2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)

NCT04941599 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2015752P01HL116263-06
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The Investigators will test the hypothesis that 2-HOBA will reduce modification of HDL and LDL and improve HDL function in humans with heterozygous FH. The Investigators plan to first study subjects with Familial Hypercholesterolemia (FH), treating them with 750 mg of 2-HOBA or placebo every 8 hours for 6 weeks.

Conditions

Familial Hypercholesterolemia

Keywords

Familial Hypercholesterolemia; HDL; LDL; 2-HOBA; HDL Function

Outcome Measures

Primary Outcomes (1)

• 2-HOBA increases HDL cholesterol efflux capacity.

  Change in HDL cholesterol efflux capacity will be measured by macrophage cholesterol efflux assay.

  Baseline to week 6

Secondary Outcomes (2)

• 2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG).

  Baseline to week 6

• 2-HOBA reduces modification of HDL by malondialdehyde (MDA).

  Baseline to week 6

Other Outcomes (4)

• Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6).

  Baseline to week 6

• Change in HDL anti-oxidant function in an in vitro assay of macrophage reactive oxygen species production.

  Baseline to week 6

• Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition

  Baseline to week 6

Study Arms (2)

2-Hydroxybenzylamine (2-HOBA)

ACTIVE COMPARATOR

2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks.

Drug: 2-Hydroxybenzylamine

Placebo

PLACEBO COMPARATOR

Placebo- three tabs TID (po) for 6 weeks.

Other: Placebo

Interventions

2-Hydroxybenzylamine DRUG

2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks.

Also known as: 2-HOBA

2-Hydroxybenzylamine (2-HOBA)

Placebo OTHER

Placebo 250 mg three tabs TID (po) for 6 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with heterozygous Familial Hypercholesterolemia.

You may not qualify if:

• Myocardial infarction or stroke within the last 6 months
• unstable angina, symptoms of angina within the last 3 months
• NYHA class III or IV heart failure or LVEF \< 30%
• poorly controlled hypertension: SBP \> 180 mm Hg or DBP \> 110 mm Hg,
• pregnancy,
• evidence of a previous acute coronary syndrome,
• current smokers,
• individuals with Type 2 Diabetes Mellitus, obesity (BMI \> 30),
• hypertriglyceridemia (fasting TG \> 250 mg/dl),
• renal insufficiency (Cr \> 1.8),
• hepatic disease (aspartate aminotransferase(AST) or alanine aminotransferase (ALT) \> 2x ULN),
• hypothyroidism,
• nephrotic syndrome,
• rheumatoid arthritis,
• systemic lupus erythematosus,

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Interventions

2-(aminomethyl)phenol

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• MacRae F. Linton, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anca Ifrim, RN

CONTACT

6155224210; anca.ifrim@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Pharmacology

Model Details: Subjects will be randomized to treatment with either 2-Hydroxybenzylamine (2-HOBA) , a naturally occuring dicarbonyl scavenger, or placebo for 6 weeks.

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: June 28, 2021
• Study Start: February 14, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.
• Access Criteria: Data will be made available to researchers who provide a methodologically sound proposal that has been approved by the Vanderbilt Institutional Review Board and the study executive committee.

Locations

US (1)