Histidine Oral Supplementation as a Therapeutic Modality for Alzheimer's Disease

April 23, 2025 updated by: Wake Forest University Health Sciences

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Atrium Health Wake Forest Baptist

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • >49 years
  • Live at home currently
  • Clinical Dementia Score of 3.0 or higher

Exclusion Criteria:

  • psychiatric

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Other: Control
Control
Active Comparator: Treatment-Histidine
Drug: l-Histidine
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histidine blood levels
Time Frame: 3 months
the comparison in histidine and histamine levels between groups at baseline and 3 months.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Wells Reynolds, MD, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2025

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

December 4, 2023

First Submitted That Met QC Criteria

December 13, 2023

First Posted (Actual)

December 14, 2023

Study Record Updates

Last Update Posted (Actual)

April 27, 2025

Last Update Submitted That Met QC Criteria

April 23, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00093174

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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