Comparing Ketamine and Placebo for Severe Depression Treatment

Early Efficacy of Ketamine Compared With Placebo as Adjunctive Therapy With Venlafaxine in Severely Unipolar Depressed Inpatients

This study tests if intravenous ketamine can help people with severe depression feel better faster than traditional antidepressants.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 4 sites (Le Kremlin-Bicêtre, France and 3 other locations)
• Trial ID: NCT06508710 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the early effects of intravenous ketamine compared to a placebo in patients experiencing severe major depressive episodes. The study aims to assess the efficacy of ketamine in improving symptoms more rapidly than traditional antidepressants, which typically take weeks to show effects. Participants will be hospitalized and monitored closely, with the potential for PET imaging to evaluate changes in synaptic density in the brain. The trial focuses on patients who are candidates for venlafaxine treatment, providing a comprehensive approach to managing severe depression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a current major depressive episode and a high severity score, who are hospitalized and eligible for venlafaxine treatment.

Not a fit: Patients with treatment-resistant depression or those with specific associated pathologies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to faster relief from severe depression symptoms, reducing the need for prolonged hospitalization.

How similar studies have performed: Previous studies have shown promising results for ketamine in treatment-resistant depression, suggesting potential success for this approach in non-resistant cases.

Eligibility criteria

Inclusion Criteria:

* Current MDE in the context of unipolar major depressive disorder (DSM-5 criteria), hospitalized (open care) for this episode, with a minimum HDRS score of 24 and in the context of an indication for the introduction of venlafaxine treatment.
* Patient aged between 18 and 65.
* Signed free and informed consent
* Membership of a social security scheme
* For women of childbearing age, effective contraception throughout study participation.\* (\*Combined hormonal contraception (containing estrogen and progestin) associated with ovulation inhibition: (oral, intravaginal, transdermal), Progestin-only hormonal contraception associated with ovulation inhibition: (oral, injectable, implantable), Intrauterine device (IUD), Hormonal intrauterine system (IUS), Bilateral tubal occlusion, Vasectomized partner, Sexual abstinence.)

Exclusion Criteria:

* Criteria relating to associated pathologies entailing particular risks: pharmaco-resistant CDE (failure of at least two properly conducted treatments with two different antidepressant treatment classes), CDE with psychotic features, psychotic disorder, bipolar disorder, current (\<1 month) substance use disorder (excluding tobacco).
* Liver impairment (AST and/or ALT \> 3 ULN, PAL and/or GGT and/or bilirubin \> 2 ULN).
* Severe renal insufficiency (GFR \<30ml/min with Cockcroft's formula).
* Bradycardia less than 55 beats per minute.
* Contraindication to ketamine : Hypersensitivity to active substance or excipients, comatose state, central nervous system (CNS) depression, Parkinson's disease, Lewy body dementia, progressive supranuclear palsy, known prolongation of the QTc interval (\>450ms for men and \>470ms for women) or congenital long QT syndrome, recent acute myocardial infarction, uncompensated heart failure, history of ventricular arrhythmias or torsades de pointes, uncorrected hypokalemia (K+ \< 3. 5 mmol/l), epilepsy, uncontrolled hypertension, porphyria, history of stroke (CVA), intracranial hypertension.
* Contraindication to venlafaxine (hypersensitivity to venlafaxine or excipients, are hereditary conditions of fructose intolerance, glucose-galactose malabsorption syndrome, or sucrase-isomaltase deficiency, unstable hypertension, no indication for venlafaxine treatment in clinician's opinion due to ineffectiveness or tolerability of previous venlafaxine treatment).
* Current or previous treatment with venlafaxine or ketamine in the month prior to study inclusion.
* Need to maintain another antidepressant, MAOI, Millepertuis or benzodiazepines (cyamemazine is permitted). Or potential drug interactions in case of recent cessation of these treatments (based on the Summary of Product Characteristics (SmPC) of the respective medication(s) and their half-life).
* Any other unspecified reason (clinically significant illness or anomaly) which, in the opinion of the investigator or the sponsor, could compromise the safety of the participant.
* Pregnant or breast-feeding patients (women of childbearing potential must have a negative urine or blood test for human chorionic gonadotropin prior to trial entry). Planned pregnancy within three months of enrolment
* Adult under guardianship, curatorship or safeguard of justice
* Participating in other interventional research involving the human body or within the exclusion period following previous research involving the human body, if applicable.
* Social insurance

Additional criteria for inclusion in the ancillary study :

\- Contraindications to \[11C\]UCB-J PET-MRI

1. Absolute contraindications: Pacemaker or neurosensorial stimulator or implantable defibrillator; clip on a brain aneurysm or vascular malformation; intraocular or intracerebral ferromagnetic foreign body; prostheses or objects or mobile ferromagnetic metal fragments; cochlear implants; peripheral stimulator; neurosurgical ventriculoperitoneal shunt valves; automated injection device such as insulin pump, glucose sensor; permanent eyelid or lip makeup; non-removable piercing; claustrophobia.
2. Relative contraindications: Dental prostheses and orthodontic material; certain intrauterine devices; certain tattoos; certain transdermal patch implants; certain metal implants far from the examined area. (The investigator physician and/or radiology operator will always conduct a precise questionnaire before the examination to ensure perfect safety and absence of MRI danger)

Where this trial is running

Le Kremlin-Bicêtre, France and 3 other locations

• Psychiatry unit — Le Kremlin-Bicêtre, France, France (Recruiting)
• EPS Barthélémy Durand — Étampes, France (Not_yet_recruiting)
• Bicetre Hospital - CRC — Le Kremlin-Bicêtre, France (Not_yet_recruiting)
• Cea/shfj — Orsay, France (Active_not_recruiting)

Study contacts

• Principal investigator: Romain COLLE — Service Hospitalo-Universitaire de Psychiatrie - Hôpital Bicêtre
• Study coordinator: Romain COLLE

Conditions Major Depressive Episode; depression; ketamine; synaptogenesis