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

Study Overview
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Brief Summary
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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.

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

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: 2-Hydroxybenzylamine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial Hypercholesterolemia, HDL, LDL, 2-HOBA, HDL Function