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

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04941599

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

25.5

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Familial Hypercholesterolemia	Drug: 2-Hydroxybenzylamine Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Aug 15, 2022

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

2-HOBA increases HDL cholesterol efflux capacity. [Baseline to week 6]
Change in HDL cholesterol efflux capacity will be measured by macrophage cholesterol efflux assay.

Secondary Outcome Measures

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

Other Outcome Measures

Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6). [Baseline to week 6]
Measurement of changes in LPS-stimulated macrophage cytokine production(IL-1B, TNFa, IL-6).
Change in HDL anti-oxidant function in an in vitro assay of macrophage reactive oxygen species production. [Baseline to week 6]
Measurement of changes in H2O2-stimulated macrophage reactive oxygen species
Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition [Baseline to week 6]
HDL microRNA and sRNA will be measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation.
Effects of 2-HOBA on HDL and LDL subpopulation sizes [Baseline to week 6]
HDL and LDL subpopulation sizes and particle numbers will be measured by NMR
Effect of 2-HOBA on Endothelial Function as measured by Forearm Flow Mediated Dilatation. [Baseline to week 6]
Noninvasive measure of endothelial function uses an ultrasound-based method to measure arterial diameter in response to an increase in shear stress.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.