Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Completion Rate for Randomised Treatment Phase
研究概览
简要总结
Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam for depression relapse prevention in persons at high risk. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
详细描述
Participants will be recruited at admission to St Patrick's University Hospital for treatment of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-diagnosed recurrent unipolar depression and followed-up weekly to assess recovery according to standard criteria. Blood samples for epigenetic studies will be taken at baseline. Treatment-as-usual will continue throughout the entire trial. Participants who meet standardised response criteria will then be invited to be randomised to course of four two-weekly ketamine or midazolam (active comparator) infusions. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. Blood samples will be taken at four time-points in the first infusion session and before the final infusion for neuroplasticity biomarker studies.Trial Interventions: participants will receive four two-weekly infusions of either ketamine at 0.05mg/kg or midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Repeated infusions of ketamine have been shown to be safe and well-tolerated by patients with mental illness. Minor haemodynamic changes and psychotomimetic side-effects can occur and will be assessed regularly during infusions and for 200 minutes afterwards.
Participants will be followed up over six months to assess for relapse according to standardised criteria. This is the highest-risk period for relapse and investigators hypothesize that ketamine will provide additional neurotrophic support (assessed by the laboratory biomarker project) which will result in lower relapse rates when compared to midazolam.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Masking took place by sealed envelope random allocation and double blinding of participants and raters was assessed throughout. The anaesthesiologist administering infusions was aware of the allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old
- •Hamilton Rating Scale for Depression, 24-item (HRSD-24) score of ≥21
- •Voluntary admission for treatment of acute depressive episode
- •Meet DSM-IV criteria for recurrent depressive disorder (RDD): ≥2 previous depressive episodes with at least 2-months(consecutive) subthreshold or no symptoms in between PLUS(to enrich the sample for those at high risk for relapse) must also have experienced ≥3 major depressive episodes(including index episode) within the previous 2 years
- •For the randomised pilot trial, RDD patients must have:
- •received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
- •≥60% decrease from baseline HRSD-24 score and score ≤16
- •Standardised Mini-Mental State Examination (sMMSE) score of ≥24
- •able to provide informed consent
排除标准
- •Current involuntary admission
- •Medical condition rendering unfit for ketamine/midazolam
- •Active suicidal intention
- •History of Axis 1 diagnosis other than RDD
- •Electroconvulsive therapy (ECT) for treatment of current depressive episode
- •Alcohol/substance abuse in previous six months
- •Pregnancy or inability to confirm use of adequate contraception during the trial
研究组 & 干预措施
Ketamine
Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
干预措施: Ketamine (Drug)
Midazolam
Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
干预措施: Midazolam (Drug)
结局指标
主要结局
Completion Rate for Randomised Treatment Phase
时间窗: 2 years
The outcomes for this pilot trial are process outcomes, primarily rates of recruitment and retention. Thus, the completion rate for the randomised treatment phase is the primary outcome. The study is not designed to assess efficacy.
次要结局
- Depression Relapse Rate During Treatment and Follow-up Phase(8 months)
研究者
Prof Declan McLoughlin
Professor
St Patrick's Hospital, Ireland