Histidine Supplementation for Alzheimer's Disease

Overseen By Wells Reynolds, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Psychiatric

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether histidine, a natural compound, can help people with Alzheimer's disease improve memory and thinking skills. The researchers aim to determine if histidine increases certain brain chemicals linked to better cognition and reduces harmful proteins. Participants will be randomly assigned to take either histidine oral supplementation or a placebo (a pill with no active ingredient) for three months to compare results. It suits individuals over 49 who live at home and have significant memory problems. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for histidine oral supplementation?

Research shows that histidine, an important amino acid, plays several roles in the body. It balances acids and removes harmful molecules. Some studies have found that histidine supplements can improve memory test scores in people with Alzheimer's, suggesting potential benefits for thinking and memory problems.

However, safety remains crucial. Studies have found that high doses of histidine, about 15 grams, can cause many side effects. Approximately 77% of participants experienced issues, with headaches being the most common. While histidine might be helpful, the dosage is key to avoiding side effects. Adjusting the dose can make histidine a safer choice for those considering it. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Histidine oral supplementation is unique because it introduces a new approach to treating Alzheimer's disease by focusing on amino acid supplementation. Unlike traditional treatments that primarily target neurotransmitters or beta-amyloid plaques, histidine aims to support brain health through its role in protein synthesis and neurotransmitter production. Researchers are excited about this treatment because it could offer a more natural and potentially safer alternative to current medications, with fewer side effects and a different mechanism of action that addresses underlying nutritional deficiencies.

What evidence suggests that histidine supplementation might be an effective treatment for Alzheimer's?

Studies have shown that histidine supplements can improve memory and thinking skills in people with Alzheimer's disease. Specifically, one study found that histidine enhances performance on memory tests like the Delayed Recall test, which Alzheimer's often affects early. Research also suggests that histidine might slow memory and thinking problems by increasing levels of important brain chemicals. These chemicals can improve blood flow, help grow new brain cells, and remove harmful proteins linked to Alzheimer's. In this trial, participants will receive either histidine oral supplementation or a placebo. Overall, these promising findings suggest that histidine could help improve thinking skills in people with Alzheimer's. ^{1 2 4 6 7}

Who Is on the Research Team?

Wells Reynolds, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's Disease who are interested in testing whether a dietary supplement, l-Histidine, can improve their cognitive function. Participants will be randomly assigned to receive either the Histidine supplement or a placebo for three months.

Inclusion Criteria

Live at home currently

I am 50 years old or older.

Clinical Dementia Score of 3.0 or higher

Exclusion Criteria

Psychiatric

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either Histidine or placebo for up to 3 months, with titrated dosing of L-histidine in the treatment arm

3 months

Baseline evaluation, 3-month clinic visit

Follow-up

Participants are monitored for safety and effectiveness after treatment, with cognitive testing and lab evaluations

9 months

1-year clinic visit

What Are the Treatments Tested in This Trial?

Interventions

• Histidine Oral Supplementation

Trial Overview The study is examining if taking l-Histidine orally can boost brain health and cognition in Alzheimer's patients by increasing certain substances that may help blood flow and brain repair. Patients will take the supplement or placebo over three months with evaluations before and after.

How Is the Trial Designed?

Group I: Treatment-Histidine Active Control 1 Intervention

Treatment-Histidine

Group II: Control Placebo Group 1 Intervention

Control

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06169826

Study Details | NCT06169826 | Histidine Oral ... Oral supplementation of histidine in patients with cognitive dysfunction should increase brain anserine, carnosine and histamine levels which will result in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38013229/

Histidine-containing dipeptide supplementation improves ... HCD, supplementation improved scores on the Delayed recall examination, a neuropsychological test affected early in Alzheimer's disease.

3. clinicaltrials.eu clinicaltrials.eu/inn/histidine/

Histidine – Application in Therapy and Current Clinical ... This research aims to see if histidine can slow down cognitive decline or even improve cognitive function in Alzheimer's patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7724102/

Intake of Seven Essential Amino Acids Improves Cognitive ... Current findings suggested that ingestion of the seven essential amino acids led to improved attention and cognitive flexibility and psychosocial functioning.

5. clinicaltrials.eu clinicaltrials.eu/inn/l-histidine/

L-Histidine: A Promising Treatment for Alzheimer's Disease ... It's believed to increase levels of certain brain chemicals that may improve cognition and reduce fatigue. How is L-Histidine being used in the Alzheimer's ...

6. mdpi.com mdpi.com/2072-6643/17/13/2130

A Safety, Tolerability, Plasma and Brain Concentration Study At doses of 15 g, the frequency of adverse events became unacceptably high, with 77% of participants experiencing side effects, most commonly headache (43.5%), ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7146355/

Histidine in Health and Disease: Metabolism, Physiological ... L-histidine (HIS) is an essential amino acid with unique roles in proton buffering, metal ion chelation, scavenging of reactive oxygen and nitrogen species.