Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboRecruiting

Early Effects of Ketamine vs Placebo With Venlafaxine in Severe Depression Patients (MOODBOOSTER)

This randomised, quadruple-blind, placebo-controlled Phase III trial (n=60) will study the early effects of ketamine compared to placebo as an adjunctive therapy with venlafaxine in inpatients with severe unipolar major depressive disorder (MDD).

Target Enrollment
60 participants
Study Type
Phase III interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomised, quadruple-blind, parallel-group Phase III trial in hospitalized adults with severe unipolar MDE (HDRS ≥24) comparing three IV ketamine infusions (0.5 mg/kg on Days 1, 4 and 7) versus matching saline placebo, both given adjunctive to venlafaxine.

Primary aim is to assess early antidepressant effects and safety; an ancillary PET-MRI study using [11C]UCB-J will assess synaptic density changes in a subset, with additional imaging-specific eligibility criteria.

Study Protocol

Preparation

sessions

Dosing

3 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Ketamine + venlafaxine

experimental

Three IV ketamine infusions (Days 1, 4, 7) given adjunctive to usual venlafaxine treatment.

Interventions

  • Ketamine0.5 mg/kg
    via IV• three doses (Days 1,4,7)• 3 doses total

    Adjunctive to venlafaxine

Placebo + venlafaxine

placebo

Three IV placebo infusions (0.9% NaCl, 50 mL) given adjunctive to venlafaxine.

Interventions

  • Placebo
    via IV• three doses (Days 1,4,7)• 3 doses total

    50 mL NaCl 0.9% per infusion; adjunctive to venlafaxine

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion 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.)
  • 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)

Exclusion Criteria

  • 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

Study Details

Locations

Psychiatry unit — Le Kremlin-Bicêtre, France, France
EPS Barthélémy Durand — Étampes, France
Bicetre Hospital - CRC — Le Kremlin-Bicêtre, France
CEA/SHFJ — Orsay, France

Your Library