Determining the Safety of L-serine in ALS

• ClinicalTrials.gov Identifier: NCT01835782
• Recruitment Status: Unknown
• First Posted: April 19, 2013
• Last Update Posted: July 30, 2015
• Sponsor: Phoenix Neurological Associates, LTD
• Collaborator: Institute for Ethnomedicine
• Information provided by (Responsible Party): Phoenix Neurological Associates, LTD

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: L-Serine	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Determining the Safety of L-Serine in Subjects With Amyotrophic Lateral Sclerois (ALS) at Varied Doses.
• Study Start Date: January 2013
• Estimated Primary Completion Date: December 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety of L-Serine [ Time Frame: 1-6 months ]
   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

Secondary Outcome Measures :

1. 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 [ Time Frame: 1-6 months ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Phoenix Neurological Associates

Phoenix, Arizona, United States, 85018

United States, California

Forbes Norris MDA/ALS Research Center

San Francisco, California, United States, 94115

Sponsors and Collaborators

Phoenix Neurological Associates, LTD

Institute for Ethnomedicine

Investigators

• Principal Investigator: Todd D Levine, MD; Phoenix Neurological Associates, LTD

More Information

• Responsible Party: Phoenix Neurological Associates, LTD
• ClinicalTrials.gov Identifier: NCT01835782
• Other Study ID Numbers: L-Serine2013; IND ( Other Identifier: 116871 )
• First Posted: April 19, 2013
• Last Update Posted: July 30, 2015
• Last Verified: July 2015

Keywords provided by Phoenix Neurological Associates, LTD:

ALS; L-Serine; BMAA

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases