2-HOBA: Multiple Dosing Study in Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to test how well people tolerate a new dietary ingredient called 2-HOBA and how it is metabolized in the body. 2-HOBA is a compound that occurs naturally in buckwheat seeds. This dietary ingredient has been used in animal studies, and single doses have been tolerated well when given to a small group of healthy people. In this study we will test how well people tolerate taking 2-HOBA over 2 weeks and how it is metabolized by the body.

Detailed Description
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Consenting volunteers between 55 and 79 years old with metabolic syndrome, including males, and post-menopausal females will be recruited for the study. Eighteen volunteers will be studied with a reasonable sampling of ethnicities from the Nashville area, and an effort will be made to recruit equal numbers of males and females. The study will be conducted by the Vanderbilt Clinical Research Center (CRC). Based upon single dose pharmacokinetics, two multiple dose regimens will be studied to determine the safety, accumulation kinetics, and pharmacodynamic effects of multiple daily doses administered over 2 weeks. A complete health history and physical examination will be conducted by a physician. An EKG, baseline blood and urine sample, and vital signs will be taken prior to supplement administration. A physician will oversee all clinical aspects of the study and will be responsible for all trial-related medical decisions. Additionally, DNA will be collected from the blood drawn and used to determine if there are any genetic differences in metabolism of 2-HOBA. Volunteers will be given 3 daily doses of either placebo or one of two levels of 2-HOBA to determine the safety, accumulation kinetics, and pharmacodynamic effects of the multiple dose administration over a 2 week period.

Official Title
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2-Hydroxybenzylamine: Multiple Dosing Study in Older Adults

Conditions
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Older Adults

Intervention / Treatment
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* Dietary Supplement: 2-HOBA
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals between 55 and 79 years old with metabolic syndrome Men and post-menopausal women. Exclusion Criteria: Inability to give informed consent; Diseases that could manifest symptoms or signs that would confound interpretation of the relationship between 2-HOBA action and potential adverse effects; Diseases that manifest current morbidity; Known cardiac disease, kidney disease, hepatic dysfunction, or diagnosed coronary artery disease; Cancer with potential terminal outcome or under treatment at the time of study; Severe hypertension (defined by systolic blood pressure equal or higher than 170 mm Hg), cardiac pacemaker, or oral anticoagulant use at the time of the study; and Individuals with diabetes requiring insulin treatment.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned in a blinded fashion to 2-HOBA or placebo. A computer-generated randomization sequence with a block of size 3 will be used to assign participants at the ratio of 1:2 (placebo:2-HOBA) at each dose level of the treatment. All participants receiving the lower dose regimen will be completed before enrolling participants in the higher dose group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Placebo<br>* Placebo Comparator<br>|
| Experimental: 2-HOBA Low Dose<br>2-Hydroxybenzylamine acetate: 500mg dose | Dietary Supplement: 2-HOBA<br>* 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate<br>* Other names: 2-Hydroxybenzylamine;|
| Experimental: 2-HOBA High Dose<br>2-Hydroxybenzylamine acetate: 750mg dose | Dietary Supplement: 2-HOBA<br>* 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate<br>* Other names: 2-Hydroxybenzylamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Dose Tolerability | Tolerability will be assessed through adverse event reporting compared with the placebo group (Comparison of number of AE in treated group to number of AE in placebo group). | 15 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of oxidative protein adducts in platelets | Oxidative protein adducts will be measured in blood platelets as an indication of efficacy (ng adducted protein/mg protein). | 15 Days | 
| Blood Pressure | Blood pressure will be measured as an indicator of efficacy against oxidative stress (mm Hg). | 15 Days | 
| Maximum Plasma Concentration (Cmax) | Cmax will be calculated from multiple timed plasma measurements (ng/ml). | Day 1 and Day 15 | 
| Area Under the Curve (AUC) | AUC will be calculated from multiple timed plasma measurements (h*ng/ml). | Day 1 and Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Dosage