Alzheimer Disease
Conditions
Keywords
L-Serine, Alzheimer's Disease, AD, Memory,
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.
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. 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.
Interventions
DRUGL-Serine
Gummy containing L serine dose
OTHERPlacebo Gummy
Gummy with no dosing of L Serine
Sponsors
Brain Chemistry Labs
Aleksandra Stark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | Baseline, 6 Months, 9 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Biomarker Levels. | 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Self-reported L-serine Tolerability | 4 weeks (+/- 2 weeks) after visit 4 (week 36 +/- 2 weeks) | 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. |
| Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | Baseline, 3 Months, 6 Months, 9 months | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
Study participants are grouped for the participant flow. The study was closed by the Sponsor-Investigator and institution prior to study completion because the stability of the investigational product could not be verified.
Participants by arm
| Arm | Count |
|---|---|
| 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.
L-Serine: Gummy containing L serine dose | 16 |
| 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.
Placebo Gummy: Gummy with no dosing of L Serine | 13 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 7 | 1 |
Baseline characteristics
| Characteristic | L-serine Gummy Arm | Placebo Gummy Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 11 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 13 Participants | 29 Participants |
| Region of Enrollment United States | 16 participants | 13 participants | 29 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 13 |
| other Total, other adverse events | 16 / 16 | 13 / 13 |
| serious Total, serious adverse events | 1 / 16 | 2 / 13 |
Outcome results
Primary
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
Population: Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by the Sponsor-Investigator (PI) and institutional officials. The study was closed by the PI and institution prior to study completion. Data are potentially invalid due to the inadequate stability testing performed by the manufacturer, as the sponsor-investigator is unable to confirm that the investigational product remained stable over time. No reportable study outcome data are available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| L-Serine Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | Baseline | 20.625 score on a scale |
| L-Serine Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | 6 Months | 19.846 score on a scale |
| L-Serine Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | 9 Months | 20.3 score on a scale |
| Placebo Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | Baseline | 22.923 score on a scale |
| Placebo Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | 6 Months | 21.909 score on a scale |
| Placebo Gummy Arm | Change in Score on the Montreal Cognitive Assessment Assessment Evaluation | 9 Months | 21.5 score on a scale |
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.
Time frame: Baseline, 6 Months, 9 months
Population: Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by the Sponsor-Investigator (PI) and institutional officials. The study was closed by the PI and institution prior to study completion. Data are potentially invalid due to the inadequate stability testing performed by the manufacturer, as the sponsor-investigator is unable to confirm that the investigational product remained stable over time. The biomarker data does not exist.
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.
Time frame: Baseline, 6 Months, 9 months
Population: Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by the Sponsor-Investigator (PI) and institutional officials. The study was closed by the PI and institution prior to study completion. Data are potentially invalid due to the inadequate stability testing performed by the manufacturer, as the sponsor-investigator is unable to confirm that the investigational product remained stable over time. The biomarker data does not exist.
Other Pre-specified
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
Population: Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by the Sponsor-Investigator (PI) and institutional officials. Data are potentially invalid due to the inadequate stability testing performed by the manufacturer, as the sponsor-investigator is unable to confirm that the investigational product remained stable over time. The number of participants analyzed decreased over time due to participants withdrawing or being withdrawn by the PI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| L-Serine Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | Baseline | 0 # of clinically significant lab values |
| L-Serine Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 6 Months | 0 # of clinically significant lab values |
| L-Serine Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 3 Months | 0 # of clinically significant lab values |
| L-Serine Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 9 Months | 0 # of clinically significant lab values |
| Placebo Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 9 Months | 0 # of clinically significant lab values |
| Placebo Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | Baseline | 0 # of clinically significant lab values |
| Placebo Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 3 Months | 0 # of clinically significant lab values |
| Placebo Gummy Arm | Number of Clinically Significant Lab Values for Complete Blood Count, Liver Function Test, Basic Metabolic Panel Measures. | 6 Months | 0 # of clinically significant lab values |
Other Pre-specified
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)
Population: Investigational agent stability data provided by product's manufacturer was determined to be unsatisfactory by Sponsor-Investigator (PI) and institutional officials. The study was closed by PI and institution prior to study completion. Data are potentially invalid due to inadequate stability testing performed by the manufacturer, as PI is unable to confirm that investigational product remained stable over time. Only 10 participants from L-serine and 7 from placebo group completed the assessment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| L-Serine Gummy Arm | Self-reported L-serine Tolerability | 8 units on a scale |
| Placebo Gummy Arm | Self-reported L-serine Tolerability | 8 units on a scale |