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
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: L-Serine Other: Placebo Gummy||Phase 2|
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|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
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.
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
- 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
- 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.
- 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.
- 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.
- 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.
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
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Aleksandra C Stark, MD||Dartmouth-Hitchcock Medical Center|