Study of Harmine in Healthy Subjects

A Phase I Dose Escalation Study of Harmine in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Harmine Hydrochloride Capsules

Detailed Description

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. Harmine will be administered in an open-label, dose escalation design that will use the continual reassessment method to inform the next dose to test in a subject. 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. On the treatment day, subjects will undergo continuous medical monitoring. All adverse events will be documented and events that qualify as dose limiting toxicities (DLTs) will be used to inform dosing for the subsequent subjects.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Depression and Anxiety Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• 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;

Exclusion Criteria

• 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:
• Heart Rate < 60 and >100 bpm
• PR Interval <120 and > 220 ms
• QRS duration < 70 and >120 ms
• QTC Interval (Bazett) > 450 ms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Harmine Dose; 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; capsules taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS) - Nausea	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Hunger	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Feeling High/Intoxicated	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Drowsiness	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Anxiety	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Depressed Mood	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Happy Mood	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Excitement	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Feeling of Control	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Visual Analog Scale (VAS) - Vividness of Image	Visual Analog Scale (VAS) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.	baseline, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale	The POMS-Bi is a 72-item psychological self-report rating scale used to assess transient, distinct mood states. It is also a validated instrument for identifying the effects of drug treatments. Items are rated on a four-point scale from 0 "much unlike this" to 3 "much like this." It includes six bipolar scales: composed-anxious, agreeable-hostile, elated-depressed, confident-unsure, energetic-tired, and clearheaded-confused. Each subscale is scored 0-36, with higher scores associated with better mood	Baseline, 2, 6, 7, 8, and 24 hours
Perceived Stress Scale (PSS)	The PSS is a 10-item self-report scale that measures the perception of stress. Each item is rated on a scale from 0-4. Full scale from 0-40, with higher score indicating more perceived stress	24 hours
Patient Rated Inventory of Side Effects (PRISE)	The PRISE is a self-report Adverse Event (AE) Checklist used to qualify side effects by identifying and evaluating the tolerability of each symptom. Only new onset or worsening symptoms were included. Participants could report more than one AE.	24 hours
Brief Psychiatric Rating Scale (BPRS)	The BPRS is a 16-item clinician- administered scale that captures acute behavioral changes throughout treatment. Each item is rated on a scale from 1-7. Full scale from 16-112 with higher score indicating more worse health outcomes.	Baseline, 2, 6, 7, 8, and 24 hours
Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS is a clinician-administered suicidal ideation and behavior rating scale used to evaluate suicide risk. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).	24 hours

Collaborators and Investigators

• Sponsor: James Murrough
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: James Murrough, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: August 31, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Monoamine Oxidase Inhibitors; Hallucinogens; Harmine
• Other Study ID Numbers: GCO 20-1458; 1R01DK128242-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As of now the study team is not plan on sharing IPD as that would not align with the approved management plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No