DHTP: Dose-finding Study for the Combination of DMT and Harmine in Healthy Subjects

• Sponsor: Reconnect Labs (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05829603
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 3
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to compare corresponding inter- and intraindividual pharmacokinetic and pharmacodynamic profiles including assessments of safety & tolerability.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Dimethyltryptamin (DMT) & Harmine	Phase 1

Detailed Description

Participants will undergo a series of six study days with varying doses of DMT and Harmine. The intervention is embedded in controlled environment and continuous psychological support. Pharmacokinetic and pharmacodynamic assessments are obtained over the course of 24 hours on each study visit to estimate dose-exposure relationship and drug-drug-interaction. Additionally, the occurrence of adverse events will be closely monitored throughout the whole study.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Each participants will be randomized into one of two sequences. Each sequence consists of six study days with a minimum of 1 day between each study day. The differences between the sequences are a) the order of dosages administered to minimize confounding effects through expectancy and b) a study day containing only one of the two active ingredients, thus covering each combination in a factorial, cross-over design.Each participants will be randomized into one of two sequences. Each sequence consists of six study days with a minimum of 1 day between each study day. The differences between the sequences are a) the order of dosages administered to minimize confounding effects through expectancy and b) a study day containing only one of the two active ingredients, thus covering each combination in a factorial, cross-over design.
• Masking: Single (Participant)
• Masking Description: Participants are blinded regarding their allocated study condition as well as the order of doses administered. However, participants are informed about the range and the number of different dosages administered.
• Primary Purpose: Other
• Official Title: Single-blind, Randomized, Two-arm, Dose-response Study of DMT and Harmine in Healthy Subjects
• Anticipated Study Start Date: May 1, 2023
• Anticipated Primary Completion Date: Jul 1, 2023
• Anticipated Study Completion Date: Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence A Six varying doses of a fixed-combination of Dimethyltryptamin (DMT) and harmine	Drug: Dimethyltryptamin (DMT) & Harmine; Six varying doses of a fixed-combination formulation of Dimethyltryptamin (DMT) and harmine; Other Names: RE01
Experimental: Sequence B Six varying doses of a fixed-combination of Dimethyltryptamin (DMT) and harmine	Drug: Dimethyltryptamin (DMT) & Harmine; Six varying doses of a fixed-combination formulation of Dimethyltryptamin (DMT) and harmine; Other Names: RE01

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic parameter "Cmax" [Changes from baseline to study days 1,2,3,4,5,6]

   Dose-dependent changes in Cmax of several doses of combined DMT & Harmine

2. Pharmacokinetic parameter "Area under the curve (AUC)" [Changes from baseline to study days 1,2,3,4,5,6]

   Dose-dependent changes in AUC of several doses of combined DMT & Harmine

3. Pharmacokinetic parameter "T1/2" [Changes from baseline to study days 1,2,3,4,5,6]

   Dose-dependent changes in T1/2 of several doses of combined DMT & Harmine

4. Incidence of Treatment-Emergent Adverse Events [On study days 1,2,3,4,5,6]

   Dose-dependent changes in incidence of adverse drug reactions

5. Blood count (Lab biochemistry) [Changes from baseline to End of Study, an average of 6 weeks]

   Changes from baseline in blood count

6. Clinical chemistry (Lab biochemistry) [Changes from baseline to End of Study, an average of 6 weeks]

   Changes from baseline in any clinical chemistry parameter with potential clinical relevance.

7. Blood coagulation (Lab biochemistry) [Changes from baseline to End of Study, an average of 6 weeks]

   Changes from baseline in blood coagulation

8. QT interval (12-lead Electrocardiogram [ECG]) [Changes from baseline to study days 1,2,3,4,5,6]

   Dose-dependent changes of QT intervals assessed by clinical 12-lead ECG)

9. Blood pressure [Changes from baseline to study days 1,2,3,4,5,6]

   Dose-dependent changes in systolic and diastolic blood pressure

10. Heart rate [Changes from baseline to study days 1,2,3,4,5,6]

    Dose-dependent changes in heart-rate

11. Temperature [Changes from baseline to study days 1,2,3,4,5,6]

    Dose-dependent changes in body temperature (in °C)

12. Genotyping [At screening]

    Collection of saliva-samples to determine genetic polymorphisms

13. Subjective effects [Changes from baseline to study days 1,2,3,4,5,6]

    Dose-dependent changes in trajectories of subjective effects

Secondary Outcome Measures

1. Aliveness - Behavioral Task [Changes from baseline to study days 1,2,3]

   Validated instrument developed to assess dose-dependent changes in perceived aliveness.

2. Heart-rate-Variability, Physical Activity, Sleep Patterns [Continuously throughout the study until End of Study, an average of 6 weeks]

   Wearable device for continuous sensor assessments

3. Heart-rate-variability [Continuously throughout the study until End of Study, an average of 6 weeks]

   Occurence of dose-dependent changes in heart-rate-variability assessed by a wearable device

4. Physical Activity [Continuously throughout the study until End of Study, an average of 6 weeks]

   Occurence of dose-dependent changes in physical activity assessed by a wearable device

5. Sleep Patterns [Continuously throughout the study until End of Study, an average of 6 weeks]

   Occurence of dose-dependent changes in sleep patterns assessed by a wearable device

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained

• Willing to refrain from drinking alcohol one day before testing days and caffeinated drinks at the testing days and from consuming psychoactive substances or other medications for 2 weeks before testing days and for the duration of the study

• Already experienced with psychedelic substances (at least 5 prior experiences - microdoses do not count)

• Able and willing to comply with all study requirements

• Informed consent form was signed

• Good knowledge of the German language

• Participant informs study physicians / project scientists about simultaneous treatment or therapy with other physicians and about current intake of psychotropic substances or medication

• Women of childbearing potential are required to use effective, established contraception, such as oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

Exclusion Criteria:

• Previous significant adverse response to a hallucinogenic drug

• Participation in another study where pharmaceutical compounds will be given

• Presence of Axis I affective, anxiety, or dissociative disorders

• Present or antecedent diagnosis of bipolar disorder (I, II, not otherwise specified), schizophrenia, schizoaffective disorder, psychosis, or other disorders from the psychotic spectrum

• First-degree relatives with present or antecedent schizophrenia, schizoaffective disorder, or bipolar disorder type I

• History of head trauma, seizures, cancer, or cerebrovascular accidents

• Recent cardiac or brain surgery

• Current addiction of medication or psychotropic substances (including nicotine addiction) according to SCID I criteria

• Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine)

• Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardical infarction, coronary spastic angina)

• Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease)

• Cerebrovascular disease (e.g. stroke, intracranial bleeding / hemorrhage, intracranial aneurysm)

• Serious abnormalities in ECG or blood count/chemistry

• Liver or renal or pulmonary disease

• Pregnant or breastfeeding women (a urine pregnancy test will be done for all women capable of bearing children), occurrence of premenstrual dysphoric disorder (PMDD)

• Current use of medications with significant interaction potential with MAOI (e.g. antidepressants, antipsychotics, psychostimulants, dopaminergic/serotonergic agents, anticonvulsants)

• high risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g. evidence of serious personality disorder, serious current stressors, lack of social support)

Optional wearable data collection (pilot and main study):

Additional inclusion criterion for health data collection sub-cohort using TeleWear and accompanying wearable: possession of a smartphone capable of running the latest version of the TeleWear application and Withings® HealthMate application.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Psychiatry Zurich	Zürich	ZH	Switzerland	8032

Sponsors and Collaborators

• Reconnect Labs

Investigators

• Principal Investigator: Erich Seifritz, Prof, University Hospital of Psychiatry Zurich

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reconnect Labs
• ClinicalTrials.gov Identifier: NCT05829603
• Other Study ID Numbers: DMT-HAR-TOM-P
• First Posted: Apr 25, 2023
• Last Update Posted: Apr 25, 2023
• Last Verified: Apr 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Harmine

Study Results

No Results Posted as of Apr 25, 2023