Effect of psilocybin on the positive valence system in treatment-resistant depression: a pilot clinical neuroimaging study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

5 Nov 2024 → 26 Sep 2025

Decision date (initial)

2024-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

chu nimes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Comparing the activity of neural circuits responsible for effort assessment before and after psilocybin administration

Secondary objectives 4

1. To evaluate the effect of single-dose psilocybin administration, accompanied by a caregiver, on treatment-resistant depression (TRD) at the inclusion visit, 4 days, 1 month and 3 months.
2. Assess change in anhedonia and behavioral activation scores following treatment at inclusion visit, 4 days, 1 month and 3 months
3. Studying the acceptability and feasibility of a clinical protocol for augmented therapy with psilocybin
4. Examine the effect of psilocybin treatment on states of consciousness.

Conditions and MedDRA coding

depression

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient with a DSM-IV diagnosis of a current moderate or severe depressive episode without psychotic features (based on clinical assessment and confirmed by MINI interview and QIDS).
2. Patient who has failed to respond to at least 2 sequences of treatment with antidepressants of different classes at the minimum effective dose lasting at least 6 weeks.
3. Patient with a score > 10 on the QIDS scale.
4. Patient aged ≥ 25 years and < 60 years.
5. Patient available for 6-month follow-up.
6. Good physical health and absence of unstable medical pathology. These pathologies include cardiovascular comorbidities: history of stroke, myocardial infarction, heart failure, arrhythmia, uncontrolled hypertension (greater than 165/95 mmHg at screening); organic epileptic syndrome and active neurological comorbidities; endocrine pathologies (dysthyroidism and adrenal insufficiency, type I diabetes or insulin-requiring type II diabetes, history of severe hypoglycemia requiring hospital treatment); significant impairment of liver function; glaucoma; symptomatic prostate hypertrophy or bladder neck obstruction.
7. Patient able to speak and understand French easily.
8. Patient has given free and informed consent.
9. Patient has signed consent form.
10. Patient affiliated to or benefiting from a health insurance

Exclusion criteria 29

1. Patient at moderate or severe risk of suicide according to clinical judgment (based on the MINI suicidality module).
2. Patients at high risk of adverse emotional or behavioral reactions according to the investigator's clinical assessment (e.g. severe personality disorder, antisocial behavior, severe current stressors, lack of significant social support or any psychotic symptoms identified during interviews).
3. Active substance dependence according to the MINI questionnaire (excluding tobacco).
4. Patients whose psychotropic treatment (anxiolytics, antipsychotics, hypnotics, mood regulators) has been modified in the last month.
5. Patients with intellectual disabilities (IQ less than or equal to 75).
6. Patients with a lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder or psychosis not otherwise specified.
7. Patients with a family history of schizophrenia, schizoaffective disorder or type 1 bipolar disorder in first- or second-degree relatives.
8. Subjects participating in psychotherapy during the study.
9. Patients with any unstable disease or physical condition as determined by clinical examination, history or laboratory tests (ECG, blood work at inclusion) Unstable physical conditions include: presence of fever or inflammatory syndrome, unstabilized hypertension or > 180/100, class IV heart failure, respiratory, hepatic or renal failure, and history of stroke, intracranial hypertension or epilepsy under treatment.
10. Patients with contraindications to magnetic resonance imaging
11. Patients with allergy, hypersensitivity or other adverse reaction to previous use of psilocybin or other hallucinogens.
12. Patients who have used hallucinogenic substances (excluding cannabis) more than 5 times in their lifetime or at any time in the last two months.
13. Patients on medication or illicit substances likely to interfere with the effects of psychedelics (urinalysis and breathalyser on D0).
14. Patient with regular consumption of alcoholic beverages (>20 drinks/week)
15. Any other major clinically significant concomitant disease which, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk to the participant, should he/she participate in the study.
16. Patients with a prolonged QTc interval (>450 ms for men and >470 ms for women).
17. Participant planning to donate sperm within three months of psilocybin administration.
18. Participants having sexual relations that could lead to pregnancy and who do not agree to use a highly effective contraceptive method (contraceptive ring, surgical contraception, implant, patch, contraceptive pill, male and female condoms, IUD) throughout their participation in the study and for at least three months after psilocybin administration.
19. Positive serum pregnancy test at inclusion for participants of childbearing age. NB: serum pregnancy test will be performed on the day of psilocybin administration.
20. Pregnant (confirmed by pregnancy test), parturient or breast-feeding patient, or patient wishing to become pregnant during the study period.
21. Patient already participating in an interventional drug study
22. Patient in exclusion period determined by another study.
23. Patients under court protection, guardianship or curatorship, or under a non-consensual care measure.
24. Patient unable to give consent.
25. Patient for whom it is impossible to give informed information.
26. Patient with positive pregnancy test prior to psilocybin administration
27. Any patient who was hospitalized as an outpatient or inpatient between the date of inclusion and the administration of psilocybin.
28. Any patient with a confirmed, interrupted or aborted suicide attempt between the date of inclusion and psilocybin administration.
29. Any patient who expressed suicidal ideation associated with the planning of a suicidal act (active suicidal ideation) between the date of inclusion and the administration of psilocybin.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Brain activity measured by fMRI in regions involved in effort assessment before and after treatment: basolateral amygdala, dorsal anterior cingulate cortex, ventral pallidum, ventral striatum, ventral tegmental area

Secondary endpoints 4

1. Delta depression scores before & after treatment (Quick Inventory of Depressive Symptomatology, Clinician Rated and Self-report) at inclusion visit, 4 days, 1 month and 3 months.
2. Delta of Behavioral Activation for Depression Scale (BADS) and Snaith-Hamilton Pleasure Scale (SHAPS) scores before and after treatment.
3. Evaluation of therapy administration sessions by patients: satisfaction, number and severity of adverse events or tolerance problems reported.
4. 5-Dimensional Altered States of Consciousness Questionnaire score.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

4 Place Du Professeur Robert Debre

City

Nimes Cedex 9

Postcode

30029

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

leonie gazel

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 10 files

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

Application history

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