Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
68
Countries
1
Sites
3
Treatment Resistant Depression (TRD)
Compare the effectiveness of psilocybin and personalized rTMS in Treatment Resistant Depression (TRD)
Key facts
- Sponsor
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Psychiatry and Psychology [F] - Mental Disorders [F03]
- Trial duration
- 19 Jan 2026 → ongoing
- Decision date (initial)
- 2025-07-08
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Grant from the Italian Ministry of Health, PNNR 2023 call (project code PNRR-MCNT2-2023-12377068)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
Compare the effectiveness of psilocybin and personalized rTMS in Treatment Resistant Depression (TRD)
Secondary objectives 1
- Explore the different trajectories of antidepressant response associated with psilocybin and personalized rTMS (i.e., impact on the brain networks involved in TRD)
Conditions and MedDRA coding
Treatment Resistant Depression (TRD)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 26.0 | LLT | 10088521 | Treatment resistant depression | 100000004848 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment Intervention Sixty-eight patients with treatment-resistant depression (TRD) will be randomly assigned to two intervention arms (34 patients per group) in a double-blind, randomized controlled, non-inferiority trial.
Both groups will receive an active intervention and a placebo corresponding to the other intervention, in a double dummy design. The trial aims to compare the effectiveness of psilocybin (PSILO group) and a neuromodulation intervention (rTMS group) as the active comparator.
|
Randomised Controlled | Double | [{"id":157886,"code":2,"name":"Investigator"},{"id":157890,"code":1,"name":"Subject"},{"id":157889,"code":3,"name":"Monitor"},{"id":157887,"code":5,"name":"Carer"},{"id":157888,"code":4,"name":"Analyst"}] | PSILO group: The patients will receive 2 doses of 25 mg of psilocybin (on days 1 and 22). Additionally, they will receive sham rTMS stimulation for one week from day 4 to day 8. rTMS group: The patients will undergo 10 daily sessions of rTMS for five days (from day 4 to day 8). Each session will use Intermittent Theta Burst Stimulation (iTBS), with a duration of five minutes. All patients will receive placebo psilocybin capsules on days 1 and 22. |
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- N/A
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-519844-34-01 | Advancing PRecise Interventions for resistant DEpression: rebalancing brain networks and investigating the trajectories of antidepressant effect with non-psychedelic psilocybin and personalized neuromodulation (PRIDE) | Universita' Degli Studi G. D'Annunzio Di Chieti |
| 2024-519844-34-02 | Advancing PRecise Interventions for resistant DEpression: rebalancing brain networks and investigating the trajectories of antidepressant effect with non-psychedelic psilocybin and personalized neuromodulation (PRIDE) | Universita' Degli Studi G. D'Annunzio Di Chieti |
| 2024-519844-34-00 | Advancing PRecise Interventions for resistant DEpression: rebalancing brain networks and investigating the trajectories of antidepressant effect with non-psychedelic psilocybin and personalized neuromodulation (PRIDE) | Universita' Degli Studi G. D'Annunzio Di Chieti |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Age between 18 and 65 years
- Diagnosis of TRD: subjects with a MDD diagnosis, non-responders to at least two antidepressant medications at adequate doses administered for adequate time (i.e., 4-6 weeks)
Exclusion criteria 6
- Presence of severe organic/neurological comorbidities
- Previous episodes of seizures
- Substance use disorders
- Cognitive decline
- Psychotic disorders
- Pregnancy/postpartum state
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Non-inferiority (with a 25% margin) in terms of percentage of clinical responders, defined as the reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores ≥ 50%, after 60 days from the start of the trial.
Secondary endpoints 10
- Hamilton Anxiety Rating Scale (HAM-A) score
- Hamilton Depression Rating Scale (HAM-D) score
- Brief Psychiatric Rating Scale (BPRS) score
- Young Mania Rating Scale (YMRS) score
- Snaith-Hamilton Pleasure Scale (SHAPS) scores for anhedonia
- Columbia–Suicide Severity Rating Scale and Beck Hopelessness Scale scores for suicide risk
- Trail Making Test for attention and executive functions
- Clinical Global Impression Severity (CGIS) and Health Status Questionnaire scores for impact of symptoms on health
- Functional magnetic resonance imaging (fMRI) analysis for changes in connectivity patterns in TRD-related brain networks
- Electroencephalography (EEG) for changes in functional connectivity
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PEX010 Psilocybin Capsules (25mg psilocybin)
PRD11829228 · Product
- Active substance
- Dry Extract From Psilocybe Cubensis (15-25:1), Extraction Solvent: Methanol
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 50 mg milligram(s)
- Max treatment duration
- 3 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- UNIVERSITA' DEGLI STUDI G. D'ANNUNZIO DI CHIETI
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
PCB2 (inert placebo containing maltodextrin)
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universita' Degli Studi G. D'Annunzio Di Chieti
- Sponsor organisation
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Address
- Via Luigi Polacchi 11
- City
- Chieti Scalo
- Postcode
- 66100
- Country
- Italy
Scientific contact point
- Organisation
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Contact name
- Clinical trial scientific information point
Public contact point
- Organisation
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Contact name
- Clinical trial information desk
Sponsor responsibilities
- Article 77 compliance
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Contact point sponsor
- Universita' Degli Studi G. D'Annunzio Di Chieti
- Article 77 implementation
- Universita' Degli Studi G. D'Annunzio Di Chieti
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 68 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Universita' Degli Studi G. D'Annunzio Di Chieti
Department of Neurosciences, Imaging, and Clinical Sciences, Via Luigi Polacchi 11, 66100, Chieti Scalo
Azienda Ospedaliero Universitaria - Policlinico Riuniti Foggia
Unit of Psychiatry, Viale Pinto 1, 71122, Foggia
ASL Roma 5
Department of Psychiatry, Via degli Esplosivi 9, 00034, Colleferro (RM)
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2026-01-19 | 2026-01-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol_rev-rev_clean copy | 6 |
| Recruitment arrangements (for publication) | Recruitment arrangements | 3 |
| Subject information and informed consent form (for publication) | Consenso al trattamento dei dati personali | 3 |
| Subject information and informed consent form (for publication) | Foglio informativo-Modulo consenso | 3 |
| Subject information and informed consent form (for publication) | Lettera per il medico di libera scelta | 3 |
| Subject information and informed consent form (for publication) | Rimborso spese | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | Summary of Product Characteristics-SmPC | 1 |
| Synopsis of the protocol (for publication) | Sinossi_IT | 3 |
| Synopsis of the protocol (for publication) | Synopsis_EN | 3 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-04-28 | Italy | Acceptable 2025-06-30
|
2025-07-08 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-10 | Italy | Acceptable 2025-06-30
|
2025-08-10 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-11-19 | Italy | Acceptable 2025-06-30
|
2025-11-19 |