subsequently several groups have identified high concentrations of BMAA in brain tissues of patients from North America and Europe with several neurodegenerative diseases including ALS, Parkinson's Disease and Alzheimer's Diseases. It has been hypothesized that chronic intake of BMAA in the diet leads to mis-incorporation of the amino acid into brain proteins, where it produces slow neuronal damage and recent evidence has shown that BMAA is mis-incorporated into proteins in neuronal cell lines via seryl tRNA synthetase, thereby producing protein mis-folding and protein aggregates, leading to cell death. It has been demonstrated in mammalian neuronal cell cultures that exogenous L-serine could prevent the BMAA neurotoxin from being mis-incorporated into proteins, thereby preventing cell death and that very high doses of L-serine may compete with the transport of a number of non-essential amino acids across the blood-brain barrier via the y+ transporter. These findings have led us to believe that high doses of L-serine could possibly stop the mis-incorporation of BMAA into brain proteins which in turn would slow or even abate the progression of ALS. This study will determine the safety of different doses of L-serine given to ALS subjects at 0.5 gm twice daily (BID), 2.5gm BID, 7.5g BID or 15 grams BID for six months.

Official Title
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Determining the Safety of L-Serine in Subjects With Amyotrophic Lateral Sclerois (ALS) at Varied Doses.

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Drug: L-Serine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-85 Male or Female Clinically diagnosed with probable or definite ALS based on El Escorial criteria ALSFRS-R > 25 Able to provide informed consent to and comply with all medical procedures Exclusion Criteria: Outside age range of 18-85 Subjects with forced vital capacity (FVC) below 60% Evidence of any motor neuron disease for over 3 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2.5 grams BID<br>5 Patients will be evenly randomized into this group | Drug: L-Serine<br> <br> |
| Active Comparator: .5 grams BID<br>5 Patients will be evenly randomized into this group | Drug: L-Serine<br> <br> |
| Active Comparator: 7.5 grams BID<br>5 Patients will be evenly randomized into this group | Drug: L-Serine<br> <br> |
| Active Comparator: 15 grams BID<br>5 Patients will be evenly randomized into this group | Drug: L-Serine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of L-Serine | Determining the safety of L-Serine given at 0.5 gm twice daily (BID), 2.5gm BID, 7.5g BID or 15 grams BID for six months by assessing the total number of adverse events (AE)during treatment | 1-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure levels of β-Methylamino-L-alanine (BMAA) in blood, urine and Cerebrospinal fluid (CSF) to determine if there is a decline in levels over the course of treatment |  | 1-6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, L-Serine, BMAA