Clinical trial NCT06318806: Towards Remission and Full Recovery From Obsessive-compulsive Disorder
Official title: Towards Remission and Full Recovery From Obsessive-compulsive Disorder: Investigating the Efficacy of Inference-Based Cognitive-Behavioral Therapy When Standard Treatment Has Failed
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: Obsessive-Compulsive Disorder,
Treatment outcome
Predictors of Outcome
Exposure and Response Prevention
Inference-based Cognitive Behavioral Therapy
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2024-03-19
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a single site parallel-group randomized-controlled trial with an active run-in treatment. In the first phase of the trial, participants diagnosed with OCD will receive an active run-in treatment consisting of 18 sessions of ERP. In the second phase, non-remitters will be randomly allocated to another 18 sessions of I-CBT or continued treatment with ERP. Non-remission is operationalized in accordance with validated cut-off points established through international consensus and empirical findings (a score of \>12 on the YBOCS and a CGI-S rating of 3 or higher (mild to extremely ill) after the run-in treatment with ERP). I-CBT and continued ERP will be followed by a 6-month and 12-month follow-up conforming to current thinking on relapse and recovery in OCD. Treatments will be administered by trained therapists on a weekly one-on-one basis via videoconferencing for the duration of one hour.
Primary purpose: TREATMENT

Brief summary: Obsessive-compulsive disorder (OCD) is a disabling psychiatric illness that is characterized by distressing obsessional thoughts and time-consuming compulsive rituals. Exposure and Response Prevention (ERP) is a first-line psychological treatment of choice that requires patients to face their fears by being exposed to feared stimuli. This treatment has been shown to reduce symptoms in a significant proportion of patients. However, it is considered a difficult treatment and only a minority reach remission. Residual symptoms typically remain, or reappear after treatment, which is a risk for relapse. Inference-based Cognitive Behavioral Therapy (I-CBT) is a promising evidence-based treatment developed to overcome these limitations. I-CBT has already been found to be as effective as ERP and significantly more acceptable and easier to adhere to. There is also evidence that I-CBT is more effective for subgroups of patients. Consequently, the current research project is focused on improving treatments outcomes for those provide those who have previously unable to reach remission of their symptoms with ERP. Following an initial treatment with ERP, those that have been unable to reach remission, will be randomized to either I-CBT or more ERP. It is expected that I-CBT will be significantly more effective than providing patients with more of the same. In addition, the study aims to predict treatment outcome in order to be able to tell in advance which patients do not respond to ERP. The project is designed to maximize beneficial health outcomes with a stepped-care approach to treatment, but also to work towards a more personalized choice by being able to match patients in advance with the treatment that works best for them

Detailed description: Exposure and Response Prevention (ERP) improves symptoms in a significant proportion of patients, but only a minority reach remission after completing ERP (\~40%). Also, ERP is a difficult treatment that requires requires deliberate and prolonged exposure to fearful stimuli and is associated with lower levels of acceptability and tolerability. The current trial aims to overcome these limitations with Inference-Based Cognitive-Behavioral therapy (I-CBT) - a specialized form of Cognitive Behavioral Therapy that does not require provoking anxiety through exposure to fearful stimuli. To meet our objective, the current study consists of a randomized controlled trial preceded by a run-in treatment with ERP with a total of 160 patients diagnosed with OCD. Those that fail to reach remission with the run-in treatment (est. 60%) will be randomly allocated to either 18 sessions of ICBT or continued treatment with ERP. Patients will be diagnosed by standardized semi-structured interviews and treatment outcome will be assessed by gold standard clinician rated measurement of severity of symptoms by independent evaluators. For the first hypothesis, it is predicted that I-CBT is superior to continued ERP among those who have previously failed to reach remission with ERP in terms of: (a) greater improvement on our principal continuous outcome measure of OCD severity at post-treatment and follow-up; (b) clinical status at post-treatment and follow-up (treatment response, remission and relapse). For our second hypothesis, it is predicted that I-CBT is more acceptable and tolerable as compared to continued treatment with ERP for those previously unable to benefit sufficiently from ERP. For our third hypothesis, it is predicted that I-CBT is associated with more improvement on our secondary measures of outcome, including a) OC symptom dimensions and negative mood states, b) obsessive beliefs and reasoning processes, and c) psychosocial functioning. For our fourth hypothesis, it is predicted that ERP is associated with a higher frequency of combined treatment refusal and drop-out rates as compared to I-CBT. For our fifth hypothesis, tit is predicted that treatment outcome during ERP and I-CBT is associated with improvements in inferential confusion and feared-self perceptions. The secondary objective of the current proposal is to identify predictors of outcome and to use supervised machine learning to forecast which patients fail to reach remission following initial ERP treatment in order to enable the selection of patients to administer I-CBT as a first-line treatment in the future. Predictors will consist of previously identified risk factors of negative outcome, as well as proposed candidates in the extant literature

Eligibility criteria: Inclusion criteria:

1. a primary diagnosis of OCD according to DSM-5 criteria.
2. a score ≥ 18 on the Y-BOCS
3. age ≥ 18.
4. no change in medication during the 8 weeks before treatment for antidepressants (4 weeks for anxiolytics).
5. willingness to keep medication stable while participating in the study.
6. not undergoing a concurrent psychological treatment.
7. access to a computer or phone with internet access.

   Exclusion criteria:
8. evidence of a high level of suicidal ideation, suicidal intent or previous suicide attempts.
9. past or present psychotic or bipolar disorder.
10. neurocognitive disorder, pervasive developmental disorder or intellectual disability of a severity judged to significantly interfere with treatment and/or requiring treatment first.
11. substance abuse disorder of a severity judged to significantly interfere with treatment and/or requiring treatment first.

Primary outcomes:
measure: Yale-Brown Obsessive-Compulsive Scale -2 (Y-BOCS-2)
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
measure: Clinical Global Impression Scale (CGI)
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
Secondary outcomes:
measure: Vancouver Obsessional Compulsive Inventory (VOCI)
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
measure: Beck Depression Inventory (BDI)
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
measure: Inferential Confusion Questionnaire (ICQ)
timeFrame: After baseline before treatment, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatmen
measure: Dysfunctional Reasoning Processes Task (DRPT)
timeFrame: After baseline before treatment, change after 18 weeks of treatment, change in phase 2 after 18 weeks of treatment
measure: Fear of Self Questionnaire-Multidimensional Version
timeFrame: After baseline before treatment, change after 18 weeks of treatment, change in phase 2 after 18 weeks of treatment
measure: Obsessive Beliefs Questionnaire (OBQ-20)
timeFrame: After baseline before treatment, change after 18 weeks of treatment, change in phase 2 after 18 weeks of treatment
measure: Brunnsviken Brief Quality of Life Scale (BBQ)
timeFrame: After baseline before treatment, change after 18 weeks of treatment, change in phase 2 after 18 weeks of treatment
measure: Sheehan Disability Scale
timeFrame: Baseline, change after 9 weeks of treatment, 18 weeks of treatment, change in phase 2 after 9 weeks of treatment, change in phase 2 after 18 weeks of treatment, change after 6-month follow-up, change after 12-month follow-up
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Institut universitaire en santé mentale de Montréal
state: Quebec
Study officials:
affiliation: Institut universitaire en santé mentale de Montréal
name: Frederick Aardema, PhD
role: PRINCIPAL_INVESTIGATOR
References: