Alzheimer DiseasePhase 2LSPI-2NCT03062449
Phase IIa L-serine Trial for eAD
A Phase 2 study testing L-Serine in people with Alzheimer Disease, run by Aleksandra Stark at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- L-Serine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2017to 20 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- Participants able to provide informed consent.
- 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.
- Participants able to consume study gummy chews throughout the course of the clinical trial.
Who cannot join
- Diagnosis or previous history of ischemic stroke, astrocytoma, meningioma or oligodendroma.
- 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.
- Undergoing any chemotherapy or radiation therapy for any tumor or carcinoma.
- 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.
- 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.
- In the Investigator's opinion, subject would be unable to successfully participate in the study for any reason.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
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
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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- L-Serine, Placebo Gummy
- Keywords
- L-Serine, Alzheimer's Disease, AD, Memory,
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-SerineDrug
Gummy containing L serine dose
Placebo GummyOther
Gummy with no dosing of L Serine
| Study group | Role | What they receive |
|---|---|---|
| L-Serine Gummy Arm | Active comparator | 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. Receives: Drug: L-Serine |
| Placebo Gummy Arm | Placebo comparator | 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. Receives: Other: Placebo Gummy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 6 Months, 9 Months
Secondary outcomes (2)
Change in Plasma Biomarker Levels.
Levels of biomarkers related to cognitive status will be assessed in plasma that was collected at clinical trial visits.
Measured: 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.
Measured: Baseline, 6 Months, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start1 Mar 2017
- Primary completion20 Jul 2021
- Study completion20 Jul 2021
Why it stopped: Stability of investigational product could not be established.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aleksandra Stark
- Sponsor type
- University, hospital or other
- Collaborators
- Brain Chemistry Labs
- Responsible party
- Sponsor-investigator, Aleksandra Stark, Dartmouth-Hitchcock Medical Center
- Investigators
- Aleksandra C Stark, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03062449
- Sponsor's protocol ID
- D16180
- Acronym
- LSPI-2
- Status last verified
- Jun 2024
- First submitted
- 20 Feb 2017
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03062449
- Acronym / sponsor ID
- LSPI-2 / D16180
- Conditions
- Alzheimer Disease
- Keywords
- L-Serine, Alzheimer's Disease, AD, Memory,
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stability of investigational product could not be established.
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Aleksandra StarkUniversity, hospital or other
- Collaborators
- Brain Chemistry Labs
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 20 Jul 2021 (actual)
- Study completion
- 20 Jul 2021 (actual)
- First posted
- 23 Feb 2017 (actual)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-Serine Gummy Arm | Active comparator | Drug: L-SerineL-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. |
| Placebo Gummy Arm | Placebo comparator | Other: Placebo GummyPlacebo 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- Participants able to provide informed consent.
- 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.
- Participants able to consume study gummy chews throughout the course of the clinical trial.
Key exclusion criteria (6 listed)
- Diagnosis or previous history of ischemic stroke, astrocytoma, meningioma or oligodendroma.
- 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.
- Undergoing any chemotherapy or radiation therapy for any tumor or carcinoma.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-SerineGummy containing L serine dose | Drug | L-Serine Gummy Arm |
| Placebo GummyGummy with no dosing of L Serine | Other | Placebo Gummy Arm |
Primary outcome
Change in Score on the Montreal Cognitive Assessment Assessment Evaluation
Time frame: 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.
2 secondary outcomes
Change in Plasma Biomarker Levels.
Time frame: Baseline, 6 Months, 9 months
Relationship Between Montreal Cognitive Assessment Score and Plasma Biomarker Levels
Time frame: Baseline, 6 Months, 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aleksandra C Stark, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-Serine in people with Alzheimer Disease, run by Aleksandra Stark at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Score on the Montreal Cognitive Assessment Assessment Evaluation (time frame: Baseline, 6 Months, 9 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.