Evaluation of Schemes of Administration of Intravenous Ketamine in Treatment-resistant Depression: Clinical-neuroimaging Correlation
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Depression Severity Hamilton Depression Rating Scale
研究概览
简要总结
Mexico, prevalence reported for major depressive disorder (MDD) is of 7.2%. It is currently in the top 5 causes of disability worldwide. One third of patients will not achieve remission after two treatments, being classified as treatment-resistant. In a neurochemical level, evidence shows dysregulation of the excitatory neurotransmitter Glutamate in patients with MDD. Chronic stress has been related to this dysregulation. Ketamine, has shown to regulate glutamatergic neurotransmission, and specially promote the release and production of neurotrophic factors key in the causes of MDD inhibited by glutamate dysregulation), and allow restoration of areas affected.
Clinical studies of ketamine in MDD have shown robust, durable , and rapid effects (during the first 4-24 hours), allowing a great opportunity for patients who do not achieve benefits from antidepressants or patients with suicidal ideation . These results have been reported in metaanalysis.
To our knowledge, there are no studies using Magnetic Resonance Spectroscopy, in areas related to MDD, after a series of ketamine administrations, which we think may show changes after this chronic administration and explain its antidepressant properties.
Goals: Provide clinical evidence of responseas well as a neurological basis or biomarker of response to a series of ketamine infusions.
详细描述
- Background 1.1 Major depressive disorder (MDD) MDD is a clinical syndrome characterized by the presence of low modo, anhedonia, appetite and weight changes, sleep disturbances, psychomotor alterations, fatigue, guilt and low self-esteem, ideas related to death or suicide, and concentration difficulties.
MDD represents one of the first causes of disability worldwide. In Mexico, prevalence is estimated in 7.2% of the population. In accordance to the largest clinical trial of MDD, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression), up to one third of the patients will not achieve remission after 4 treatment strategies. These obligates research of new treatments for MDD and treatment-resistant depression TRD.
1.2 Treatment-resistant Depression (TRD) There is a lack of consensus to define TRD, with multiple criteria used by distinct authors. However, the most used definition is the failure to achieve response or remission after two consecutive treatments at an adequate dose and duration, considering the last episode.
1.3 Physiopathology of MDD. Historically, serotonin and noradrenaline disturbances in production, metabolism and reuptake have been implicated in MDD, as well as dopamine. However, this hypothesis seems insufficient in explaining the lack of immediate response, and the lack of response of up to one third of patients.
It is necessary to understand MDD as a multifactorial disorder (biological, psychological, and environmental agents). At a genetic level, some polymorphisms have been related to the appearance of MDD, such as the gen associated with the glucocorticoid receptor NR3C1, the one related to the monoaminooxidase-A, and the one related to the glucogen kinase-synthase 3. Heredability for MDD has been calculated around 37%.
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)
盲法说明
Double-blind
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
- •Age: 18-65 years
- •MDD diagnosis as provided by DSM-5 criteria
- •TRD as defined by failure to achieve response to two consecutive antidepressant therapies at an adequate dose and duration
- •Patients approving inclusion by signing the informed consent
排除标准
- •Comorbidity with other mental and neurological disorders (except generalized anxiety disorder)
- •Substance use disorders at least 3 months prior to enrollment
- •Evidence of structural abnormalities in basal MRI
- •Pregnancy or lactation
- •Hypersensitivity to ketamine
- •Cardiac failure
- •Personal history of psychosis
- •First-degree relatives with history of psychosis
- •Uncontrolled close-angle glaucoma
- •Neurological disease (present)
- •Uncontrolled Hypertension
- •Contraindications for the realization of H1-MRS.
研究组 & 干预措施
Ketamine
Ketamine 50 MG/ML - at a dose of 0.5 mg/kg IV diluted in 100cc of saline solution 0.9% over 40 minutes.
The intervention will be done twice weekly for 8 weeks.
干预措施: Ketamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV (Drug)
Placebo
Saline solution 0.9% over 40 minutes. The intervention will be done twice weekly for 2 weeks, and then patients will receive intervention with ketamine as described above in the Active Comparator.
干预措施: Ketamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV (Drug)
结局指标
主要结局
Depression Severity Hamilton Depression Rating Scale
时间窗: 4, 24, 72 hours, weekly up to 12 weeks or until relapse (Change from baseline to each measure)
Depression Severity (10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe). Higher values represent a worse severity, but not necessarily outcome.
Glutamate
时间窗: Basal, 10 minutes during intervention, 24 hours after, 4 weeks after (Change from baseline to each measure)
Glutamate levels in the pgACC basal and after the last intervention with ketamine or placebo
GABA
时间窗: Basal, 10 minutes during intervention, 24 hours after, 4 weeks after (Change from baseline to each measure)
GABA levels in the pgACC basal and after the last intervention with ketamine or placebo
Depression Severity Montgomery-Asberg Depression Rating Scale)
时间窗: 4, 24, 72 hours, weekly up to 12 weeks or until relapse (Change from baseline to each measure). Higher values represent a worse severity, but not necessarily outcome.
Depression Severity (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe)
次要结局
未报告次要终点
研究者
Rodrigo Pérez Esparza
Medical Sciences Investigator
National Institute of Neurology and Neurosurgery, Mexico