Clinical trial NCT04941599: 2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
Official title: 2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Familial Hypercholesterolemia
Keywords: Familial Hypercholesterolemia
HDL
LDL
2-HOBA
HDL Function
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-06-28
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized to treatment with either 2-Hydroxybenzylamine (2-HOBA) , a naturally occuring dicarbonyl scavenger, or placebo for 6 weeks.
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 2-HOBA increases HDL cholesterol efflux capacity.
timeFrame: Baseline to week 6
Secondary outcomes:
measure: 2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG).
timeFrame: Baseline to week 6
measure: 2-HOBA reduces modification of HDL by malondialdehyde (MDA).
timeFrame: Baseline to week 6
Other outcomes:
measure: Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6).
timeFrame: Baseline to week 6
measure: Change in HDL anti-oxidant function in an in vitro assay of macrophage reactive oxygen species production.
timeFrame: Baseline to week 6
measure: Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition
timeFrame: Baseline to week 6
measure: Effects of 2-HOBA on HDL and LDL subpopulation sizes
timeFrame: Baseline to week 6
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: MacRae F. Linton, MD
role: PRINCIPAL_INVESTIGATOR
References: