Phase IIa L-serine Trial for eAD

Alzheimer Disease Clinical Trial

— LSPI-2  

Official title:

A Phase IIa Proof of Concept, Randomized, Double-blind, Placebo-controlled Study of the Effects of L-serine on Early Stage Alzheimer's Disease Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03062449
• Other study ID #: D16180
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 1, 2017
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2022
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase IIa, randomized, double-blind, placebo controlled trial. Subjects for participation in this study will be identified by the Investigator based on their Clinical Dementia Rating score which will be completed as part of standard practice. Patients meeting the criteria for early Alzheimer's disease will be considered for study participation, with the Investigator taking the additional inclusion/exclusion criteria into consideration. Up to 40 subjects will be enrolled. Subjects participating in the study will be randomized to receive either gummies containing L-Serine or placebo gummies, with the Investigator and study staff blinded to the group assignments.

Description:

L-serine (C3H7NO3; 105.09 g/mol; synonym (S)-2-amino-3-hydroxypropanoic acid) is a naturally-occurring dietary amino acid. It is abundant in soy products, some edible seaweeds, sweet potatoes, eggs, and meat. Since some L-serine is produced by astrocytes in the brain, it is considered a non-essential amino acid. L-serine is directly involved in the biosynthesis of purines, pyrimidines, and other amino acids. Serine residues are found in most proteins and within proteins function as a site for phosphorylation.

L-serine is considered as GRAS (generally recognized as safe) by the FDA and has been approved as a normal food additive under CFR172.320. It is widely sold as a dietary supplement. A pilot study of L-serine supplementation of 14 patients with hereditary sensory neuropathy has been published, and subsequent trial is on-going (ClinicalTrials.gov identifier NCT01733407). The authors did not report adverse effects at doses of 400mg/kg/day, which for an average American of 75.5kg is about 30 grams, the dose which we propose to use in this study.

L-serine will be administered orally through gummies being produced in a GMP compliant facility (Knechtel, Chicago, IL). Each gummy contains 1 g L-serine (treatment) and will be packaged in a foil packet containing 15 pieces to be taken both morning and evening for nine months. The placebo will be a gummy containing no L-serine, packaged and taken in the same manner. In order to assess tolerability in patients, we have designed a 4 week dose ramp-up. We will monitor side-effects and amino acid balances in blood samples in the early Alzheimer's Disease patients during a dose ramp-up period. If a patient cannot tolerate the full dose of gummies, they will remain in the study taking a total of 1 package of gummies split into two time periods within the day. The same ramp-up schedule and procedures will be observed for both placebo and L-serine patients. Patients will be assessed at baseline, 3 months, 6 months, and 9 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Diagnosis of early stage Alzheimer's disease as scored by the ClinicalDementia Rating Scale score of 0.5 -1.0 within the 6 months prior to study enrollment.

2. Participants able to provide informed consent.

3. Participants taking NMDA receptor antagonist medications or acetylcholinesterase inhibitor medications must be on a stable dose of these medications for at least 30 days prior to enrolling in this clinical trial.

4. Participants able to consume study gummy chews throughout the course of the clinical trial.

Exclusion Criteria:

1. Diagnosis or previous history of ischemic stroke, astrocytoma, meningioma or oligodendroma.

2. Diagnosis or previous history of any other comorbid diagnosis of neurodegenerative disease including amyotrophic lateral sclerosis, Parkinson's disease, Lewy Body Disease, Pick's Disease, Huntington's Disease, or Progressive Supra Nuclear Palsy.

3. Undergoing any chemotherapy or radiation therapy for any tumor or carcinoma.

4. Diagnosis or previous history of type I or type II diabetes. Potential subjects with no history of diabetes will be referred to their PCP for a hemoglobin A1C test if they have not had one in the year prior to enrollment.

5. Diagnosis or previous history of psychiatric illness that in the investigator's opinion would affect the subject's ability to successfully participate in the study.

6. In the Investigator's opinion, subject would be unable to successfully participate in the study for any reason.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• L-Serine
Gummy containing L serine dose

Other:
• Placebo Gummy
Gummy with no dosing of L Serine

Locations

Country	Name	City	State
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
Aleksandra Stark	Brain Chemistry Labs, Institute for Ethnomedicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in score on the Montreal Cognitive Assessment evaluation	Cognitive Assessment will be performed and score obtained at clinical trial visits	Baseline, 6 Months, 9 Months
Primary	Documentation of any adverse events	Each participant will report tolerability throughout the entirety of the study. Formal reports of tolerability will be taken at all trial visits and phone calls.	3 Months, 6 Months, 9 Months, and 12 Months
Primary	Changes in complete blood count, liver function test, basic metabolic panel measures.	Health check labs will be collected from every participant at each clinical trial visit.	Baseline, 3 Months, 6 Months, 9 months
Secondary	Change in plasma biomarker levels.	Levels of biomarkers related to cognitive status will be assessed in plasma that was collected at clinical trial visits.	Baseline, 6 Months, 9 months
Secondary	Relationship between Montreal Cognitive Assessment score and plasma biomarker levels	Disease status biomarker levels will be assessed in plasma at trial visits. Montreal Cognitive Assessment testing will be performed and scored at each visit.	Baseline, 6 Months, 9 months