Clinical trial NCT05829603: Dose-finding Study for the Combination of DMT and Harmine in Healthy Subjects
Official title: Single-blind, Randomized, Two-arm, Dose-response Study of DMT and Harmine in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Reconnect Labs
Sponsor class: INDUSTRY
First posted: 2023-04-25
Enrollment: 16
Sex: ALL
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: OTHER

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic parameter "Cmax"
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Pharmacokinetic parameter "Area under the curve (AUC)"
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Pharmacokinetic parameter "T1/2"
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: On study days 1,2,3,4,5,6
measure: Blood count (Lab biochemistry)
timeFrame: Changes from baseline to End of Study, an average of 6 weeks
measure: Clinical chemistry (Lab biochemistry)
timeFrame: Changes from baseline to End of Study, an average of 6 weeks
measure: Blood coagulation (Lab biochemistry)
timeFrame: Changes from baseline to End of Study, an average of 6 weeks
measure: QT interval (12-lead Electrocardiogram [ECG])
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Blood pressure
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Heart rate
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Temperature
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
measure: Genotyping
timeFrame: At screening
measure: Subjective effects
timeFrame: Changes from baseline to study days 1,2,3,4,5,6
Secondary outcomes:
measure: Aliveness - Behavioral Task
timeFrame: Changes from baseline to study days 1,2,3
measure: Heart-rate-Variability, Physical Activity, Sleep Patterns
timeFrame: Continuously throughout the study until End of Study, an average of 6 weeks
measure: Heart-rate-variability
timeFrame: Continuously throughout the study until End of Study, an average of 6 weeks
measure: Physical Activity
timeFrame: Continuously throughout the study until End of Study, an average of 6 weeks
measure: Sleep Patterns
timeFrame: Continuously throughout the study until End of Study, an average of 6 weeks
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: University Hospital of Psychiatry Zurich
state: ZH
Study officials:
affiliation: University Hospital of Psychiatry Zurich
name: Erich Seifritz, Prof
role: PRINCIPAL_INVESTIGATOR
References: