Treatment Resistant DepressionPhase 2PSIKET_001NCT05383313
Psilocybin Versus Ketamine in Treatment-Resistant Depression
A Phase 2 study testing Psilocybin, Ketamine Hydrochloride and Midazolam Ph. Eur 9.0 in people with Treatment Resistant Depression, run by National Institute of Mental Health, Czech Republic at 1 site in Czechia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Psilocybin, Ketamine Hydrochloride and Midazolam Ph. Eur 9.0
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCzechia
- Study dates
- 1 May 2021to 30 Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
- Pacemaker
- Metal implants made of MR incompatible materials
- Regular use of medication that could interact with psilocybin (to be assessed by the investigator)
- Regular use of antipsychotics with 5-HT2A receptor antagonist activity or discontinuation of their use for less than 14 days (eg risperidone, olanzapine, clozapine, quetiapine, ziprasidone)
- Current use of monoamine oxidase inhibitors (MAOIs)
- Previous experience with psilocybin, hallucinogenic mushrooms or ketamine is possible in a maximum of 10% of patients. This experience must not be during the last 12 months or during the current depressive episode.
- Recent use of antidepressants with a direct antagonistic effect on 5-HT2A receptors such as SARI and tetracyclic antidepressants (eg trazodone, mirtazapine, mianserin) or discontinuation of their use for less than 14 days
- Electroconvulsive therapy in the previous 3 months
- Daily use of benzodiazepine anxiolytics higher than the equivalent of 10 mg diazepam
- Allergy to any of the components of study drugs
Trial locations and contacts
1 site in 1 country.
Czechia1 site, 1 recruiting
- Recruiting
National Institute of Mental Health
Klecany, 250 67
Vivian Winkler, MD, 773137373, vivian.winkler@nudz.cz
Nikola Leca, PhD, 608049831, nikola.leca@nudz.cz
About this study
Official title: Psilocybin Versus Ketamine - Fast Acting Antidepressant Strategies in Treatment-resistant Depression
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).
Read the detailed description
The main aim of the study is to verify the efficacy and safety of a single dose of psilocybin 20 mg in the treatment of TRD in adults in a randomized clinical trial with active comparator ketamine 200 mg (rapid onset acting antidepressant) and negative control midazolam 5 mg (drug with no antidepressant properties). Primary objective: 1) verification of the rapid antidepressant effect of psilocybin compared to ketamine using the MADRS scale at 24 hours. Secondary objectives: 1) on days 3, 7 and 14 and 3, 4, 5, 6, 8 and 12 weeks after application of the substances, evaluate / compare: a) the duration of effects of both substances using the MADRS scale b) antidepressant effects according to the subjective evaluation of patients - QIDS scale. c) response rate (50% reduction on the MADRS scale) and remission (MADRS ? 10). 2) time to return of depressive symptoms defined according to the criteria for the use of antidepressants within 12 weeks 3) safety profile of study medication Exploratory objectives: 1) Evaluate the antidepressant effect depending on: a) the intensity of acute psychological effects assessed using the subjective scale of 5D-ASCs and the objective scale of BPRS, b) depending on the retrospective assessment of persistent effects using the Persisting effects scale, c) the degree of eye contact with negative and neutral emotion faces measured by eye-tracking before and after treatment (on days 1 and 7). 2) To evaluate the neurobiology of the antidepressant effect in relation to: a) plasma levels of the major metabolite of psilocin, markers of neuroplasticity, antidepressant effect and stress (BDNF, prolactin, oxytocin, ACTH) at 90 min, 3, and 6 h after administration of study medication compared to pre-administration levels, b) changes in resting-state brain activity (connectivity, entropy) measured by simultaneous EEG / fMRI functional imaging methods before and after 1 and 7 days after treatment.
- Conditions
- Treatment Resistant Depression
- Being tested
- Psilocybin, Ketamine Hydrochloride, Midazolam Ph. Eur 9.0
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
Effect of psilocybin on treatment-resistant depression
Ketamine HydrochlorideDrug
Effect of ketamine on treatment-resistant depression
Midazolam Ph. Eur 9.0Drug
Effect of midazolam on treatment-resistant depression
| Study group | Role | What they receive |
|---|---|---|
| Psilocybin | Experimental | 25 mg, orally (capsule), single administration Receives: Drug: Psilocybin |
| Ketamine | Active comparator | 250 mg, orally (capsule), single administration Receives: Drug: Ketamine Hydrochloride |
| Midazolam | Placebo comparator | 5 mg, orally (capsule), single administration Receives: Drug: Midazolam Ph. Eur 9.0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours post drug administration
Secondary outcomes (5)
Comparing the response rate and duration of antidepressant effects of Psilocybin or Ketamine versus Midazolam (placebo)
Response rate defined as a 50% reduction on the Motgomery-Asberg Depression Rating Scale (range 0 to 60, a higher score indicates more severe depression).
Measured: 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)
Remission (defined as a score of ≤10 on the Montgomery-Asberg Depression Rating Scale).
Measured: 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)
Return of depressive symptoms as defined by the clinical need to prescribe antidepressant medication by the study clinician. Criteria for the prescription of antidepressant medication are defined in the study protocol.
Measured: At 12 weeks post drug administration.
Incidence of Treatment-Emergent Adverse Events
The safety of the study medications will be assessed by the analysis of the incidence of treatment-emergent adverse events
Measured: 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.
Assessment via the Quick Inventory of Depressive Symptomatology (QIDS) which rates depression symptoms via self-assessment. Total QIDS scores range from 0 to 27 with higher scores indicating more severe depression.
Measured: At days 1, 3, 7, 14, 21, 28, 35, 42, 56 and 84 post drug administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2022
- Study start1 May 2021
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health, Czech Republic
- Sponsor type
- University, hospital or other
- Collaborators
- Czech Health Research Agency, Czech Clinical Research Infrastructure Network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05383313
- Sponsor's protocol ID
- PSIKET_001CZE
- Acronym
- PSIKET_001
- Status last verified
- Sep 2021
- First submitted
- 7 Sep 2021
- Last updated
- 20 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin Versus Ketamine - Fast Acting Antidepressant Strategies in Treatment-resistant Depression
- ClinicalTrials.gov ID
- NCT05383313
- Acronym / sponsor ID
- PSIKET_001 / PSIKET_001CZE
- Conditions
- Treatment Resistant Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Institute of Mental Health, Czech RepublicUniversity, hospital or other
- Collaborators
- Czech Health Research Agency, Czech Clinical Research Infrastructure Network
- Study start
- 1 May 2021 (actual)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 20 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The main aim of the study is to verify the efficacy and safety of a single dose of psilocybin 20 mg in the treatment of TRD in adults in a randomized clinical trial with active comparator ketamine 200 mg (rapid onset acting antidepressant) and negative control midazolam 5 mg (drug with no antidepressant properties). Primary objective: 1) verification of the rapid antidepressant effect of psilocybin compared to ketamine using the MADRS scale at 24 hours. Secondary objectives: 1) on days 3, 7 and 14 and 3, 4, 5, 6, 8 and 12 weeks after application of the substances, evaluate / compare: a) the duration of effects of both substances using the MADRS scale b) antidepressant effects according to the subjective evaluation of patients - QIDS scale. c) response rate (50% reduction on the MADRS scale) and remission (MADRS ? 10). 2) time to return of depressive symptoms defined according to the criteria for the use of antidepressants within 12 weeks 3) safety profile of study medication Exploratory objectives: 1) Evaluate the antidepressant effect depending on: a) the intensity of acute psychological effects assessed using the subjective scale of 5D-ASCs and the objective scale of BPRS, b) depending on the retrospective assessment of persistent effects using the Persisting effects scale, c) the degree of eye contact with negative and neutral emotion faces measured by eye-tracking before and after treatment (on days 1 and 7). 2) To evaluate the neurobiology of the antidepressant effect in relation to: a) plasma levels of the major metabolite of psilocin, markers of neuroplasticity, antidepressant effect and stress (BDNF, prolactin, oxytocin, ACTH) at 90 min, 3, and 6 h after administration of study medication compared to pre-administration levels, b) changes in resting-state brain activity (connectivity, entropy) measured by simultaneous EEG / fMRI functional imaging methods before and after 1 and 7 days after treatment.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Psilocybin | Experimental | Drug: Psilocybin25 mg, orally (capsule), single administration |
| Ketamine | Active comparator | Drug: Ketamine Hydrochloride250 mg, orally (capsule), single administration |
| Midazolam | Placebo comparator | Drug: Midazolam Ph. Eur 9.05 mg, orally (capsule), single administration |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Ability to understand the study protocol and to be able to complete all study visits and examinations as defined per protocol.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PsilocybinEffect of psilocybin on treatment-resistant depression | Drug | Psilocybin |
| Ketamine HydrochlorideEffect of ketamine on treatment-resistant depression | Drug | Ketamine |
| Midazolam Ph. Eur 9.0Effect of midazolam on treatment-resistant depression | Drug | Midazolam |
Primary outcome
Verification of the rapid antidepressant effect of Psilocybin compared to Ketamine using the Montgomery-Asberg Depression Rating Scale at 24 hours post administration
Time frame: 24 hours post drug administration
The overall score of the Montgomery-Asberg Depression Rating Scale ranges from 0 to 60, a higher score indicates more severe depression.
5 secondary outcomes
Comparing the response rate and duration of antidepressant effects of Psilocybin or Ketamine versus Midazolam (placebo)
Time frame: 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)
Time frame: 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)
Time frame: At 12 weeks post drug administration.
Incidence of Treatment-Emergent Adverse Events
Time frame: 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.
Time frame: At days 1, 3, 7, 14, 21, 28, 35, 42, 56 and 84 post drug administration.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin, Ketamine Hydrochloride and Midazolam Ph. Eur 9.0 in people with Treatment Resistant Depression, run by National Institute of Mental Health, Czech Republic at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vivian Winkler, MD (+420773137373, vivian.winkler@nudz.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verification of the rapid antidepressant effect of Psilocybin compared to Ketamine using the Montgomery-Asberg Depression Rating Scale at 24 hours post administration (time frame: 24 hours post drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2022.