Study of Harmine in Healthy Subjects

NCT05526430 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GCO 20-14581R01DK128242-01A1
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The present study is a phase 1 dose escalation study of harmine in healthy volunteers. The primary goal of the trial is to determine the maximum tolerated dose of harmine.

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity (DLT)

  DLT which is defined if have any one of the following: Patient Rated Inventory of Side Effects (PRISE): 0-51, higher scores indicate more adverse events observed Brief Psychiatric Rating Scale (BPRS): 4 - 28, higher scores indicate more symptoms of psychosis Vitals: blood pressure and heart rate will all be measured - anything outside of the following ranges will be noted: * Symptomatic hypotension, or \> 20% decrease in systolic blood pressure (SBP) from pre-dosing and an absolute SBP \< 90; or * Symptomatic hypertension, or \> 20% increase in SBP or diastolic blood pressure (DBP) from predosing and absolute SBP \> 170 or DBP \> 95; * New onset tachycardia (heart rate \>100 bpm) and \>20% increase from pre-dosing; or symptomatic bradycardia (heart rate \<60 bpm) and \> 20% decrease from pre-dosing. * Signs and symptoms of cardiac ischemia, defined by acute ischemic changes on ECG with or without concomitant symptoms

  24 hours

• Maximum Tolerated Dose (MTD) of Oral Harmine HCl Based on Dose Limiting Toxicity (DLT)

  The MTD was determined to be between 100 and 200mg and is weight-based.

  24 hours

Secondary Outcomes (20)

• Visual Analog Scale (VAS) - Nausea

  baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours

• Visual Analog Scale (VAS) - Hunger

  baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours

• Visual Analog Scale (VAS) - Feeling High/Intoxicated

  baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours

• Visual Analog Scale (VAS) - Drowsiness

  baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours

• Visual Analog Scale (VAS) - Anxiety

  baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours

Study Arms (1)

Harmine Dose

EXPERIMENTAL

There will be a total of seven possible doses that include 100 mg, 200 mg, 300 mg, 500 mg, 700 mg, 900 mg and 1200 mg. Each study subject will receive a single oral dose of harmine in this single ascending dose design.

Drug: Harmine Hydrochloride Capsules

Interventions

Harmine Hydrochloride Capsules DRUG

capsules taken orally

Harmine Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18-55 years;
• Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process;
• Body Mass Index (BMI) between 19 and 30;
• Women of childbearing potential and men must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator;
• Women must not be breastfeeding;

You may not qualify if:

• Children under the age of 18 and adults over the age of 55 due to concerns regarding neurodevelopmental and neurocognitive effects, respectively.
• Individuals who are underweight as defined as a BMI \<19, or who are obese as defined as \>30 according to the Centers for Disease Control (CDC). These criteria are in line with the goals of a phase I dose finding and pharmacokinetic study.
• Presence of a significant medical illness i.e., delirium, metastatic cancer, decompensated cardiac, liver or kidney failure, major surgery, stroke or myocardial infarction during the three months prior to entry;
• Presence of a significant neurological disease such as Parkinson's disease, primary or secondary seizure disorders, intracranial tumors, severe head trauma; neurodegenerative diseases;
• Presence of neurocognitive or dementing disorders;
• Presence or history of psychiatric disorder as diagnosed by Mini Neuropsychiatric Interview (MINI);
• Urine toxicology positive for illicit drugs or dis-allowed concomitant medications as per study protocol;
• Medications with primary central nervous system (CNS) effects are dis-allowed, including psychotropic medications, antidepressants, benzodiazepines, centrally acting hypnotic agents, and centrally acting anti-migraine therapies;
• Medications with primary cardiovascular effects are dis-allowed, including beta-adrenergic antagonists, ACE inhibitors, calcium channel blockers, and diuretics;
• Any OTC medications or herbal remedies (see concomitant medications listed above) that could interfere with the study drug, pose a risk to the subject, or contain high tyramine as outlined in the Low Tyramine Diet attachment and above in the concomitant medication summary;
• Any other medications that, in the opinion of the investigators, would pose a safety risk to the patient or that would interfere with the interpretation of study results; Positive pregnancy test at screen or on the morning of the treatment day in women of childbearing potential;
• Systolic blood pressure outside the range of 100 - 140 mmHg, diastolic blood pressure outside the range of 60 - 90 mmHg, and pulse rate at rest \> 100 or \< 60 bpm;
• History of positive tests for hepatitis B surface antigen, hepatitis C antibodies;
• History of HIV;
• Significant ECG abnormalities as follows:

Sponsors & Collaborators

• James Murrough: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Depression and Anxiety Center

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Jessica L Ables
• Organization: Icahn School of Medicine at Mount Sinai

jessica.ables@mssm.edu

(212) 241-2774

Study Officials

• James Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: This study will employ the continual reassessment method (CRM) to find an MTD of Harmine. It uses a statistical model to estimate the relationship between dose and DLT risk to inform decisions on dosing. It first starts with a selected target DLT rate and a mathematical model for the relationship between dose and toxicity, the prior dose-toxicity curve. After a patient experiences a DLT or not, the dose-toxicity curve is re-fit incorporating the latest outcome. The next dose assigned is that most likely to be associated with the target toxicity level (the MTD). At every step, the next patient is assigned the dose estimated to be nearest to the MTD.

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: September 13, 2022
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: January 16, 2025
• Results First Posted: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)