This study has been transitioned to CTIS with ID 2024-518020-68-00 check the CTIS register for the current data. Primary:Part A: To assess the safety and tolerability of single ascending doses of DMT in healthy subjects, when given by IV infusion.…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability: Vital signs (heart rate, blood pressure, respiratory
rate and temperature), 12-lead electrocardiograms (ECGs), physical examination,
laboratory safety tests (haematology, clinical chemistry, coagulation, and
urinalysis), local tolerability at infusion site, Columbia-Suicide Severity
Rating Scale (C SSRS), occurrence of psychotic symptoms (BPRS), occurrence of
central 5-HT toxicity (Hunters criteria + CPK)and adverse events (AEs).
Secondary outcome
PK: Cmax, tmax, AUClast, AUC0-t, AUCinf, %AUCextrap, t*, CL, Vss, Vz, MRTinf,
and *z of DMT.
Background summary
Each year, 16.9 million people worldwide suffer a first stroke, and there are
5.9 million stroke related deaths (based on 2010 data). Accordingly, stroke is
the second or third most common cause of death and one of the main causes of
acquired adult disability. About 80% of stroke survivors have motor impairments
of the upper limb that gravely affect their ability to perform activities of
daily living (ADL) and to participate socially.
The severity of upper limb paresis has been identified as an independent
determinant of the outcome of basic ADL after a stroke. Constraint-induced
movement therapy (CIMT), or modified versions of CIMT (mCIMT), are currently
considered the most effective treatment regimens in physical therapy to improve
the outcome of the upper paretic limb.
Neurophysiologic mechanisms believed to underline the treatment benefits of
CIMT include overcoming learned non-use, and neuroplasticity. Structural brain
changes and increases in grey matter and motor areas have been observed in
patients undergoing CIMT after stroke.
N,N-dimethyltryptamine (DMT) is a naturally occurring methylated
indolealkylamine possessing potent psychotropic en neuroplastic properties. It
is being developed as a supplement to constraint-induced movement therapy
(CIMT) for the treatment of upper-limb dysfunction in patients who have
experienced stroke.
Study objective
This study has been transitioned to CTIS with ID 2024-518020-68-00 check the CTIS register for the current data.
Primary:
Part A: To assess the safety and tolerability of single ascending doses of DMT
in healthy subjects, when given by IV infusion.
Part B: To assess the safety and tolerability of fixed repeated doses of DMT in
healthy subjects, when given three times weekly over two weeks by IV infusion.
Secondary
Part A: To assess the pharmacokinetics (PK) of single ascending doses of DMT in
healthy subjects, when given by IV infusion.
Part B: To assess the PK of fixed repeated doses of DMT in healthy subjects,
when given at three times weekly over two weeks by IV infusion.
Exploratory
Part A: To assess the pharmacodynamics (PD) of ascending single doses of DMT in
healthy subjects, when given by IV infusion.
Part B: To assess the PD of fixed repeated doses of DMT in healthy subjects,
when given three times weekly over two weeks by IV infusion.
Study design
This is a phase 1, double-blind, randomised, placebo-controlled trial done in
two parts.
Part A will assess the safety, tolerability, PK and PD of ascending single IV
doses of DMT.
Part B will assess the safety, tolerability, PK and PD of fixed 6 times
repeated IV doses of DMT.
Intervention
Part A
Single dose DMT or placebo infusion (bolus followed by 6-h infusion)
Part B
Three dosages DMT or placebo per week for two weeks (bolus followed by 6-h
infusion)
Study burden and risks
The principal mitigations for potential risks of the study drug are:
- The selection of dose levels that were previously shown to be safe and
tolerable in subjects.
- Thorough preparation of the study subjects regarding the trial.
- Selection of subjects that have no prior history of psychiatric illness or
family history of psychiatric illness, as this will reduce the chances of
subjects developing psychiatric complaints due to the study drug significantly.
- Prespecified safety monitoring procedures.
- The trial facility, where close monitoring can be performed and rapid
institution of appropriate care can be given.
Potential risks can be monitored clinically and/or with laboratory tests and
have been considered when determining the stopping rules for this clinical
trial.In addition to the potential risks associated with study drug
administration, there is minimal risk associated with trial procedures
includinginsertion of a canula for withdrawing blood (limited to < 500 mL) and
non-invasive procedures including vital sign assessments,electrocardiograms
(ECGs) and PD assessments. Overall, the benefit-risk profile is considered
appropriate for this trial
West Broadway 400-601
Vancouver, V5Z 4C2
CA
West Broadway 400-601
Vancouver, V5Z 4C2
CA
Listed location countries
Age
Inclusion criteria
Normotensive male or female volunteers, deemed healthy on the basis of a
clinical history, physical examination, ECG, vital signs, and laboratory tests
of blood and urine; agree to follow the contraception requirements of the
trial; able to give fully informed written consent.
Exclusion criteria
Positive tests for hepatitis B & C, HIV; severe adverse reaction to any drug;
history of adverse (psychological) reaction to DMT or other serotonergic
psychedelic drugs; drug or alcohol abuse; use of over-the-counter medication
(with the exception of common analgesics, eg paracetamol [acetaminophen] or
ibuprofen) or receipt of coronavirus disease 2019 (COVID 19) vaccination during
the 7 days before the first dose of trial medication, or use of prescribed
medication during the 14 days before first dose of trial medication, or
monoamine oxidase inhibitors (MAOI) during the 30 days before the first dose of
trial medication; participation in other clinical trials of unlicensed
medicines, or loss of more than 400 mL blood, within the previous 90 days;
vital signs outside the acceptable range; positive urine drug test; clinically
relevant abnormal findings at the screening assessment; acute or chronic
illness; significant suicide risk identified from the C SSRS, previous suicidal
behaviour/ideation, or clinical assessment; clinically relevant abnormal
medical history or concurrent medical condition (including psychotic or seizure
disorders); close (first and second degree) relative with schizophrenia
spectrum or other psychotic, bipolar or related disorder; persistent
psychological effects following the previous use of psychedelics; possibility
that volunteer will not cooperate; pre-menopausal women who are pregnant or
lactating, or are sexually active and not using a reliable method of
contraception.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518020-68-00 |
| EudraCT | EUCTR2022-002411-30-NL |
| CCMO | NL81883.056.22 |