2-HOBA: Initial Evaluation in Humans (2-HOBA)

2-Hydroxybenzylamine: Initial Evaluation in Humans

The purpose of this study is to evaluate the administration of single doses of 2-HOBA in humans, with an escalation of doses that begins with the calculated Maximum Recommended Starting Dose. This evaluation will assess tolerability to oral administration of 2-HOBA, obtain pharmacokinetic data, characterize the 2-HOBA metabolic pathways, and determine the relation of dose to prevention of formation of bi-functional electrophile adducts in blood. Characterization of the metabolic fate of 2-HOBA will be supported by investigations that evaluate metabolism in microsomes and cells.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Dietary supplement: 2-HOBA

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2-HOBA first dose; Dose escalation studies in humans: 50mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine
Experimental: 2-HOBA second dose; Dose escalation studies in humans: 100mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine
Experimental: 2-HOBA third dose; Dose escalation studies in humans: 200mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine
Experimental: 2-HOBA fourth dose; Dose escalation studies in humans: 330mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine
Experimental: 2-HOBA fifth dose; Dose escalation studies in humans: 550mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine
Experimental: 2-HOBA sixth dose; Dose escalation studies in humans: 825mg dose	Dietary supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Names: 2-Hydroxylbenzylamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Tolerability	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	24 hours

Collaborators and Investigators

• Sponsor: Metabolic Technologies Inc.
• Collaborators: National Institute on Aging (NIA); Vanderbilt University
• Investigators: Principal Investigator: John A Rathmacher, PhD, Metabolic Technologies Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2017
• Primary Completion (Actual): March 31, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): June 4, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Escalating Dosage
• Other Study ID Numbers: 161861; R44AG055184 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No