NCT07088380

Brief Summary

This is a randomized, double-blind, placebo-controlled phase 3 clinical trial evaluating the additive effect of intravenous ketamine in combination with electroconvulsive therapy (ECT) in patients with treatment-resistant major depressive disorder (MDD). The study aims to determine whether ketamine enhances the antidepressant efficacy of ECT and reduces associated cognitive side effects. Thirty hospitalized patients diagnosed with treatment-resistant MDD will be randomized to receive either ketamine or placebo (saline) during ECT sessions 2, 4, and 6. Primary outcome is the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4 weeks.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at below P25 for phase_3 major-depressive-disorder

Timeline
Completed

Started Jul 2025

Shorter than P25 for phase_3 major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 8, 2025

Completed
2 days until next milestone

Study Start

First participant enrolled

July 10, 2025

Completed
18 days until next milestone

First Posted

Study publicly available on registry

July 28, 2025

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2026

Completed
Last Updated

July 29, 2025

Status Verified

July 1, 2025

Enrollment Period

7 months

First QC Date

July 8, 2025

Last Update Submit

July 27, 2025

Conditions

Major Depressive DisorderTreatment Resistant Depression

Keywords

ketamineTRDdepressionelectroconvulsive therapy (ECT)

Outcome Measures

Primary Outcomes (1)

  • Mean change in depressive symptoms, as measured by MADRS scale

    The primary efficacy endpoint will be assessed using the MADRS score (Montgomery-Åsberg Depression Rating Scale)

    From baseline (day 0) to day 28 (7 days after the last ECT session). A follow-up assessment at Week 12 (90 days) will be included

Secondary Outcomes (5)

  • Change in Suicidal Ideation (Beck Scale for Suicide Ideation - BSSI)

    Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)

  • Change in Anxiety Symptoms (Hamilton Anxiety Rating Scale - HAM-A)

    Assessment will be performed at: baseline (day 0); Weekly during ECT treatment period (Weeks 1, 2, 3); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)

  • Change in Cognitive Function (Brief Assessment of Cognition in Affective Disorders - BAC-A)

    Assessment will be performed at: baseline (day 0); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT session)

  • Change in Dissociative and Psychotic Symptoms (Clinician-Administered Dissociative States Scale - CADSS; Brief Psychiatric Rating Scale - BPRS)

    Assessment will be performed at: Baseline (Day 0, before first ECT session); Week 1 (After ECT session 2); Week 2 (After ECT session 4); Week 3 (After ECT session 6); Week 4 (1 week after last ECT session); Follow-up: Week 12 (3 months after last ECT

  • Change in Neurochemical Markers (Plasma Levels of Trp, 5-HT, 5-HIAA, Glutamate, Aspartate)

    Assessment will be performed at: Baseline (Day 0, before first ECT session); Weekly during ECT treatment period (Weeks 1, 2, 3)

Study Arms (2)

Ketamine

EXPERIMENTAL

Patients receive standard ECT treatment combined with intravenous ketamine at a subanesthetic dose of 0.5 mg/kg, administered after induction with Propofol. Ketamine is administered during ECT sessions 2, 4, and 6. Intervention: * Drug: Ketamine * Dose: 0.5 mg/kg IV * Timing: ECT sessions 2, 4, and 6 * Background: Investigating the additive antidepressant and potential cognitive-protective effects of ketamine in patients with treatment-resistant depression undergoing ECT.

Drug: Ketamine Hydrochloride

Placebo

PLACEBO COMPARATOR

Patients receive standard ECT treatment combined with placebo (0.9% sodium chloride solution), administered intravenously after induction with Propofol, during ECT sessions 2, 4, and 6, mimicking the ketamine group's schedule. Intervention: * Drug: Saline solution (NaCl 0.9%) * Timing: ECT sessions 2, 4, and 6 * Background: Serves as control to assess the specific contribution of ketamine to antidepressant efficacy and cognitive outcomes.

Drug: Placebo

Interventions

Ketamine HydrochlorideDRUG

Ketamine will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.

Ketamine
PlaceboDRUG

Placebo will be administered intravenously at a subanesthetic dose of 0.5 mg/kg after a bolus of Propofol, during ECT sessions 2, 4, and 6.

Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male and female subjects ages 18-70,
  • diagnosed with MDD (according to SCID5-CV interview)
  • treatment resistant (defined as at least 2 different antidepressant agents used without success),
  • ability to give informed consent,
  • adequacy of the score for anesthesia.

You may not qualify if:

  • Chronic neurological diseases,
  • Intellectual disability
  • 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),
  • Patients with Alcohol Use Disorder or Substance Use Disorder or Substance Abuse history in the past year,
  • Pregnancy and lactation
  • Cardiovascular conditions,
  • Psychiatric Disorders,
  • Hepatic impairment,
  • Participants with a known hypersensitivity to ketamine or any of its excipients will be excluded from the study,
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS Ospedale San Raffaele Turro

Milan, 20127, Italy

RECRUITING

Related Publications (4)

  • Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evid Based Ment Health. 2016 May;19(2):35-8. doi: 10.1136/eb-2016-102355. Epub 2016 Apr 6.

    PMID: 27053196BACKGROUND

  • Anderson IM, Blamire A, Branton T, Clark R, Downey D, Dunn G, Easton A, Elliott R, Elwell C, Hayden K, Holland F, Karim S, Loo C, Lowe J, Nair R, Oakley T, Prakash A, Sharma PK, Williams SR, McAllister-Williams RH; Ketamine-ECT Study team. Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial. Lancet Psychiatry. 2017 May;4(5):365-377. doi: 10.1016/S2215-0366(17)30077-9. Epub 2017 Mar 27.

    PMID: 28359862BACKGROUND

  • Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI. Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Mol Psychiatry. 2020 Jul;25(7):1592-1603. doi: 10.1038/s41380-018-0256-5. Epub 2018 Oct 3.

    PMID: 30283029BACKGROUND

  • Nuzzi M, Delmonte D, Barbini B, Pasin L, Sottocorna O, Casiraghi GM, Colombo C, Landoni G, Zangrillo A. Thiopental is better than propofol for electroconvulsive therapy. Acta Biomed. 2018 Jan 16;88(4):450-456. doi: 10.23750/abm.v88i4.6094.

    PMID: 29350659BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, MajorDepressive Disorder, Treatment-ResistantDepression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Alberto AZ Zangrillo, MD

    Università Vita-Salute San Raffaele

    PRINCIPAL INVESTIGATOR

  • Cristina CC Colombo, MD

    IRCCS Ospedale San Raffaele Turro

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alberto AZ Zangrillo, MD

CONTACT

0226436154zangrillo.alberto@hsr.it

Cristina CC Colombo, MD

CONTACT

0226435278colombo.cristina@hsr.it

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, Full Professor

Study Record Dates

First Submitted

July 8, 2025

First Posted

July 28, 2025

Study Start

July 10, 2025

Primary Completion

February 1, 2026

Study Completion

February 1, 2026

Last Updated

July 29, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)