Not yet recruitingPhase 1 / Phase 2

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

2-Hydroxybenzylamine (2-HOBA) Phase 1b/2a Proof-of Concept, Dose-Finding, Biomarker Study in Early Alzheimer's Patients

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
55 Years to 85 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 12 weeks
  • Procedures mentioned: Heart tracing (ECG)

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
  • "Tolerability will be assessed by monitoring symptoms, adverse events, vital signs, ECG, and safety labs during the study."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety of different doses of 2-HOBA in 48 adults ages 55–85 with early Alzheimer’s disease or mild memory and thinking problems due to Alzheimer’s. Participants take 2-HOBA or a placebo (a pill with no study drug) for 12 weeks. Blood and fluid from around the brain and spinal cord are tested for signs of disease activity.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 55–85 with mild memory and thinking problems due to Alzheimer’s or mild Alzheimer’s dementia. Meet the study’s memory and daily function test score rules.
  • Have a blood test showing signs of amyloid, a protein that can build up in the brain.
  • Be on stable doses of allowed medicines for at least 4 weeks. Memantine and cholinesterase inhibitors, medicines used for Alzheimer’s, must be stable for at least 12 weeks before screening.
  • Be in good general health, have a depression test score of 14 or less, and see and hear well enough for testing.
  • Have a study partner who has frequent contact with you, such as at least 10 hours a week, and can attend most visits.
  • Speak English fluently, have finished sixth grade or have a good work history, and be able to give written consent.
  • Women must not be pregnant or breastfeeding and must be unable to become pregnant: at least 2 years past menopause or made unable to become pregnant through surgery.
  • Men with partners who could become pregnant must use effective birth control during treatment and for 1 month afterward. They must also avoid donating sperm during that time.

Who can't join

  • Have another serious brain or nerve disease, such as Parkinson’s disease, seizures, or lasting problems from a major head injury.
  • Have had major depression or bipolar disorder in the past year, schizophrenia at any time, or recent behavior problems that could make participation difficult. Alcohol or drug abuse or dependence in the past 2 years also excludes you.
  • Have a serious or unstable health problem that could make the study unsafe or affect results. This includes certain heart, lung, kidney, or liver problems, uncontrolled blood pressure, or uncontrolled diabetes.
  • Have had cancer in the past 5 years, except for certain skin cancers and certain very early cervical or prostate cancers.
  • Have important abnormal results on blood tests or a heart tracing, including vitamin B12 or thyroid tests, or have a blood clotting or bleeding problem.
  • Live in a skilled nursing facility, cannot safely have an MRI scan, or are judged unable to join by the study doctor. MRI barriers include fear of enclosed spaces, certain metal implants, or a pacemaker.
  • Take a medicine the study does not allow, including certain drugs that block a brain chemical called acetylcholine. Recent use of an experimental drug also excludes you; the waiting period is at least 4 weeks and may be longer.
  • Take an MAOI, a type of medicine used for depression and other conditions, or have recently taken one. The waiting period before screening is at least 14 days and may be longer.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: MCI due to AD: 1. Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent. 2. Participant must have a subjective memory concern as reported by participant, study partner, or clinician. 3. Mini-Mental State Exam31 score between 24 and 30, inclusive 4. Clinical Dementia Rating (CDR)32 Global = 0.5. Memory Box score must be at least 0.5 Mild AD: 1. Male or female, aged 55-85 years (both inclusive) at the time of signing informed consent. 2. MCI or Mild dementia of the Alzheimer's type according to the NIA-AA 2018 criteria. 3. CDR global score of 0.5 and CDR domain score of 0.5 or more in at least one of the three instrumental activities of daily living categories (personal care, home \& hobbies, community affairs) Or CDR global score of 1.0 4. MMSE ≥20 Additional Inclusion Criteria for Both Diagnoses: 1. Age 55-85 (inclusive) 2. Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised: * Less than or equal to 11 for 16 or more years of education * Less than or equal to 9 for 8 - 15 years of education * Less than or equal to 6 for 0 - 7 years of education 3. Amyloid positivity established using the C2N Precivity2 Plasma test (Aβ42/40 plus p tau217/np-tau217. (This test uses a statistical algorithm to integrate a patient's Aβ42/40 Ratio and p-Tau217 Ratio to calculate the Amyloid Probability Score 2 (APS2) and determines whether a patient is positive or negative for brain amyloid deposition based on a binary cutoff value). 4. Stable permitted medications for 4 weeks or longer as specified in Section 4.6.3, including: a. Memantine and cholinesterase inhibitors are allowable if stable for 12 weeks prior to screen. 5. Geriatric Depression Scale33 score of less than or equal to 14. 6. Study Partner is available who has frequent contact with the participant (e.g., an average of 10 hours per week or more) and can accompany the participant to most visits to answer questions about the participant. 7. Adequate visual and auditory acuity to allow neuropsychological testing. 8. Good general health with no additional diseases/disorders expected to interfere with the study. 9. For women: participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile). 10. For men: male participants with female partners of childbearing potential must use an effective method of contraception from dosing on Day 1 until 1 month after the lastadministration of study medication and agreed not to donate sperm until 1 month after the last administration of study medication. 11. Completed six grades of education or has a good work history. 12. Must speak English fluently. 13. Provide written informed consent. Participants must have the capacity to consent. Exclusion Criteria: Any other significant neurologic disease including Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities. 2. Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation, or behavioral problems within 3 months, which could lead to difficulty complying with the protocol. 3. History of schizophrenia (DSM V criteria). 4. History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria). 5. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal (defined by eGFR score \<60 mL/min/1.73 m²), hepatic impairment, endocrine, or other systemic disease that, in the opinion of the Investigator, may put the participant at risk because of participation in the study, influence the results, or affect the participant's ability to participate in the study. Participants with moderate or severe hepatic impairment, defined as Child-Pugh Class B or C, are excluded. 6. Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment. 7. Clinically significant abnormalities in B12 or TFTs that might interfere with the study. 8\. Clinically significant abnormalities in screening laboratories or ECG. 9. Residence in a skilled nursing facility. 10. Use of any excluded medication as described in Section 4.6.2, including: * 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.

Study sites (1)

TN

  • Center for Cognitive Medicine, Vanderbilt University Medical Center · Nashville, TN 37212Meagan Adams, MSPM, PMP · Study contact · (615) 421-4352 · meagan.adams@vumc.orgPatricia Andrews, M.D. · Principal investigatorPaul A. Newhouse, M.D. · Sub-investigatorKimberly Albert, Ph.D. · Sub-investigatorMore trials in Nashville