Early Effects of Ketamine vs Placebo With Venlafaxine in Severe Depression Patients
NCT Number: NCT06508710
Acronym: MOODBOOSTER
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Major Depressive Episode
Interventions: DRUG: Ketamine|DRUG: Placebo
Sponsor: Assistance Publique - Hôpitaux de Paris
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2026-04
Locations: Bicetre Hospital - CRC, Le Kremlin-Bicêtre, 94250, France|CEA/SHFJ, Orsay, 94401, France|EPS Barthélémy Durand, Étampes, 91152, France

Summary:
Unipolar major depressive disorder is the leading cause of disability worldwide. The most commonly used treatments for major depressive episodes (MDE) are antidepressant medications. However, they have limited efficacy and their onset of action is long, ranging between 2 to 6 weeks. During this period, hospitalization can become necessary, especially for severe MDE. It is crucial to improve the early effectiveness of treatments for these patients in order to alleviate their suffering, limit complications (suicidal risk), and reduce hospitalization durations (approximately 1000 euros per day). The efficacy of intravenous ketamine has been demonstrated in pharmaco-resistant depression but remains to be proven in non-pharmaco-resistant severe MDE. Additionally, PET imaging using \[11C\]UCB-J, which allows the in vivo study of synaptic density in the human brain, has shown significant decreases in synaptic density in unipolar patients with severe MDE. Furthermore, a single ketamine infusion was found to enhance synaptogenesis

Primary Outcome Measures: the early efficacy on depressive symptomatology, Evolution of the total score of the Hamilton Depression Rating Scale (HDRS 17 items: scale items are rated from 0 to 2 or from 0 to 4 and the score ranges from 0 to 52) after 7 days of treatment by venlafaxine The HDRS scale will be assessed by a senior psychiatrist or psychologist trained in administering the scales, following a psychiatric interview, at day 0 and day 7
Secondary Outcome Measures: The efficacy of ketamine on HDRS overall score, To compare the efficacy of ketamine as adjunctive therapy, after the early adjunctive treatment phase, and placebo, by assessing changes in overall score obtained on the HDRS 17-items., at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine|The efficacy of Ketamine on HDRS response rate, To compare the efficacy of ketamine as adjunctive therapy, after the early adjunctive treatment phase, and placebo, by assessing HDRS response rate (improvement of 50% or more in the overall HDRS score) between groups, at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine|The efficacy of Ketamine on HDRS remission rate, at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine, To compare the efficacy of ketamine as adjunctive therapy, after the early adjunctive treatment phase, and placebo, by assessing remission rate (HDRS 17 items ≤ 7) between groups|The efficacy of ketamine on BDI overall score, To compare the efficacy of ketamine as adjunctive therapy, after the early adjunctive treatment phase, and placebo, by assessing changes in overall score obtained on the short form of the Beck Depression Inventory (BDI), at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine|The efficacy of ketamine on CGI scale, To compare the efficacy of ketamine as adjunctive therapy, after the early adjunctive treatment phase, and placebo, by assessing changes in Clinical Global Impression (CGI) scale, at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine|Duration of hospitalization, Evaluate whether ketamine as adjunctive therapy reduces the length of hospital stay, noting the number of days spent in hospital (including re-hospitalization) The discharge from hospitalization will be decided by the treatment-blinded clinician responsible for the patient, 42 days|Reduction of suicidal ideation, Evaluate whether adjunctive ketamine reduces early suicidal ideation, by assessement of overall Columbia-Suicide Severity Rating Scale (C-SSRS) score, after 7 days of treatment by venlafaxine, at day 0 and day 7|Clinical improvement on HDRS overall score, Evaluate whether ultra-early improvement (at D1 or D4 of treatment by venlafaxine) predicts clinical improvement at D7, D14, D28 and D42 by tracking changes in overall score obtained on the 17-item Hamilton Depression Rating Scale (HDRS), at day 7, 14, 28 and 42|Clinical improvement on HDRS response rate, Evaluate whether ultra-early improvement (at D1 or D4 of treatment by venlafaxine) predicts clinical improvement at D7, D14, D28 and D42 by tracking HDRS response rate (improvement of 50% or more in the overall HDRS score), at day 7, 14, 28 and 42|Clinical improvement on HDRS remission rate, Evaluate whether ultra-early improvement (at D1 or D4 of treatment by venlafaxine) predicts clinical improvement at D7, D14, D28 and D42 by tracking remission rate (HDRS 17 items ≤ 7), at day 7, 14, 28 and 42|Clinical improvement on BDI overall score, Evaluate whether ultra-early improvement (at D1 or D4 of treatment by venlafaxine) predicts clinical improvement at D7, D14, D28 and D42 by tracking changes in overall score obtained on the short form of the Beck Depression Inventory (BDI), at day 7, 14, 28 and 42|Clinical improvement on CGI scale, Evaluate whether ultra-early improvement (at D1 or D4 of treatment by venlafaxine) predicts clinical improvement at D7, D14, D28 and D42 by tracking changes in Clinical Global Impression (CGI) scale, at day 7, 14, 28 and 42|Tolerance on blood pressure, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes post-infusion of treatment or placebo on blood pressure, Day 1, 4, 7|Tolerance on heart rate, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes after infusion of treatment or placebo on heart rate., Day 1, 4, 7|Tolerance on respiratory rate, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes after infusion of treatment or placebo on respiratory rate, Day 1, 4, 7|Tolerance on nausea and vomiting, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes after infusion of treatment or placebo on nausea/vomiting, Day 1, 4, 7|Tolerance on dissociation, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes after infusion of treatment or placebo on dissociation, Day 1, 4, 7|Tolerance on headaches, Tolerance will be assessed according to CTCAE grade (version 5.0), with special monitoring of the effects of ketamine during and up to 40 minutes after infusion of treatment or placebo on headaches, Day 1, 4, 7|The consumption of anxiolytic treatments, cumulative consumption in mg of cyamemazine will be recorded over the entire study period, During all the study|Biomarkers, Identify biomarkers predictive or associated with the efficacy of venlafaxine associated with ketamine, Day 1 and 14
Other Outcome Measures: Synaptic density variation in the whole brain, Within-subject variation in synaptic density between day 0 and day 14 following treatment initiation of venlafaxine, estimated by measuring the rate of \[11C\]UCB-J binding to SV2A proteins by PET-MRI in the whole brain, Day 0 and 14|synaptic density variation in the cingulate cortex, Within-subject variation in synaptic density between day 0 and day 14 following treatment initiation of venlafaxine, estimated by measuring the rate of \[11C\]UCB-J binding to SV2A proteins by PET-MRI in the cingulate cortex, Day 0 and 14|synaptic density variation in the prefrontal cortex, Within-subject variation in synaptic density between day 0 and day 14 following treatment initiation of venlafaxine, estimated by measuring the rate of \[11C\]UCB-J binding to SV2A proteins by PET-MRI in the prefrontal cortex, Day 0 and 14|synaptic density variation in the hippocampus, Within-subject variation in synaptic density between day 0 and day 14 following treatment initiation of venlafaxine, estimated by measuring the rate of \[11C\]UCB-J binding to SV2A proteins by PET-MRI in the hippocampus, Day 0 and 14|Relationship between ketamine efficacy and synaptogenesis, Correlation between changes in the HDRS scale and within-subject variation in synaptic density between day 0 and day 14 following treatment initiation of venlafaxine., Day 0 and 14