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Completed

NCT Number: NCT05526430

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.

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Key information

Conditions

Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Depression and Anxiety Center

New York, 10029, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Harmine Hydrochloride Capsules

Drug

capsules taken orally

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicity (DLT)

    Time frame: 24 hours

    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

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

    Time frame: 24 hours

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

Secondary outcomes

  1. Visual Analog Scale (VAS) - Nausea

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

    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

  2. Visual Analog Scale (VAS) - Hunger

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

    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.

  3. Visual Analog Scale (VAS) - Feeling High/Intoxicated

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

    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

  4. Visual Analog Scale (VAS) - Drowsiness

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

    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

  5. Visual Analog Scale (VAS) - Anxiety

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

    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

  6. Visual Analog Scale (VAS) - Depressed Mood

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

    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.

  7. Visual Analog Scale (VAS) - Happy Mood

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

    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

  8. Visual Analog Scale (VAS) - Excitement

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

    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.

  9. Visual Analog Scale (VAS) - Feeling of Control

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

    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.

  10. Visual Analog Scale (VAS) - Vividness of Image

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

    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.

  11. Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  12. Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  13. Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  14. Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  15. Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  16. Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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

  17. Perceived Stress Scale (PSS)

    Time frame: 24 hours

    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

  18. Patient Rated Inventory of Side Effects (PRISE)

    Time frame: 24 hours

    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.

  19. Brief Psychiatric Rating Scale (BPRS)

    Time frame: Baseline, 2, 6, 7, 8, and 24 hours

    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.

  20. Columbia Suicide Severity Rating Scale (C-SSRS)

    Time frame: 24 hours

    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).

Sponsors and collaborators

Lead sponsor

James Murrough

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

A Phase I Dose Escalation Study of Harmine in Healthy Subjects

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Sep 2, 2022
Registry last updated
Jan 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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