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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: l-Histidine
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >49 years Live at home currently Clinical Dementia Score of 3.0 or higher Exclusion Criteria: psychiatric

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Control | Other: Control<br>* Control<br>|
| Active Comparator: Treatment-Histidine<br>Treatment-Histidine | Drug: l-Histidine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 months | 

Secondary Outcome Measures

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