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

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.

Study Overview

• Status: Recruiting
• Conditions: Familial Hypercholesterolemia
• Intervention / Treatment: Drug: 2-Hydroxybenzylamine; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anca Ifrim, RN; Phone Number: 6155224210; Email: anca.ifrim@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals with heterozygous Familial Hypercholesterolemia.

Exclusion Criteria:

• 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,
• AIDS or HIV
• history of malignancy of any organ in last 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2-Hydroxybenzylamine (2-HOBA); 2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks.	Drug: 2-Hydroxybenzylamine; 2-Hydroxybenzylamine (2-HOBA) 250 mg three tabs TID (po) for 6 weeks.; Other Names: 2-HOBA
Placebo Comparator: Placebo; Placebo- three tabs TID (po) for 6 weeks.	Other: Placebo; Placebo 250 mg three tabs TID (po) for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG).	Measurement of the Iso-LG-lysine lactam by mass spectrometry.	Baseline to week 6
2-HOBA reduces modification of HDL by malondialdehyde (MDA).	Measurement of dilysyl-MDA cross-links by mass spectrometry.	Baseline to week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6).	Measurement of changes in LPS-stimulated 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.	Measurement of changes in H2O2-stimulated macrophage reactive oxygen species	Baseline to week 6
Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition	HDL microRNA and sRNA will be measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation.	Baseline to week 6
Effects of 2-HOBA on HDL and LDL subpopulation sizes	HDL and LDL subpopulation sizes and particle numbers will be measured by NMR	Baseline to week 6

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: MacRae F. Linton, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 18, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HDL; LDL; Familial Hypercholesterolemia; 2-HOBA; HDL Function
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; 2-(aminomethyl)phenol
• Other Study ID Numbers: 201575; 2P01HL116263-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported will be made available (including data dictionaries) after de-identification.
• IPD Sharing Time Frame: The data will become available 3 months following publication of outcomes and will remain available for at least 5 years.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No