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withdrawn by the PI
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Control |
|
| Treatment-Histidine | Active Comparator | Treatment-Histidine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| l-Histidine | Drug | 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. |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Histidine blood levels | the comparison in histidine and histamine levels between groups at baseline and 3 months. | 3 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wells Reynolds, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Atrium Health Wake Forest Baptist | Winston-Salem | North Carolina | 27157 | United States |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D006639 | Histidine |
| ID | Term |
|---|---|
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000601 | Amino Acids, Essential |
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|
| Control | Other | Control |
|
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |