NCT06508710招募中3 期
Early Efficacy of Ketamine Compared With Placebo as Adjunctive Therapy With Venlafaxine in Severely Unipolar Depressed Inpatients
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- the early efficacy on depressive symptomatology
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.)
排除标准
- •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+ <
- •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
- •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.
- •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)
研究组 & 干预措施
Ketamine Group
Experimental
The patient will receive 3 doses of intravenous ketamine (0,50mg/kg) in addition to the usual venlafaxine treatment
干预措施: Ketamine (Drug)
Placebo group
Placebo Comparator
The patient will receive 3 doses of intravenous placebo (50mL of NaCl 9‰) in addition to the usual venlafaxine treatment
干预措施: Placebo (Drug)
结局指标
主要结局
the early efficacy on depressive symptomatology
时间窗: at day 0 and day 7
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
次要结局
- The efficacy of Ketamine on HDRS response rate(at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine)
- The efficacy of ketamine on BDI overall score(at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine)
- The efficacy of ketamine on HDRS overall score(at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine)
- The efficacy of Ketamine on HDRS remission rate(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 CGI scale(at day 1,4,7,14, 28 and 42 following the initiation of treatment by venlafaxine)
- Clinical improvement on CGI scale(at day 7, 14, 28 and 42)
- Tolerance on blood pressure(Day 1, 4, 7)
- Tolerance on heart rate(Day 1, 4, 7)
- Tolerance on respiratory rate(Day 1, 4, 7)
- Tolerance on nausea and vomiting(Day 1, 4, 7)
- Tolerance on headaches(Day 1, 4, 7)
- The consumption of anxiolytic treatments(During all the study)
- Duration of hospitalization(42 days)
- Clinical improvement on HDRS overall score(at day 7, 14, 28 and 42)
- Clinical improvement on BDI overall score(at day 7, 14, 28 and 42)
- Tolerance on dissociation(Day 1, 4, 7)
- Biomarkers(Day 1 and 14)
- Reduction of suicidal ideation(at day 0 and day 7)
- Clinical improvement on HDRS response rate(at day 7, 14, 28 and 42)
- Clinical improvement on HDRS remission rate(at day 7, 14, 28 and 42)
研究者
研究点 (4)
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