Determining the Safety of L-serine in ALS

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

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

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: L-Serine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Associates
  • California
    • San Francisco, California, United States, 94115
      • Forbes Norris MDA/ALS Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-85
2. Male or Female
3. Clinically diagnosed with probable or definite ALS based on El Escorial criteria
4. ALSFRS-R > 25
5. Able to provide informed consent to and comply with all medical procedures

Exclusion Criteria:

1. Outside age range of 18-85
2. Subjects with forced vital capacity (FVC) below 60%
3. Evidence of any motor neuron disease for over 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Phoenix Neurological Associates, LTD
• Collaborators: Institute for Ethnomedicine

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: March 27, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 19, 2013

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: ALS; L-Serine; BMAA
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: L-Serine2013; IND (Other Identifier: 116871)