2-HOBA for Alzheimer's Disease

(2-HOBA Trial)

Overseen By John A. Rathmacher, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: MTI Biotech Inc

Must be taking: Memantine, Cholinesterase inhibitors

Must not be taking: Centrally acting anticholinergics, Investigational drugs

Disqualifiers: Parkinson's, Schizophrenia, Uncontrolled diabetes, others

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new treatment, 2-Hydroxybenzylamine (2-HOBA), for individuals with mild cognitive impairment or mild Alzheimer's disease. Researchers aim to compare different doses of 2-HOBA to a placebo in affecting specific biological markers linked to Alzheimer's. Individuals who have noticed memory issues, either personally or through someone close, and have a diagnosis of mild cognitive or Alzheimer's-related symptoms might be suitable for this study. Participants will take either the 2-HOBA treatment or a placebo for 16 weeks, during which researchers will collect blood and spinal fluid samples to monitor changes. As a Phase 1, Phase 2 trial, this study seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial requires that certain medications be stable for at least 4 weeks before joining, and memantine and cholinesterase inhibitors must be stable for 12 weeks. Some medications, like centrally acting anti-cholinergic drugs, are not allowed. Please check with the trial team for specific guidance on your medications.

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

Research has shown that 2-Hydroxybenzylamine (2-HOBA) is generally safe for people. In one study, participants took up to 825 mg of 2-HOBA, and they tolerated it well. Another study found that taking up to 750 mg three times a day for 15 days was safe. Most side effects were mild and not directly related to the drug. No evidence indicates that 2-HOBA harms cells or causes genetic changes. Overall, current research suggests that this treatment is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Researchers are excited about 2-Hydroxybenzylamine (2-HOBA) for Alzheimer's because it offers a fresh approach compared to traditional treatments like cholinesterase inhibitors and NMDA receptor antagonists. Unlike these standard options, which primarily aim to manage symptoms, 2-HOBA works by scavenging reactive carbonyl species, which are harmful compounds that can damage brain cells. This novel mechanism targets a root cause of cellular damage in Alzheimer's, potentially slowing the disease's progression rather than just alleviating symptoms. With different doses being tested, researchers are keen to see how effective 2-HOBA can be in improving cognitive health.

What evidence suggests that 2-HOBA might be an effective treatment for Alzheimer's?

Research suggests that 2-Hydroxybenzylamine (2-HOBA) could help in treating Alzheimer's disease. Studies have shown that 2-HOBA quickly reacts with harmful substances in the brain, protecting important proteins from damage. This reaction occurs 1,600 times faster than a similar process with another compound, lysine, in both lab and animal studies. 2-HOBA is considered safe and well-tolerated in healthy people at doses up to 825 mg. These findings suggest that 2-HOBA might slow the early stages of Alzheimer's disease by protecting brain cells from harm. Participants in this trial will receive either a placebo or varying doses of 2-HOBA acetate to evaluate its effectiveness and safety in treating Alzheimer's disease. ^{1 2 4 5 6}

Who Is on the Research Team?

Paul A Newhouse, M.D.

Principal Investigator

Vanderbilt University Medical Center

John A. Rathmacher, Ph.D.

Principal Investigator

MTI Biotech Inc

Are You a Good Fit for This Trial?

This trial is for individuals with early Alzheimer's or mild cognitive impairment. Participants will be chosen to ensure they are in the early stages of these conditions and can safely undergo treatment and testing, which includes blood draws and spinal taps.

Inclusion Criteria

I am between 55 and 85 years old with mild cognitive impairment due to Alzheimer's.

Study Partner is available who has frequent contact with the participant and can accompany the participant to most visits

I am between 55 and 85 years old.

Exclusion Criteria

History of schizophrenia (DSM V criteria)

I do not have any serious or unstable health conditions.

History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 250, 500, 750 mg 2-HOBA acetate or placebo TID for 16 weeks. Blood and CSF are collected to measure biomarkers.

16 weeks

Regular visits for monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 2-Hydroxybenzylamine (2-HOBA)

Trial Overview The study tests different doses of a compound called 2-HOBA acetate (250, 500, or 750 mg) taken three times daily against a placebo to see if it's safe and affects certain biomarkers related to Alzheimer's disease over a period of 16 weeks.

How Is the Trial Designed?

Group I: 250 mg 2-HOBA acetate Active Control 1 Intervention

250 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Group II: 500 mg 2-HOBA acetate Active Control 1 Intervention

500 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Group III: 750 mg 2-HOBA acetate Active Control 1 Intervention

750 mg of 2-hydroxybenzylamine (2-HOBA) acetate TID for 16 weeks.

Group IV: Placebo Placebo Group 1 Intervention

Placebo treatment TID for 16 weeks.

Who Is Running the Clinical Trial?

MTI Biotech Inc

Lead Sponsor

Trials

1

Recruited

50+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/9564351

2-Hydroxybenzylamine for the prevention of Alzheimer's ... In this project, we propose to do single and multiple escalation dose studies necessary to characterize pharmacokinetics, metabolism, and safety of 2-HOBA. We ...

2. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/2-Hydroxybenzylamine-Cognitive-Vitality-For-Researchers.pdf

2-Hydroxybenzylamine Reactive carbonyl scavengers, such as 2-HOBA, are likely to be most effective at early stages to slow disease progression, or as a preventative to delay disease ...

3. neurodegenerationresearch.eu neurodegenerationresearch.eu/survey/2-hydroxybenzylamine-for-the-prevention-of-alzheimers-disease-initial-evaluation-in-humans/

2-Hydroxybenzylamine for the prevention of Alzheimers ... We have found that 2-hydroxybenzylamine (2-HOBA) reacts 1,600-fold faster with BFEs than lysine, preventing protein modification in vitro and in vivo.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6321651/

First-in-human study assessing safety, tolerability, and ... 2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate for continued development as a ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0278691518306914

In vitro safety pharmacology evaluation of 2 ... ... Alzheimer's disease (Davies et al., 2011). These results provide promising data supporting a potential benefit of 2-HOBA supplementation in humans; however ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31907026/

a double-blind, randomized, placebo-controlled clinical trial Results: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within ...