Psilocybin Versus Ketamine in Treatment-Resistant Depression

NCT05383313 | Unknown Phase 2

• 1 other identifier: PSIKET_001CZE
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal is to compare the antidepressant effects of psilocybin and ketamine in patients with TRD versus the antidepressant inactive substance midazolam. The primary endpoint will be the antidepressant effect on the Montgomery- Asberg Depression Rating Scale (MADRS) 24 hours after treatment, the key secondary endpoints being the duration of antidepressant effect, the number of responses and remissions, and the time to standard antidepressant treatment during 3 months of observation. The exploratory part of the study aims to monitor changes in the functional brain states using simultaneous EEG / fMRI, before treatment versus 1 day and 1 week after. Based on literature data and recent data from healthy volunteers who participated in a previous study with psilocybin, the investigator will correlate antidepressant effects of drugs (using psychometric scales and reactions to emotionally salient stimuli (eye tracker)) with entropy and functional connectivity measures. Finally the investigator will explore the role of plasmatic neurobiological biomarkers in depression (BDNF, prolactin, ACTH and oxytocin).

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Verification of the rapid antidepressant effect of Psilocybin compared to Ketamine using the Montgomery-Asberg Depression Rating Scale at 24 hours post administration

  The overall score of the Montgomery-Asberg Depression Rating Scale ranges from 0 to 60, a higher score indicates more severe depression.

  24 hours post drug administration

Secondary Outcomes (5)

• Comparing the response rate and duration of antidepressant effects of Psilocybin or Ketamine versus Midazolam (placebo)

  At days 3, 7, 14, 21, 28, 35, 42, 56 and 84 post drug administration.

• Comparing the remission rate of depression after administration of Psilocybin or Ketamine versus placebo (Midazolam)

  At days 3, 7, 14, 21, 28, 35, 42, 56 and 84 post drug administration.

• Comparing the time to return of depressive symptoms after administration of Psilocybin or Ketamine versus Midazolam (placebo)

  At 12 weeks post drug administration.

• Incidence of Treatment-Emergent Adverse Events

  Through study completion, an average of 1 year.

• Comparing the response rate and duration of antidepressant effects of Psilocybin or Ketamine versus Midazolam (placebo) as rated by participants.

  At days 1, 3, 7, 14, 21, 28, 35, 42, 56 and 84 post drug administration.

Other Outcomes (11)

• Assessment of the antidepressant effect in relation to the acute subjective psychological drug effects

  At the end of dosing day, cca. 6 hours after drug administration

• Assessment of the antidepressant effect in relation to the acute objective psychological drug effects

  At the end of dosing day, cca. 6 hours after drug administration

• Assessment of the antidepressant effect in relation to the retrospective assessment of persistent effects

  At 1, 3, 6 and 12 months post drug administration.

Study Arms (3)

Psilocybin

EXPERIMENTAL

25 mg, orally (capsule), single administration

Drug: Psilocybin

Ketamine

ACTIVE COMPARATOR

250 mg, orally (capsule), single administration

Drug: Ketamine Hydrochloride

Midazolam

PLACEBO COMPARATOR

5 mg, orally (capsule), single administration

Drug: Midazolam Ph. Eur 9.0

Interventions

Psilocybin DRUG

Effect of psilocybin on treatment-resistant depression

Psilocybin

Ketamine Hydrochloride DRUG

Effect of ketamine on treatment-resistant depression

Ketamine

Midazolam Ph. Eur 9.0 DRUG

Effect of midazolam on treatment-resistant depression

Midazolam

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18-65
• Diagnosis of moderate to severe depressive disorder without psychotic symptoms - ICD-10 criteria F32.1-2 or F33.1-2 and at the same time MADRS score \> 20
• The duration of the current depressive episode is at least 3 months and maximum 2 years
• Treatment-resistant depression defined as:
• Failure of at least 2 and at most 4 adequate treatments (6 weeks of full therapeutic dose of antidepressant or adequate non-pharmacological treatment - e.g. psychotherapy, neurostimulation treatment, phototherapy, etc.) within the current depressive episode, using at least 2 types of antidepressants with different pharmacological mechanisms of action (augmentation is taken as a second treatment) or
• Intolerance of 2 different treatments and 1 adequate treatment or
• Intolerance of 3 different antidepressant treatments.
• Ability to understand the study protocol and to be able to complete all study visits and examinations as defined per protocol.
• Participants in a clinical trial of childbearing potential must agree to the use of prescribed contraceptive methods for the duration of the study

You may not qualify if:

• Severe psychiatric comorbidity (axis I MINI, ICD-10 F0.X - F99.X, the intensity of the disorder will be clinically assessed by the study clinician)
• The current depressive phase is severe with psychotic symptoms (ICD-10: F32.3, F33.3)
• MADRS suicidality score (item 10)\> 4
• Duration of the current depressive episode longer than 2 years
• Current drug or alcohol dependence (ICD-10: F17.x) with the exception of tobacco and with the exception of abstinence lasting more than 2 years
• Claustrophobia, inability to undergo MR examination
• Pregnancy or breast-feeding or plan to become pregnant within the next 12 months
• Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP\> 150/100 mmHg)
• Condition after stroke, myocardial infarction in the last 6 months
• Heart failure
• Untreated or decompensated hyperthyroidism
• Glaucoma
• Severe respiratory failure or acute respiratory depression
• History of seizures
• Other serious somatic disease or any other circumstance in which a significant increase in blood pressure would pose a serious threat to health (to be assessed by the study clinician)

Sponsors & Collaborators

• National Institute of Mental Health, Czech Republic: lead
• Czech Health Research Council: collaborator
• Czech Clinical Research Infrastructure Network: collaborator

Study Sites (1)

National Institute of Mental Health

Klecany, 250 67, Czechia

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Psilocybin; Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Vivian Winkler, MD

CONTACT

+420773137373; vivian.winkler@nudz.cz

Nikola Leca, PhD

CONTACT

+420608049831; nikola.leca@nudz.cz

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: May 20, 2022
• Study Start: May 1, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: May 20, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)