2-Hydroxybenzylamine (2-HOBA) Study in Early Alzheimer's Patients

ConditionsAlzheimer Disease Mild Cognitive Impairment

Trial statusNot yet recruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age55-85

SponsorMTI Biotech Inc

About 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 mg BID, 250 and 500 mg 2-HOBA acetate TID or placebo for 12 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent.

Participant must have a subjective memory concern as reported by participant, study partner, or clinician.

Mini-Mental State Exam31 score between 24 and 30, inclusive

Clinical Dementia Rating (CDR)32 Global = 0.5. Memory Box score must be at least 0.5

Disqualifiers

Use centrally acting anti-cholinergic drugs.

Use of any investigational drugs within 4 weeks or 5 half-lives, whichever is longer, prior to screening. 11. A current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening. 12. Contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker. 13. Participants whom the Site PI deems to be otherwise ineligible. 14. Current use of monoamine oxidase inhibitors (MAOIs) or use within 14 days (or 5 half-lives, whichever is longer) prior to screening, This includes non-selective MAOIs (phenelzine, tranylcypromine, isocarboxazid), MAO-B inhibitors (selegiline, rasagiline, safinamide), reversible MAO-A inhibitors (moclobemide), and other agents with MAOI A inhibitory activity (linezolid, methylene blue at doses >1 mg/kg). This exclusion is required because 2-HOBA has demonstrated MAO-A inhibitory activity in vitro.

Trial design

Design model

Parallel

Treatments tested in this trial

2-hydroxybenzylamine acetate
Drug
2-hydroxybenzylamine acetate (2-HOBA) is taken daily for 12 weeks
Placebo
Other intervention
Placebo taken three times per day for 12 weeks.

Treatment groups

48 Participants

are divided into 4 treatment groups

Group A: PlaceboPlacebo comparator 1 intervention

Group B: 250 mg 2-HOBA acetate BIDActive comparator 1 intervention

Group C: 250 mg 2-HOBA acetate TIDActive comparator 1 intervention

Group D: 500 mg 2-HOBA acetateActive comparator 1 intervention

Trial outcomes

Primary outcomes

Safety/Tolerability (adverse events)

Rates of adverse events will be compared between active and placebo arms and presented as summary statistics.

Time frame

Baseline to week 12

Change in dicarbonyl protein adducts

Change in CSF levels of the dilysyl-malondialdehyde crosslink and the lysyl-levuglandin adduct of CSF proteins in a dose-responsive relationship

Time frame

Baseline to week 12

Secondary outcomes

Compliance

Treatment compliance will be assessed through pill counts at Week 8 and 16

Time frame

Baseline to week 12

Measurement of biomarker, p-Tau181

Change in phosphorylated-Tau-181 levels in CSF and plasma:

Time frame

Baseline to week 12

Measurement biomarker, human cartilage glycoprotein 39 (YKL-4)

Change in plasma concentration of human cartilage glycoprotein 39 (YKL-4)

Time frame

Baseline to week 12

Measurment of biomarker, neurofilaments light chain protein (NF-L)

Change in the concentration of neurofilaments light chain protein (NF-L) in CSF and plasma

Time frame

Baseline to week 12

Other outcomes

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Change in the total score for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Time frame

Baseline to Week 12

Activities of Daily Living (ADL)

For Activities of Daily Living (ADLs), the Alzheimer's disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale to assess the competence of participants in basic and instrumental ADLs will be utilized. A lower score indicates greater functional impairment.

Time frame

Baseline to Week 12

Quantitative Electroencephalography (EEG)

The change participants' electrical brain activity will be monitored using noninvasive scalp electrodes. Event-related potentials (ERP), or time-locked EEG, will be used to evaluate cognitive processes.

Time frame

Baseline to Week 12

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

MTI Biotech Inc

Lead sponsor

Vanderbilt University Medical Center

Collaborator

Source ClinicalTrials.gov

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