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Phase IIa L-serine Trial for eAD (LSPI-2)

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ClinicalTrials.gov Identifier: NCT03062449
Recruitment Status : Suspended (pausing enrollment while protocol changes are being made and submitted)
First Posted : February 23, 2017
Last Update Posted : October 4, 2018
Sponsor:
Collaborator:
Brain Chemistry Laboratories, Institute for Ethnomedicine
Information provided by (Responsible Party):
Aleksandra Stark, Dartmouth-Hitchcock Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: L-Serine Other: Placebo Gummy Phase 2

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : August 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Serine

Arm Intervention/treatment
Active Comparator: L-Serine Gummy Arm
L-serine will be presented in gummies containing 1g serine each. Subjects randomized into the L-serine arm will take 15 grams of L-Serine (15 gummies containing 1g of L-serine) orally twice daily for 246 days after the initial ascending dose period to confirm tolerability of the dose.
Drug: L-Serine
Gummy containing L serine dose

Placebo Comparator: Placebo Gummy Arm
Placebo gummies containing no L-serine will be packaged in the same manner as that of the L-Serine gummy arm and be given to patients to take two times a day.
Other: Placebo Gummy
Gummy with no dosing of L Serine




Primary Outcome Measures :
  1. Change in score on the Montreal Cognitive Assessment evaluation [ Time Frame: Baseline, 6 Months, 9 Months ]
    Cognitive Assessment will be performed and score obtained at clinical trial visits

  2. Documentation of any adverse events [ Time Frame: 3 Months, 6 Months, 9 Months, and 12 Months ]
    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. Changes in complete blood count, liver function test, basic metabolic panel measures. [ Time Frame: Baseline, 3 Months, 6 Months, 9 months ]
    Health check labs will be collected from every participant at each clinical trial visit.


Secondary Outcome Measures :
  1. Change in plasma biomarker levels. [ Time Frame: Baseline, 6 Months, 9 months ]
    Levels of biomarkers related to cognitive status will be assessed in plasma that was collected at clinical trial visits.

  2. Relationship between Montreal Cognitive Assessment score and plasma biomarker levels [ Time Frame: Baseline, 6 Months, 9 months ]
    Disease status biomarker levels will be assessed in plasma at trial visits. Montreal Cognitive Assessment testing will be performed and scored at each visit.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03062449


Locations
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Aleksandra Stark
Brain Chemistry Laboratories, Institute for Ethnomedicine
Investigators
Principal Investigator: Aleksandra C Stark, MD Dartmouth-Hitchcock Medical Center

Responsible Party: Aleksandra Stark, MD, Assistant Professor of Neurology, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT03062449     History of Changes
Other Study ID Numbers: D16180
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aleksandra Stark, Dartmouth-Hitchcock Medical Center:
L-Serine, Alzheimer's Disease, AD, Memory,

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders