2-HOBA for High Cholesterol

Overseen By Beth Meador, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Diabetes, Obesity, Hypertension, Smoking, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a treatment called 2-HOBA (2-Hydroxybenzylamine) can benefit individuals with high cholesterol due to Familial Hypercholesterolemia (FH). The researchers aim to determine if 2-HOBA can enhance the function of "good" cholesterol (HDL) and reduce the modification of both HDL and "bad" cholesterol (LDL). Participants will receive either 2-HOBA or a placebo for six weeks. Individuals with FH who have not recently experienced heart issues like a heart attack or stroke may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that 2-HOBA is likely to be safe for humans?

Research has shown that 2-Hydroxybenzylamine (2-HOBA) is safe and well-tolerated in people. One study found that doses up to 825 mg were easily handled by healthy participants. They experienced no serious side effects, and any mild ones were unrelated to the treatment. This suggests that 2-HOBA is a promising and safe option for those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high cholesterol?

Most treatments for high cholesterol, such as statins, work by blocking the enzyme HMG-CoA reductase to reduce cholesterol production in the liver. But 2-Hydroxybenzylamine (2-HOBA) works differently, targeting oxidative stress, which is a contributing factor to cholesterol buildup. Researchers are excited about 2-HOBA because it has a novel mechanism that could complement existing therapies and potentially reduce side effects associated with traditional cholesterol-lowering drugs. Additionally, by focusing on oxidative stress, 2-HOBA might offer broader cardiovascular benefits, making it a promising candidate in the fight against heart disease.

What evidence suggests that 2-HOBA might be an effective treatment for high cholesterol?

Research has shown that 2-Hydroxybenzylamine (2-HOBA), which participants in this trial may receive, might help treat familial hypercholesterolemia (FH), a condition characterized by high cholesterol levels. Studies in mice have found that 2-HOBA can improve the function of HDL, often called "good" cholesterol, which helps remove "bad" cholesterol from the body. By neutralizing harmful substances called dicarbonyls, 2-HOBA protects HDL from damage and may lower the risk of heart disease. Early results in humans suggest that 2-HOBA could help reduce changes in both HDL and LDL (low-density lipoprotein, or "bad" cholesterol), possibly leading to better cholesterol control. This promising evidence suggests that 2-HOBA might be a helpful treatment for people with FH. ^{1 6 7 8 9}

Who Is on the Research Team?

MacRae F. Linton, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with a genetic condition called heterozygous Familial Hypercholesterolemia (FH), which causes high cholesterol. It's not suitable for pregnant people, those with recent cancer, severe kidney or liver disease, uncontrolled hypertension, heart failure, recent heart attack or stroke, certain autoimmune diseases like lupus and rheumatoid arthritis, HIV/AIDS, hypothyroidism or if they are current smokers.

Inclusion Criteria

I have a genetic condition that causes high cholesterol.

I have a genetic condition that causes high cholesterol.

Exclusion Criteria

Your blood has high levels of triglycerides when you haven't eaten for a while.

I have been diagnosed with systemic lupus erythematosus.

I have Type 2 Diabetes and my BMI is over 30.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 750 mg of 2-HOBA or placebo every 8 hours for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 2-Hydroxybenzylamine
• Placebo

Trial Overview

The study is testing whether taking a compound called 2-Hydroxybenzylamine (2-HOBA) can improve the function of HDL ('good' cholesterol) in people with FH. Participants will receive either 750 mg of 2-HOBA or a placebo every eight hours for six weeks to see if there's any difference between the two groups.

How Is the Trial Designed?

Group I: 2-Hydroxybenzylamine (2-HOBA) Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 8 healthy male volunteers, the ACAT inhibitor CL 277,082 was well tolerated with no significant side effects, indicating a good safety profile for this drug.

However, the treatment did not significantly affect cholesterol absorption, sterol excretion rates, or plasma lipoprotein levels, suggesting that CL 277,082 may not effectively inhibit ACAT activity or lower cholesterol in humans at the tested dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans. Harris, WS., Dujovne, CA., von Bergmann, K., et al.[2019]

In a placebo-controlled, double-blind study across multiple centers, atorvastatin significantly reduced total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B in a dose-dependent manner.

The study reported no serious adverse events, indicating that atorvastatin is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of atorvastatin in primary hypercholesterolemia. Japan Cholesterol Lowering Atorvastatin Study (J-CLAS) Group. [2018]

Gemfibrozil, at a daily dose of 1200 mg, effectively reduces total serum cholesterol, triglycerides, and apo B levels while increasing HDL cholesterol in patients with hyperlipidemia, demonstrating its efficacy as a lipid-lowering agent.

Long-term studies indicate that gemfibrozil has a more significant impact on lowering triglycerides than cholesterol, has few side effects, and maintains its effectiveness over time, making it a promising option for managing lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperlipoproteinemia, atherosclerosis and gemfibrozil. Nash, DT.[2017]

In a 26-week trial involving 39 patients with primary hypercholesterolemia, atorvastatin 10 mg significantly reduced LDL cholesterol levels by 35%, while the placebo group saw no change.

Atorvastatin also lowered triglyceride levels by 21%, and the treatment was well tolerated with no significant side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The lipid-lowering effects of atorvastatin, a new HMG-CoA reductase inhibitor: results of a randomized, double-masked study. Heinonen, TM., Stein, E., Weiss, SR., et al.[2019]

In a double-blind crossover trial with 20 patients suffering from hyperlipidemia, the new aryloxy derivative (clinofibrate) significantly reduced total cholesterol by 11% and triglycerides by 48% compared to placebo, which showed no significant changes.

Clinofibrate was generally well tolerated, with only one patient experiencing moderate diarrhea and abdominal pain, leading to the withdrawal of the treatment as a precaution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of hyperlipidemia. Clinical experience with clinofibrate]. Avellone, G., Di Garbo, V., Strano, A.[2013]

Citations

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Scavenging of reactive dicarbonyls with 2 ... - PubMed

We investigate the impact of the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in Ldlr -/- mice, a model of FH.

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Trial | NCT04941599

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.

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Material Safety Data Sheet of 2-Hydroxybenzylamine

Use full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Refer to ...

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pmc.ncbi.nlm.nih.gov

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First-in-human study assessing safety, tolerability, and ...

Conclusions. 2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate ...

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2-Hydroxybenzylamine

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932-30-9 | 2-(Aminomethyl)phenol

2-(Aminomethyl)phenol. SDS. CAS No.932-30-9; Cat. No.CS-D1655; Purity≥98%; MDL ... Computational Chemistry Data; Safety Information; Quality Control. General ...