Evaluation of p-glycoprotein alterations in treatment-resistant depression: a [18F]MC225 PET study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

14 Jul 2025 → ongoing

Decision date (initial)

2025-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministry of Health (GR-2021-12374141)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

The primary aim of the study is to assess the involvement of P-gp in TRD by PET/CT, using [18F]MC225 as a radiotracer, by comparing P-gp activity in subjects with TRD and in subjects with treatment respondent depression (DRESP). P-gp activity will be assessed by measuring [18F]MC225 standardized uptake value (SUV) volume distribution (VD) in the whole brain.

Secondary objectives 1

1. P-gp activity will be also assessed by measuring [18F]MC225 standardized uptake value (SUV) and volume distribution (VD) in 9 VOIs per latus. In subjects with TRD, we will further assess the potential relationship between P-gp activity and clinical characteristics related to illness severity, i.e., duration of disease, number of episodes, number of previous attempted suicides, current episodes of attempted suicide, previous psychosis, current psychosis, previous drug abuse, previous pharmacotherapy.

Conditions and MedDRA coding

depression

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age between 18 and 65 years old
2. MDD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorder, 5th edition (DSM-5)
3. At least 5 years of education
4. Capability of completing imaging procedures
5. Presence of a current TRD will be additionally required for TRD subjects, according to the most-commonly described criteria used by studies/guidelines for TRD, namely: nonresponse to a minimum of two prior antidepressant treatment attempts of an adequate dose and duration. Non-response will be defined as failure of an antidepressant treatment to induce symptoms remission, according to the NH-mental health study STAR D and experts definition. Treatment resistance/response in the last/current episode should not involve antidepressant which have been proven not to be substrates of P-gp
6. Capability of providing written informed consent

Exclusion criteria 13

1. Age <18 years and > 65 years old
2. Presence of drug and alcohol abuse/dependence during the last 6 years
3. Additional psychiatric disorders
4. Neurological or major medical illnesses
5. Dementia or mild cognitive impairment
6. Traumatic brain injury with loss of consciousness
7. Any brain abnormality or microvascular lesions
8. Pregnancy, breastfeeding, or intention to undergo pregnancy within 6 months from the PET/CT scan
9. Inability to provide written informed consent
10. Absence of adequate visual and auditory acquity to perform imaging procedures
11. Claustrophobia and/or inability to tolerate brain PET acquisition that would have an impact on the collection of a good quality scan
12. Poor peripheral arterial and/or venus access that would interfere with radiopharmaceutical administration and/or blood sampling
13. Use of medications with a known effect to P-gp activity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess between groups differences as for whole-brain DV and SUV of [18F]MC225 (outcome variables) in TRD and DRESP. Overall SUV and DV will be computed as the sum of the 18 VOIs.

Secondary endpoints 3

1. To assess between groups differences as for DV and SUV of [18F]MC225 in each VOI, both on the right and left latus, in TRD and DRESP
2. (specifically in TRD subjects) To assess the relationship between [18F]MC225 DV and SUV on the whole brain, and clinical parameters related to the severity of the disease (i.e. duration of disease, number of episodes, number of previous attempted suicides, current episode of attempted suicide, previous psychosis, current psychosis, previous drug abuse, previous pharmacotherapy)
3. (specifically in TRD subjects) To assess the relationship between [18F]MC225 DV and SUV at the level of each VOI, either left or right, and the aforementioned clinical parameters related to the severity of the disease

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Alessio Simonetti

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Alessio Simonetti

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 15 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