2-HOBA: Initial Evaluation in Humans

Consenting volunteers of at least 18 years old with no morbidity, including males, and females who are not pregnant will be recruited for the study. A maximum of 28 volunteers may be enrolled with a reasonable sampling of ethnicities from the Nashville area, and an effort will be made to recruit equal numbers of males and females. Additionally, an effort will be made to study as old a population as possible and to recruit relatively similar age groups for males and females. All volunteers will be admitted to the Vanderbilt Clinical Research Center (CRC) as inpatients.

A complete health history and physical examination will be conducted by a physician. Volunteers will be asked to collect and bring their first morning voided urine for baseline urinalysis. An EKG, baseline blood analysis, vital signs, and questions about feelings and adverse events will be asked prior to supplement administration. All tests will be repeated at various intervals throughout the 24-hour study period. A physician will oversee all clinical aspects of the study and will be responsible for all trial-related medical decisions. Pharmacokinetics will be studied through the blood analyses at intervals throughout the study and 24-hour urine collection after administration of the supplement.

• 2-HOBA (Dietary supplement), also known as 2-Hydroxylbenzylamine: 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate

Primary outcomes

• Dose Tolerability [24 hours]: Tolerability will be assessed by occurrence of Adverse Events (AEs). If AEs occur in 2 out of 6 volunteers, the dose will be declared not tolerated and the previous dose with no AEs will be declared maximum tolerable dose. AEs < 2: dose is tolerated AEs ≥ 2: dose is not tolerated

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* Healthy individuals older than 18;
* Males and females who are not pregnant at the time of the study; and
* Not taking any medication 2 weeks prior to and during the study.

Exclusion Criteria:

* Inability to give informed consent;
* Diseases that could manifest symptoms or signs that would confound interpretation of the relation between drug action and potential adverse effects;
* Diseases that could manifest morbidity;
* Known cardiac disease, kidney disease, or hepatic dysfunction;
* The need to discontinue any drug that is administered as standard of care treatment; and
* Unwillingness or inability to use approved birth-control methods.

• Results publication: Pitchford LM, Rathmacher JA, Fuller JC Jr, Daniels JS, Morrison RD, Akers WS, Abumrad NN, Amarnath V, Currey PM, Roberts LJ, Oates JA, Boutaud O. First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers. BMC Pharmacol Toxicol. 2019 Jan 5;20(1):1. doi: 10.1186/s40360-018-0281-7. PMID 30611293

• John A Rathmacher, PhD, Principal investigator, Metabolic Technologies Inc.

NIH grants: R44AG055184