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

Tracking Information

• First Submitted Date: March 27, 2013
• First Posted Date: April 19, 2013
• Last Update Posted Date: July 30, 2015
• Study Start Date: January 2013
• Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 18, 2013)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: April 18, 2013): 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 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Determining the Safety of L-serine in ALS
• Official Title: Determining the Safety of L-Serine in Subjects With Amyotrophic Lateral Sclerois (ALS) at Varied Doses.
• 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.
• 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
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis (ALS)
• Intervention: Drug: L-Serine

Study Arms

• Active Comparator: 2.5 grams BID
  5 Patients will be evenly randomized into this group
  Intervention: Drug: L-Serine
• Active Comparator: .5 grams BID
  5 Patients will be evenly randomized into this group
  Intervention: Drug: L-Serine
• Active Comparator: 7.5 grams BID
  5 Patients will be evenly randomized into this group
  Intervention: Drug: L-Serine
• Active Comparator: 15 grams BID
  5 Patients will be evenly randomized into this group
  Intervention: Drug: L-Serine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 18, 2013): 20
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01835782
• Other Study ID Numbers: L-Serine2013; IND ( Other Identifier: 116871 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Phoenix Neurological Associates, LTD
• Study Sponsor: Phoenix Neurological Associates, LTD
• Collaborators: Institute for Ethnomedicine

Investigators

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

• PRS Account: Phoenix Neurological Associates, LTD
• Verification Date: July 2015