Back to results

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

Primary Purpose

Familial Hypercholesterolemia

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

2-Hydroxybenzylamine

Placebo

About this trial

This is an interventional prevention trial for Familial Hypercholesterolemia focused on measuring Familial Hypercholesterolemia, HDL, LDL, 2-HOBA, HDL Function

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

2-Hydroxybenzylamine (2-HOBA)

Placebo

Arm Description

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

Placebo- three tabs TID (po) for 6 weeks.

Outcomes

Primary Outcome Measures

2-HOBA increases HDL cholesterol efflux capacity.

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).

Measurement of the Iso-LG-lysine lactam by mass spectrometry.

2-HOBA reduces modification of HDL by malondialdehyde (MDA).

Measurement of dilysyl-MDA cross-links by mass spectrometry.

Full Information

NCT ID

NCT04941599

First Posted

June 18, 2021

Last Updated

September 11, 2023

Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT04941599

Brief Title

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 2023 (Anticipated)

Primary Completion Date

July 2025 (Anticipated)

Study Completion Date

November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Familial Hypercholesterolemia

Keywords

Familial Hypercholesterolemia, HDL, LDL, 2-HOBA, HDL Function

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

2-Hydroxybenzylamine (2-HOBA)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo- three tabs TID (po) for 6 weeks.

Intervention Type

Drug

Intervention Name(s)

2-Hydroxybenzylamine

Other Intervention Name(s)

2-HOBA

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

2-HOBA increases HDL cholesterol efflux capacity.

Description

Change in HDL cholesterol efflux capacity will be measured by macrophage cholesterol efflux assay.

Time Frame

Baseline to week 6

Secondary Outcome Measure Information:

Title

2-HOBA reduces modification of HDL by Isolevuglandin (Iso-LG).

Description

Measurement of the Iso-LG-lysine lactam by mass spectrometry.

Time Frame

Baseline to week 6

Title

2-HOBA reduces modification of HDL by malondialdehyde (MDA).

Description

Measurement of dilysyl-MDA cross-links by mass spectrometry.

Time Frame

Baseline to week 6

Other Pre-specified Outcome Measures:

Title

Change in HDL anti-inflammatory function in an in vitro assay of macrophage cytokine production (IL-1B, TNFa, IL-6).

Description

Measurement of changes in LPS-stimulated macrophage cytokine production(IL-1B, TNFa, IL-6).

Time Frame

Baseline to week 6

Title

Change in HDL anti-oxidant function in an in vitro assay of macrophage reactive oxygen species production.

Description

Measurement of changes in H2O2-stimulated macrophage reactive oxygen species

Time Frame

Baseline to week 6

Title

Change in HDL microRNA and small noncoding ribonucleic acid (sRNA) composition

Description

HDL microRNA and sRNA will be measured through high-throughput sequencing with quantitative polymerase chain reaction (qPCR) validation.

Time Frame

Baseline to week 6

Title

Effects of 2-HOBA on HDL and LDL subpopulation sizes

Description

HDL and LDL subpopulation sizes and particle numbers will be measured by NMR

Time Frame

Baseline to week 6

Title

Effect of 2-HOBA on Endothelial Function as measured by Forearm Flow Mediated Dilatation.

Description

Noninvasive measure of endothelial function uses an ultrasound-based method to measure arterial diameter in response to an increase in shear stress.

Time Frame

Baseline to week 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

69 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Beth Meador, RN

Phone

6159361450

beth.meador@vumc.org

First Name & Middle Initial & Last Name or Official Title & Degree

Anca Ifrim, RN

Phone

6159361450

anca.ifrim@vumc.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MacRae F. Linton, MD

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37212

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs