Alternative Treatment to Reduce Chronicity in OCD: Research Into Brain Response and Adequacy of Treatment A Randomized Controlled Non-inferiority Trial Into the Effectiveness and Working Mechanisms of IBA in Comparison to CBT.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 246
- 试验地点
- 14
- 主要终点
- Change from baseline score on the Yale Brown Obsessive Compulsive Scale (YBOCS) after 20 sessions IBA or CBT, and after 6 months and 1 year post treatment
研究概览
简要总结
Rationale: Obsessive-Compulsive Disorder (OCD) is a disabling neuropsychiatric disorder that often has a chronic disease course. The standard psychotherapeutic treatment Cognitive Behavioural Therapy (CBT) is unable to redeem about half of all patients and is rejected by many because of its anxiety provoking methods. A promising alternative is the Interference Based Approach (IBA), which appears to be as effective as CBT, and more effective for patients with poor insight. The current study will investigate the proposed IBA non-inferiority to CBT. Furthermore, the neurobiological working mechanisms of both treatments will be investigated. Both treatment modalities are expected to alter activity and connectivity in different functional brain networks. In order to lead the way towards personalized care for OCD patients, clinical and neurobiological predictors of response to treatment will be studied. The eventual aim of this study is to prevent the demoralizing effect of undergoing an ineffective treatment by future prediction of whether an individual patient will respond better to IBA or CBT. This also contributes to solving the costs and waiting times for CBT.
Objective: To investigate non-inferiority of IBA compared to CBT and to unravel the neurobiological working mechanisms of both treatment modalities.
Study design: Multicentre randomized controlled trial.
Study population: 203 adults with a primary diagnosis of OCD and 43 healthy controls, matched on gender, age and educational level.
Intervention: The 203 adults with the primary diagnosis of OCD will be divided into the experimental- (IBA) and control intervention (CBT). Healthy controls will not receive an intervention.
Main study parameters/endpoints: Clinical measures (e.g. severity of OCD symptoms, disease insight), neurocognitive capabilities (performance on neuropsychological tests), neural correlates on brain structure (i.e. white matter integrity, grey matter volume) and brain function (i.e., activation and connectivity during resting state and symptom provocation) using 3 Tesla magnetic resonance imaging.
详细描述
Sample size calculation: for the primary study objective, the 95-95 approach to determine the non-inferiority margin was used. Results of a meta-analysis on the effectiveness of CBT for OCD indicated that the mean (95 percent Confidence Interval (1.04) generates a non-inferiority margin of .42. Expressed in scores on the primary outcome measure Yale Brown Obsessive Compulsive Scale (YBOCS), this would be a loss of about 2 points on this scale with a range of 0-40, which is clinically almost negligible. Applying an alpha of 0.05, a beta of 80%, and a .42 non-inferiority margin, a sample size of 71 per arm is adequate. Since analyses have to be run on the per protocol (P)- and the intention-to-treat (ITT) sample, 203 participants have to be recruited (anticipating 30 percent drop-out). Moreover, this sample size allows testing the secondary hypothesis: IBA is more effective than CBT for patients with OCD with poor insight (approximately 25 percent of the population). Applying a two-sided alpha of 0.05 and a beta of 80 percent and effect size of Cohen's d =1, a sample of 34 participants is needed (in a previous study a between groups effect of 1.7 was found), anticipating 30 percent drop-out, 48 participants with poor insight at baseline are needed.
Previous studies into the influence of psychotherapy for OCD on brain structure and functioning have used sample sizes of 9-45. Based on their findings, analysing data for a minimum of 30 participants per condition is planned to explore the working mechanisms of the treatment modalities. Anticipating an upper limit of 30 percent drop-out rate, 2 x 43 respondents will be included, as well as 43 control subjects.
Adherence to treatment protocol: the therapists will be extensively trained in adherence to the protocol and the use of the premade forms for exercises and homework assignments. All treatment sessions will be audiotaped. Each therapist will receive supervision. During supervision, the supervisor will listen to parts of the audiotapes to give feedback and to make sure that the therapist does not drift from the protocol.
Furthermore, after the study is completed, there will be an adherence check. A trained blinded assessor will sample-wise listen to audiotapes of the session to score whether it was an IBA of CBT session.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: patients will be assessed during five time points, including two follow ups. Further, patients will fill in two questionnaires after each treatment session. Participants of the additional imaging part will be subjected to two extra sessions for MRI scanning and cognitive testing. Healthy controls will be measured once.
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
- Single (Investigator)
盲法说明
The research assessors will be blinded for treatment allocation. Partcipants and clinicians will be requested not to reveal information about treatment allocation to the assessors.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants
- •Referred to one of the participating sites for OCD treatment
- •Age 18 or above
- •Primary Diagnostic Statistical Manual (DSM)-5 diagnosis of OCD (established by the Structured Clinical Interview for DSM-5 (SCID)
- •Moderate to severe OCD symptoms (expressed as a minimum score of 16 on the Yale Brown Obsessive Compulsive Scale (YBOCS)
- •Not currently using psychotropic medication, or on a stable dose for at least 12 weeks prior to randomisation with no plans to change the dose during the course of the study (this will be monitored during the study)
- •If CBT already has been received for OCD, treatment has ended at least 26 weeks before study participation.
- •Age 18 or above
排除标准
- •Suffering from a current psychotic disorder, organic mental disorder, substance use disorder or mental retardation
- •No sufficient command of the Dutch language
- •Patients will be asked if they are willing to participate in the imaging study as well, including brain scans pre- and posttreatment. The selection will continue until 86 eligible participants are included for the MRI part of the study. Additional exclusion criteria apply for this sub study:
- •Use of psychotropic medication other than Selective Serotonin Reuptake Inhibitor/Selective Norepinephrine Reuptake Inhibitor/clomipramine (e.g. antipsychotics). Occasional (not daily, a maximal equivalent of 10 mg. diazepam at a time) use of benzodiazepines/sleeping medication is allowed, if the participant is willing to tolerate to refrain from use for at least a week before the MRI scanning session, and able to tolerate this period of refrainment.
- •Pregnancy
- •Iron in the body
- •Claustrophobia
- •Any known neurological diseases (including epilepsy) or brain surgery
- •Head trauma that resulted in unconsciousness for at least 1 hour
- •Age 65 or above
- •Age 65 or above
- •Current DSM-5 diagnosis (established by the SCID)
- •Personal history of DSM-5 diagnosis, except for depressive or anxiety disorder longer than 12 months ago
- •Personal history or current use of psychotropic medication (excluding sporadic use of sedatives/benzodiazepines, not having been used the week prior to participation
- •First-degree relative (parent/sibling/child) with OCD or tic-disorder
- •Insufficient command of the Dutch language
- •Pregnancy
- •Iron in the body
- •Claustrophobia
- •Any known neurological diseases (including epilepsy), or past brain surgery
- •Head trauma that resulted in unconsciousness for at least 1 hour
结局指标
主要结局
Change from baseline score on the Yale Brown Obsessive Compulsive Scale (YBOCS) after 20 sessions IBA or CBT, and after 6 months and 1 year post treatment
时间窗: at baseline; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20
The YBOCS (range 0-40, higher values representing worse outcome) measures OCD symptom severity
次要结局
- Change form baseline on the Yale-Brown Obsessive Compulsive Scale self-report questionnaire (YBOCS-SR) after each therapy session IBA or CBT(at baseline; at every therapy session at week 0-20)
- Change from baseline performance on Visual Spatial N-back Task after 20 sessions of IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline brain morphology measured by Magnetic Resonance Imaging (MRI) after 20 sessions IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline structural connectivity measured by Diffusion Tensor Imaging (DTI) after 20 sessions IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline activity and functional connectivity measured by resting state functional Magnetic Resonance Imaging (rs-fMRI) after 20 sessions IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline activity and functional connectivity measured by functional Magnetic Resonance Imaging (fMRI) during OCD symptom provocation after 20 sessions IBA or CBT(at baseline; post intervention at week 20)
- Treatment Acceptability/Adherence Scale (TAAS)(post intervention at week 20)
- Change from baseline performance on Tower of London Task (ToL) after 20 sessions of IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline score on the Beck Anxiety Inventory (BDI), after 10 sessions IBA or CBT, at post treatment after 20 sessions IBA or CBT and after 6 months and 1 year post treatment(at baseline;mid-treatment at week 10; post intervention at week 20;at follow up 6 months post week 20; at follow up 12 months post week 20)
- Change from baseline score on Euroquol, after 10 sessions IBA or CBT, at post treatment after 20 sessions IBA or CBT and after 6 months and 1 year post treatment(at baseline;mid-treatment at week 10; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20)
- Change from baseline score on the Overvalued Ideas Scale (OVIS) after 20 sessions IBA or CBT, and after 6 months and 1 year post treatment(at baseline; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20)
- Change from baseline on the Overvalued Ideas Scale - Self Report (OVIS-SR)(at baseline; at every therapy session at week 0-20)
- Change from baseline performance on Stop Signal Task (SST) after 20 sessions of IBA or CBT(at baseline; post intervention at week 20)
- Change from baseline score on the Beck Depression Inventory (BDI), after 10 sessions IBA or CBT, at post treatment after 20 sessions IBA or CBT and after 6 months and 1 year post treatment(at baseline;mid-treatment at week 10; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20)
- Change from baseline score on Sheehan disability Scale (SDS), after 10 sessions IBA or CBT, at post treatment after 20 sessions IBA or CBT and after 6 months and 1 year post treatment(at baseline;mid-treatment at week 10; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20)
- Change from baseline score on Relationship Satisfaction Scale (RSS), after 10 sessions IBA or CBT, at post treatment after 20 sessions IBA or CBT and after 6 months and 1 year post treatment(at baseline;mid-treatment at week 10; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20)