Alzheimer DiseasePhase 4NCT06169826
Histidine Oral Supplementation as a Therapeutic Modality for Alzheimer's Disease
A Phase 4 study testing l-Histidine in people with Alzheimer Disease, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
Oral supplementation of histidine in patients with cognitive dysfunction should increase brain anserine, carnosine and histamine levels which will result in improved cognition via numerous proven in vivo mechanisms including increasing blood flow, neurogenesis, angiogenesis, activation of histaminergic neural pathways… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- l-Histidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2025to Apr 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >49 years
- Live at home currently
- Clinical Dementia Score of 3.0 or higher
Who cannot join
- psychiatric
Trial locations and contacts
1 site in 1 country.
United States1 site
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
About this study
Oral supplementation of histidine in patients with cognitive dysfunction should increase brain anserine, carnosine and histamine levels which will result in improved cognition via numerous proven in vivo mechanisms including increasing blood flow, neurogenesis, angiogenesis, activation of histaminergic neural pathways and autophagy of beta-amyloid protein, which is pathognomonic for Alzheimer's disease.
Randomized into one of 2 arms to receive Histidine or placebo to take for up to 3 months. Baseline evaluation and followup evaluation at 3 months postop.
Read the detailed description
The patients will be offered enrollment by sequential measures with odd numbers placed into the Control Group and even numbers in the Treatment Arm. One hundred patients will be enrolled in each arm. Study medications will be initiated in the outpatient setting following informed consent, enrollment and baseline lab evaluation. Scheduled clinic visits at 3 months and 1 year from date of enrollment will be used to re-assess performance via repeat cognitive testing. Lab evaluation of CBC, CMP, histidine and histamine levels will occur at baseline and the 3 month clinic visit for the treatment arm subjects.
Group I: Control Arm- No intervention. Subjects will receive cognitive and lab testing and continue with current management of their cognitive impairment.
Group II: Treatment Arm- In the outpatient setting, one chewable tablet multivitamin (Zn and folic acid containing) plus a titrated dosing of L-histidine powder or capsules starting at 2g consumed before noon escalating every 2 weeks up to 4, 6, then 8 g per day as tolerated.
- Conditions
- Alzheimer Disease
- Being tested
- l-Histidine, Control
- 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-HistidineDrug
In the outpatient setting, one chewable tablet multivitamin (Zn and folic acid containing) plus a titrated dosing of L-histidine powder or capsules starting at 2g consumed before noon escalating every 2 weeks up to 4, 6, then 8 g per day as tolerated for up to 3 months.
ControlOther
Control
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Control Receives: Other: Control |
| Treatment-Histidine | Active comparator | Treatment-Histidine Receives: Drug: l-Histidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Dementia Rating
The median change in the score at 12 months on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment) between groups looking for regression to higher levels of cognition or conversion to more severe dementia
Measured: 12 months
Secondary outcomes (1)
Histidine blood levels
the comparison in histidine and histamine levels between groups at baseline and 3 months.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2023
- Study startApr 2025 (estimated)
- Primary completionApr 2026 (estimated)
- Study completionApr 2026 (estimated)
Why it stopped: withdrawn by the PI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wells Reynolds, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06169826
- Sponsor's protocol ID
- IRB00093174
- Status last verified
- Dec 2024
- First submitted
- 4 Dec 2023
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histidine Oral Supplementation as a Therapeutic Modality for Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06169826
- Acronym / sponsor ID
- IRB00093174
- Conditions
- Alzheimer Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: withdrawn by the PI
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Apr 2025 (estimated)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 14 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Oral supplementation of histidine in patients with cognitive dysfunction should increase brain anserine, carnosine and histamine levels which will result in improved cognition via numerous proven in vivo mechanisms including increasing blood flow, neurogenesis, angiogenesis, activation of histaminergic neural pathways and autophagy of beta-amyloid protein, which is pathognomonic for Alzheimer's disease.
Randomized into one of 2 arms to receive Histidine or placebo to take for up to 3 months. Baseline evaluation and followup evaluation at 3 months postop.
Detailed description
The patients will be offered enrollment by sequential measures with odd numbers placed into the Control Group and even numbers in the Treatment Arm. One hundred patients will be enrolled in each arm. Study medications will be initiated in the outpatient setting following informed consent, enrollment and baseline lab evaluation. Scheduled clinic visits at 3 months and 1 year from date of enrollment will be used to re-assess performance via repeat cognitive testing. Lab evaluation of CBC, CMP, histidine and histamine levels will occur at baseline and the 3 month clinic visit for the treatment arm subjects.
Group I: Control Arm- No intervention. Subjects will receive cognitive and lab testing and continue with current management of their cognitive impairment.
Group II: Treatment Arm- In the outpatient setting, one chewable tablet multivitamin (Zn and folic acid containing) plus a titrated dosing of L-histidine powder or capsules starting at 2g consumed before noon escalating every 2 weeks up to 4, 6, then 8 g per day as tolerated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Other: ControlControl |
| Treatment-Histidine | Active comparator | Drug: l-HistidineTreatment-Histidine |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- >49 years
- Live at home currently
- Clinical Dementia Score of 3.0 or higher
Key exclusion criteria (1 listed)
- psychiatric
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-HistidineIn the outpatient setting, one chewable tablet multivitamin (Zn and folic acid containing) plus a titrated dosing of L-histidine powder or capsules starting at 2g consumed before noon escalating every 2 weeks up to 4, 6, then 8 g per day as tolerated for up to 3 months. | Drug | Treatment-Histidine |
| ControlControl | Other | Control |
Primary outcome
Clinical Dementia Rating
Time frame: 12 months
The median change in the score at 12 months on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment) between groups looking for regression to higher levels of cognition or conversion to more severe dementia
1 secondary outcome
Histidine blood levels
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
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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.
Wells Reynolds, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing l-Histidine in people with Alzheimer Disease, run by Wake Forest University Health Sciences 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 3 inclusion and 1 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: withdrawn, as of the sponsor's last update on 27 Apr 2025. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Clinical Dementia Rating (time frame: 12 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 27 Apr 2025.