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

Familial Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04941599
• Other study ID #: 201575
• Secondary ID: 2P01HL116263-06
• Status: Recruiting
• Phase: Phase 2
• Start date: February 14, 2024
• Est. completion date: November 2025

Study information

• Verified date: February 2024
• Source: Vanderbilt University Medical Center
• Contact: Anca Ifrim, RN
• Phone: 6155224210
• Email: anca.ifrim[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: November 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

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

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

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	Effect of 2-HOBA on Endothelial Function as measured by Forearm Flow Mediated Dilatation.	Noninvasive measure of endothelial function uses an ultrasound-based method to measure arterial diameter in response to an increase in shear stress.	Baseline to week 6
Primary	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	2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG).	Measurement of the Iso-LG-lysine lactam by mass spectrometry.	Baseline to week 6
Secondary	2-HOBA reduces modification of HDL by malondialdehyde (MDA).	Measurement of dilysyl-MDA cross-links by mass spectrometry.	Baseline to week 6