Study of Harmine in Healthy Subjects

Phase 1

Completed

Conditions: Diabetes Mellitus

Interventions: Drug: Harmine Hydrochloride Capsules

Registration Number: NCT05526430

Lead Sponsor: James Murrough

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Harmine Dose	Harmine Hydrochloride Capsules	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicity (DLT)	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
Maximum Tolerated Dose (MTD) of Oral Harmine HCl Based on Dose Limiting Toxicity (DLT)	24 hours	The MTD was determined to be between 100 and 200mg and is weight-based.

Secondary Outcome Measures

Name	Time	Method
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) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
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) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly.
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) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
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) to characterize psychoactive effects of harmine in healthy adults. Full scale from 0-10, with higher scores indicating subjective states are experienced more strongly
Visual Analog Scale (VAS) - Anxiety	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
Visual Analog Scale (VAS) - Depressed Mood	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.
Visual Analog Scale (VAS) - Happy Mood	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
Visual Analog Scale (VAS) - Excitement	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.
Visual Analog Scale (VAS) - Feeling of Control	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.
Visual Analog Scale (VAS) - Vividness of Image	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.
Profile of Mood States Bipolar Scale (POMS-Bi): Composed-Anxious Scale	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
Profile of Mood States Bipolar Scale (POMS-Bi): Agreeable-Hostile Scale	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
Profile of Mood States Bipolar Scale (POMS-Bi): Elated-Depression Scale	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
Profile of Mood States Bipolar Scale (POMS-Bi): Confident-Unsure Scale	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
Profile of Mood States Bipolar Scale (POMS-Bi): Energetic-Tired Scale	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
Profile of Mood States Bipolar Scale (POMS-Bi): Clearheaded-Confused Scale	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
Perceived Stress Scale (PSS)	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
Patient Rated Inventory of Side Effects (PRISE)	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.
Brief Psychiatric Rating Scale (BPRS)	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.
Columbia Suicide Severity Rating Scale (C-SSRS)	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).