A Phase 2 interventional study of L-Serine and Placebo Gummy in Alzheimer Disease, sponsored by Aleksandra Stark. Terminated at 1 site in United States. Per ClinicalTrials.gov, last updated 2024-07-03.
Sponsored by Aleksandra Stark · Phase 2, Interventional, and Treatment
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.
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. 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.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 29 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →This is the only study on the registry with Aleksandra Stark as lead sponsor.
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Exclusion Criteria:
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
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 containing L serine dose
Gummy with no dosing of L Serine
Change in Score on the Montreal Cognitive Assessment Assessment Evaluation
Cognitive Assessment will be performed and score obtained at clinical trial visits. The Montreal Cognitive Assessment or The MoCA Test is a highly sensitive tool for early detection of mild cognitive impairment. The assessment evaluates eight domains of cognitive functions, including visuospatial and executive function, naming, memory, attention, language, abstraction, and orientation. Scores on the MoCA range from 0 to 30. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
Time frame: Baseline, 6 Months, 9 Months
Change in Plasma Biomarker Levels.
Levels of biomarkers related to cognitive status will be assessed in plasma that was collected at clinical trial visits.
Time frame: Baseline, 6 Months, 9 months
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.
Time frame: Baseline, 6 Months, 9 months
Self-reported L-serine Tolerability
Each participant will report tolerability on a scale of 1 to 10 (1 = poor and 10 = excellent). This assessment was completed at the end of participation via a phone calls 4 weeks after visit 4.
Time frame: 4 weeks (+/- 2 weeks) after visit 4 (week 36 +/- 2 weeks)
Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures.
Health check labs will be collected from every participant at each clinical trial visit. clinically significant lab values will be identified for complete blood count, liver function test, and basic metabolic panel measures.
Time frame: Baseline, 3 Months, 6 Months, 9 months
The study was placed on voluntary hold by the institution prior to study completion. Upon review of the stability data of the investigational agent provided by the product's manufacturer, the FDA IND Sponsor-Investigator (PI) and institutional officials determined that the available information was unsatisfactory. No reportable study outcome data are available as determined by the institution and Sponsor-Investigator (PI) because the stability of the investigational product cannot be verified.
| Milestone | L-Serine Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| Started | 16 | 13 |
| Completed treatment | 10 | 12 |
| Completed | 9 | 12 |
| Not completed | 7 | 1 |
| Withdrew: Withdrawal by subject | 7 | 1 |
Cognitive Assessment will be performed and score obtained at clinical trial visits. The Montreal Cognitive Assessment or The MoCA Test is a highly sensitive tool for early detection of mild cognitive impairment. The assessment evaluates eight domains of cognitive functions, including visuospatial and executive function, naming, memory, attention, language, abstraction, and orientation. Scores on the MoCA range from 0 to 30. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
| score on a scale | L-Serine Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| Baseline | 20.625 (16 to 25) | 22.923 (14 to 30) |
| 6 Months | 19.846 (12 to 24) | 21.909 (15 to 28) |
| 9 Months | 20.3 (14 to 27) | 21.5 (13 to 29) |
Levels of biomarkers related to cognitive status will be assessed in plasma that was collected at clinical trial visits.
No measurements were reported for this outcome.
Disease status biomarker levels will be assessed in plasma at trial visits. Montreal Cognitive Assessment testing will be performed and scored at each visit.
No measurements were reported for this outcome.
Each participant will report tolerability on a scale of 1 to 10 (1 = poor and 10 = excellent). This assessment was completed at the end of participation via a phone calls 4 weeks after visit 4.
| units on a scale | L-Serine Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| Self-reported L-serine Tolerability | 8 (1 to 10) | 8 (1 to 10) |
Health check labs will be collected from every participant at each clinical trial visit. clinically significant lab values will be identified for complete blood count, liver function test, and basic metabolic panel measures.
| # of clinically significant lab values | L-Serine Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| Baseline | 0 | 0 |
| 3 Months | 0 | 0 |
| 6 Months | 0 | 0 |
| 9 Months | 0 | 0 |
Collected over Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by the Sponsor-Investigator (PI) and institutional officials. Study was closed by the PI and institution prior to study completion. Data are potentially invalid due to inadequate stability testing performed by the manufacturer; the sponsor-investigator is unable to confirm that investigational product remained stable overtime. Adverse event data were collected over approximately 4 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| L-Serine: Gummy Arm | 0/16 (0%) | 1/16 (6.3%) | 16/16 (100%) |
| Placebo Gummy Arm | 0/13 (0%) | 2/13 (15.4%) | 13/13 (100%) |
| Event | L-Serine: Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| gastroenteritisGastrointestinal disorders | 0/16 | 2/13 |
| chest painGeneral disorders | 1/16 | 0/13 |
| Event | L-Serine: Gummy Arm | Placebo Gummy Arm |
|---|---|---|
| cognitive declineNervous system disorders | 3/16 | 7/13 |
| diarrheaGastrointestinal disorders | 5/16 | 2/13 |
| skin lesion or rashInjury, poisoning and procedural complications | 4/16 | 1/13 |
| weight gainInvestigations | 3/16 | 3/13 |
| sleep disturbancePsychiatric disorders | 3/16 | 0/13 |
| weight lossInvestigations | 2/16 | 2/13 |
| cellulitisInfections and infestations | 0/16 | 2/13 |
| gasGastrointestinal disorders | 1/16 | 2/13 |
| irritabilityPsychiatric disorders | 2/16 | 2/13 |
| cataract extractionEye disorders | 2/16 | 1/13 |
All study participants are grouped for the baseline measure and reported for all participants collectively. The study was closed by the PI and institution prior to study completion because the stability of the investigational product could not be verified.
| Age, Categorical(Participants) | L-serine Gummy Arm | Placebo Gummy Arm | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 5 | 2 | 7 |
| >=65 years | 11 | 11 | 22 |
| Sex: Female, Male(Participants) | L-serine Gummy Arm | Placebo Gummy Arm | Total |
|---|---|---|---|
| Female | 8 | 6 | 14 |
| Male | 8 | 7 | 15 |
| Race (NIH/OMB)(Participants) | L-serine Gummy Arm | Placebo Gummy Arm | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 16 | 13 | 29 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | L-serine Gummy Arm | Placebo Gummy Arm | Total |
|---|---|---|---|
| United States | 16 | 13 | 29 |
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