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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators propose a phase 1b/2a, randomized, double-blind, placebo-controlled, parallel group dose finding and biomarker study to evaluate the safety, tolerability, and biomarker activity of 2-HOBA in 48 MCI/AD participants. Participants will be randomized 1:1:1:1 to receive 250, 500, 750 mg 2-HOBA acetate TID or placebo for 16 weeks. Blood and cerebral spinal fluid (CSF) will be collected to measure markers of protein modification by dicarbonyls (IsoLGs- \& MDA), pTau-181, YKL-40, and NF-L.

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.

How does the drug 2-HOBA differ from other Alzheimer's treatments?

2-Hydroxybenzylamine (2-HOBA) is unique because it targets oxidative stress, a key factor in Alzheimer's disease, by scavenging reactive carbonyl species, which are harmful compounds that can damage cells. This mechanism is different from many existing Alzheimer's drugs that primarily focus on inhibiting enzymes like acetylcholinesterase or modulating neurotransmitter receptors. ^{1 2 3 4 5}

Research Team

Paul A Newhouse, M.D.

Principal Investigator

Vanderbilt University Medical Center

John A. Rathmacher, Ph.D.

Principal Investigator

MTI Biotech Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

N-Hydroxy-N-Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of novel N,N'-bis-methylenedioxybenzyl-alkylenediamines as bivalent anti-Alzheimer disease ligands. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Alzheimer's disease therapy - an update. [2004]

5. England pubmed.ncbi.nlm.nih.gov

Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease. [2018]