The additive effect of ketamine in combination with electroconvulsive stimulation (ECS) in major depressive disorder (MDD): a translational study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Vita-salute S. Raffaele

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministero della Ricerca e dell'Università - PRIN - 20227EA9AN

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Diagnosis, Therapy

The primary objective of this study is to identify the phenotypic and neurochemical determinants of response to ketamine and electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD).

Secondary objectives 1

1. The primary objective of this study is to identify the phenotypic and neurochemical determinants of response to ketamine and electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD).

Conditions and MedDRA coding

Major Depressive Disorder (MDD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant is willing and able to give informed consent for participation in the study.
2. Male and Female, aged 18-70.
3. Women of childbearing potential (WOCBP) must use at least 1 highly effective method of contraception. Highly effective methods of contraception are those which have a failure rate of <1% (when implemented consistently and correctly) and include: Intrauterine device (IUD), Bilateral tubal ligation, bilateral salpingectomy, or bilateral tubal occlusive procedure, Hormonal contraceptives (eg, oral, patch, or injectable), A double-barrier protection method (eg, condom, sponge, or vaginal diaphragm with spermicide cream, foam, or gel); abstinence from heterosexual intercourse is accepted if this is the participant’s usual lifestyle.
4. Diagnosed with major depressive disorder (according to SCID5-CV scale).
5. Affected by treatment resistant depression (defined as at least 2 different antidepressant agents used without success).
6. Adequacy of the score for anesthesia.

Exclusion criteria 11

1. Chronic neurological disease.
2. Intellectual disability
3. Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurysm, endocrine disorders, neuromuscular diseases, space occupying brain lesions, stroke in the last 6 months),
4. Contraindications to the electroconvulsive therapy (severe aortic valve stenosis, implantable cardiac defibrillators, implantable electronic devises, uncontrolled hypertension, clinically significant respiratory, renal or hepatic disease, abdominal aortic aneurism, endocrine disorders, neuromuscular disease, space-occupying brain lesions, stroke in the last 6 months).
5. Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year,
6. Pregnancy and lactation
7. Cardiovascular conditions
8. Psychiatric Disorders
9. Hepatic impairment
10. Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study
11. Participants with any contraindications to the use of ketamine, such as a history of severe cardiovascular conditions (e.g., uncontrolled hypertension, significant arrhythmias), intracranial hypertension, or severe liver impairment, will also be excluded to prevent potential adverse events.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the mean change in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), from baseline to Day 28 (Week 4). This will assess the short-term efficacy of the treatment.

Secondary endpoints 1

1. The secondary endpoints include the mean change in MADRS scores from baseline to Week 12, which will evaluate the long-term effects of the treatment. Additionally, cognitive outcomes will be assessed at both Day 28 and Week 12 to examine the impact of the treatment on cognitive function.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Vita-salute S. Raffaele

Sponsor organisation

Universita' Vita-salute S. Raffaele

Address

Via Olgettina 58

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Universita' Vita-salute S. Raffaele

Contact name

Danilo De Gregorio

Public contact point

Organisation

Universita' Vita-salute S. Raffaele

Contact name

Danilo De Gregorio

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 19 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