Antidepressant effects of psilocybin in pharmaco-resistant depression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodni Ustav Dusevniho Zdravi

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

21 Nov 2024 → ongoing

Decision date (initial)

2024-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Academic clinical trial is financially supported by grants and the sponsor organization

External identifiers

EU CT number

2024-515899-13-00

EudraCT number

2018-004480-31

ClinicalTrials.gov

NCT05383313

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Others, Efficacy, Pharmacokinetic, Dose response

The primary aim of the study is to verify the rapid antidepressant effect of psilocybin 25 mg in comparison
with ketamine 250 mg using the MADRS scale completed 24 hours after a single application of the study medication. We assume that after 24 hours psilocybin 25 mg and ketamine 250 mg will have similar antidepressant effects effect (decrease in depressive symptoms according to the MADRS scale) and at the same time the effect will be more pronounced with both substances
compared to the antidepressant ineffective midazolam 5 mg.

Secondary objectives 6

1. A key secondary objective will be the evaluation of the duration of the rapid antidepressant effect in the first two weeks (days 3, 7 and 14) after psilocybin 25 mg compared to ketamine 250 mg (the effect of which usually does not exceed one week after a single administration) using the MADRS scale. We assume that after just one week, the antidepressant effect of psilocybin will be more significant in compared to ketamine and this difference will be even more pronounced after 2 weeks of a single application.
2. Comparison of the duration of the antidepressant effect of psilocybin compared with ketamine and midazolam after the end of hospitalization, i.e. 3, 4, 5, 6, 8 and 12 weeks after application using the MADRS scale
3. Comparison of the antidepressant effect of a single application of psilocybin, ketamine and midazolam after 24 h, 1, 2, 3, 4, 5, 6, 8 and 12 weeks after application according to subjective evaluation by the patients themselves - the QIDS scale.
4. Comparison of response rates (50% reduction in MADRS score) and remission rates (MADRS ≤10) at administration psilocybin, ketamine and midazolam at 24 hours, 1, 2, 3, 4, 5, 6, 8 and 12 weeks after application.
5. Comparison of time to return of depressive symptoms (defined according to the Criteria for deployment antidepressants, see chapter 6.4) during 12 weeks (3 months) after a single application of psilocybin, ketamine and midazolam.
6. Safety profile of the study medication

Conditions and MedDRA coding

pharmaco-resistant depression

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Men and women over the age of 18
2. Diagnosis of moderate to severe depressive disorder without psychotic symptoms - ICD-10 criteria F32.1-2 or F33.1-2 and MADRS score ≥20
3. The duration of the depressive episode is a minimum of 3 months and a maximum of 2 years
4. treatment-resistant disease defined as: a) Failure of at least 2 and at most 4 adequate treatments (6 weeks of adequate therapeutic doses antidepressants, adequate non-pharmacological procedures, e.g. psychotherapy, neurostimulation treatment, phototherapy, etc.) within the current depressive episode, when using at least 2 antidepressants with a different pharmacological mechanism of action (augmentation is the gate as a second treatment) or in a combination of one pharmacological treatment and 1 non-pharmacological one treatment b) Intolerance of 2 different treatments and 1 adequate treatment or c) Intolerance of 3 different antidepressant treatments.
5. Ability to understand and independently complete all protocol-defined examinations and scales and be present at all study visits
6. Have a secured caregiver who will be able to be in personal contact with the patient 5 times a week
7. Clinical trial participants of childbearing age must agree to use the prescribed methods contraception for the duration of the clinical trial: a) Women - Correct use of a highly reliable contraceptive method, i.e. combined hormonal contraception (in oral, vaginal or transdermal drug form), progestagen hormonal contraceptives associated with inhibition of ovulation (in oral or injectable pharmaceutical form), non-hormonal intrauterine device or intrauterine device releasing hormones, possibly the presence of bilateral tubal occlusion, vasectomy in the partner, or observing sexual abstinence. b) Men – Observing sexual abstinence or using an adequate contraceptive method (i.e. condom) in case of sexual intercourse.

Exclusion criteria 26

1. Severe psychiatric comorbidity (axis I MINI, ICD-10 F0.X – F99.X with the exception of F32.1-2 or F33.1-2, the severity of the disease is clinically assessed by the examining physician)
2. The current depressive phase is severe with psychotic symptoms (ICD-10: F32.2-3, F33.2-3)
3. MADRS suicidality score (item 10) > 4
4. Suicide attempt in the last 6 months
5. Duration of current depressive episode for more than 2 years
6. Current dependence on drugs or alcohol (ICD-10: F17.x) excluding tobacco and excluding abstinence lasting more than 2 years
7. Claustrophobia, inability to undergo MR examination
8. Pregnancy or breastfeeding or plan to become pregnant within the next 3 months
9. Intracranial hypertension, pulmonary hypertension, uncorrected arterial hypertension (BP > 150/100 mmHg)
10. Condition after stroke, myocardial infarction in the last 6 months
11. Heart failure
12. Untreated or decompensated hyperthyroidism
13. Glaucoma
14. Severe respiratory failure or acute respiratory depression
15. History of convulsions
16. Other serious somatic diseases or any other circumstance in which there would be a significant increase of blood pressure posed a serious threat to health (assessed by the examining physician)
17. Pacemaker
18. Metal implants from MR incompatible materials
19. Regular use of medication that could interact with psilocybin (assessed by examining physician)
20. Current use of monoamine oxidase inhibitors (MAOIs). Patients can be included if they will medications with an MAOI effect as part of tapering are completely stopped at least 14 days before V0.
21. Previous experience with psilocybin, hallucinogenic mushrooms or ketamine is possible in maximum 10% of patients. This experience must not be within the last 12 months or within current derpestive episodes.
22. Current medication with antidepressants, antipsychotics or other drugs with a direct antagonist effect on 5-HT2A receptors (e.g. trazodone, mirtazapine, mianserin, risperidone, quetiapine, ketanserin) or interruption of their use less than 7 days before administration of the study medication. Patients can be included, but these drugs must be completely discontinued as part of the tapering for at least 7 days before V0.
23. Electroconvulsive therapy (ECT) in the previous 6 months
24. Repetitive transcranial magnetic stimulation (rTMS) in the previous 4 weeks
25. Daily use of benzodiazepine anxiolytics greater than the equivalent of 10 mg of diazepam
26. Allergy to components of medicinal products

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of fast antidepressant effects of psilocybin versus ketamine.

Secondary endpoints 6

1. Duration of the antidepressant effect of psilocybin, ketamine and midazolam using the MADRS scale during 2 weeks of inpatient stay
2. Duration of the antidepressant effect of psilocybin, ketamine and midazolam after termination of inpatient stay using the MADRS scale.
3. Duration of the antidepressant effect of a single application of psilocybin, ketamine and midazolam using the QIDS scale.
4. Comparison of response rates (50% reduction in MADRS scale) and remissions (MADRS ≤ 10) following psilocybin, ketamine and midazolam treatment
5. Time to reoccurrence of the depressive symptoms within 12 weeks (3 months) after treatment with psilocybin, ketamine and midazolam.
6. Safety profile of study drug: a) acute (vital signs (BP/HR), BPRS, psilocin levels) b) longterm (BPRS, PSQ a Persistent effects scale)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodni Ustav Dusevniho Zdravi

Sponsor organisation

Narodni Ustav Dusevniho Zdravi

Address

Topolova 748

City

Klecany

Postcode

250 67

Country

Czechia

Scientific contact point

Organisation

Narodni Ustav Dusevniho Zdravi

Contact name

Tomáš Páleníček

Public contact point

Organisation

Narodni Ustav Dusevniho Zdravi

Contact name

Nikola Leca

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications