Translational Approach to the Understanding and Treatment of Obsessive-Compulsive Disorder (OCD). Can D-Cycloserine Enhance and Stabilize the Treatment-response in Relapsed and Non-responding OCD-patients?
|ClinicalTrials.gov Identifier: NCT02656342|
Recruitment Status : Active, not recruiting
First Posted : January 14, 2016
Last Update Posted : March 5, 2019
In this randomized controlled trial (RCT) the investigators experimentally test if patients with Obsessive-Compulsive Disorder (OCD) who have received treatment with exposure and response prevention (ERP), but either relapsed or not responded, profit from the combination of concentrated exposure based treatment (cET) and the NMDA-agonist (N-methyl-d-aspartate) d-cycloserine (DCS), targeting fear relevant areas in amygdala and pre-frontal cortex.
The project expects to demonstrate a significant improvement in all groups, and anticipate that a higher proportion of the patients who receive DCS will show a better long-term gain from the treatment, as compared to the placebo group at follow-up (3 mon, 12 mon, and 5 years after treatment). In addition, the project will highlight changes in depression, sleep, global functioning, quality of life, work and social status. Changes in medication and use of health care will be included and related to the main objective of the study.
|Condition or disease||Intervention/treatment||Phase|
|Obsessive-Compulsive Disorder||Drug: D-Cycloserine Drug: Placebo||Phase 4|
A total of 160 relapsed and non-responding OCD-patients, treated with exposure and response prevention (ERP) in the specialist Health care in Norway, are planned to participate in the study: "Translation approach to the understanding and treatment of Obsessive-Compulsive Disorder (OCD). Can D-cycloserine (DCS) enhance and stabilize the treatment-response in relapsed and non-responding OCD-patients? A randomized, double-blind, placebo-controlled national study." Estimated start of inclusion is November 2015 and the inclusion period lasts for maximum 2 years. All participants are referred to the specialist health care and are pre-screen by the local OCD-team. Before inclusion, the patients will fill in a number of questionnaires on-line and all patients who meet the inclusion criteria will be invited to participate. Before the patient signs the informed consent form the patients will receive written and oral information about the study as well as watch a video describing the trial and what participation will imply. Before the 4-day concentrated exposure based treatment (cET) starts, the patients will undergo a clinical assessment interview by the local OCD-team, and will watch another video describing the trial in detail. They will also be assessed by SCID-I (Structured Clinical Interview) for DSM 5 as well as Y-BOCS (Yale-Brown Obsessive Compulsive Scale) interview by independent and specially trained psychologists. The cET is delivered in an "individual group format" which implies that the patient: therapist-ratio is 1:1, and that the treatment is delivered in groups of minimum 3 and maximum 6 patients. All groups are led by a specially trained cET therapist, and the local therapists are experienced OCD-therapists who are familiar with the cET format. Day 1 of the treatment (3 h) consists of psychoeducation and planning of exposure tasks. Day 2 and day 3 (both 8 h + contact in the evening) consist of individually tailored and therapist assisted exposure with a number of relevant triggers in a diversity of settings. All exposures are based on the LEaning in Technique (LET), where the patients are trained to recognize when the urge to ritualize starts, and to actively approach the trigger by "leaning into the anxiety". The exposures are also designed to optimize learned inhibition. In addition to individual exposure training, the group meets three times throughout the day. Day 2 and Day 3 the patient will take study medication before the exposures start. The study medication is D-Cycloserine (DCS) 250 mg, DCS 100 mg or placebo. In the afternoon Day 3, the patients' relatives/ friends are invited to a 2 h lecture/ psychoeducation on OCD and the current treatment. Day 4 the focus is on "lessons learnt" as well as on planning / specifying exposure tasks for the coming three weeks. Before and during the cET the patient will record data electronically via CheckWare (an electronic case report form database). The patient will continue registration of obsessions and compulsions through 3 weeks post cET. One week after cET a post-assessment with Y-BOCS will be performed by the independent assessor. After 3 months, the patient is invited to an individual visit at the clinic. 1 year and 5 years post treatment, the assessment team will perform follow-up telephone interviews.
Measures of anxiety, depression, global functioning, severity of the disorder, self-reported OCD-symptoms, sleep, quality of life, changes in work and social status as well as changes in medication and use of health care will be included and employed as secondary outcomes.
A total of 14 expert therapists have been trained to deliver cET to OCD-patients all over Norway. Patients, therapists and assessors are all blinded to the randomization. Interventions are recorded and rated for compliance and competence . All SCID-I and Y-BOCS assessments are recorded and standard procedures for rescoring are followed. All assessors are independent and specially trained.
A Scientific Advisory Board is established, also including representatives from the Norwegian OCD-association. The formal project partners are Haukeland University Hospital; Oslo University Hospital; St Olavs Hospital; Soerlandet Hospital and Moere and Romsdal Hospital.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Factorial Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Translational Approach to the Understanding and Treatment of Obsessive-Compulsive Disorder (OCD). Can D-Cycloserine Enhance and Stabilize the Treatment-response in Relapsed and Non-responding OCD-patients? A Randomized, Double-blind, Placebo-controlled National Study|
|Study Start Date :||November 2015|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2023|
Experimental: 250 mg DCS
64 patients receive 250 mg D-Cycloserine two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)
Predicted to enhance stabilization of the effects of concentrated exposure treatment
Experimental: 100 mg D-Cycloserine
64 patients receive 100 mg D-Cycloserine two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)
Predicted to enhance stabilization of the effects of concentrated exposure treatment
Active Comparator: Placebo
32 patients receive placebo two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)
Predicted to have no enhancing effect
Other Name: Sugar Pill
- Changes in Y-BOCS [ Time Frame: 3 and 12 months, 5 years ]Response is a ≥35% reduction of the individual patient's pre-treatment YBOCS score. A patient is remitted if the response criterion is fulfilled and the post-treatment Y-BOCS score is ≤12
- Changes in diagnostic status [ Time Frame: 3 and 12 months, 5 years ]Changes in Diagnostic status (DSM-5) assessed by SCID-I for DSM-5 at above specified points.
- Changes in Y-BOCS evaluated by Jacobson and Truax, Reliable Change Index (RCI) [ Time Frame: 3 and 12 months, 5 years ]The criteria of Jacobson and Truax: A.Change from pre- to post-assessment is statistically reliable at the 5%-level. (RCI). B. The patient's post-treatment score is within the distribution of the normal population defined as M+2Standard Deviation (SD), or outside the distribution of the patient population defined as M-2SD. Non-responder is not fulfilling the RCI. Partial responder fulfills the RCI but not the cut-off score Full responder fulfils the RCI and the cut-off score.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02656342
|Haukeland University Hospital|
|Bergen, Norway, 5021|
|Brumunddal, Norway, 2380|
|Forde, Norway, 6812|
|Kristiansand, Norway, 4604|
|Nord Trøndelag Hospital|
|Levanger, Norway, 7601|
|Akershus University Hospital|
|Lorenskog, Norway, 1478|
|More and Romsdal Hospital|
|Moss, Norway, 1635|
|Oslo University Hospital|
|Oslo, Norway, 0424|
|Sandvika, Norway, 1300|
|Stavanger University Hospital|
|Sykehuset i Vestfold|
|Tonsberg, Norway, 3103|
|Tromso University Hospital|
|St. Olavs Hospital|
|Trondheim, Norway, 7006|
|Principal Investigator:||Gerd Kvale||Haukeland University Hospital|
|Principal Investigator:||Bjarne Hansen||Haukeland University Hospital|
|Study Chair:||Michelle Craske, PhD||Haukeland University Hospital|
|Study Chair:||Jonathan Abramowitz, PhD||Haukeland University Hospital|
|Study Chair:||Hime A Joeseph, PhD||Haukeland University Hospital|
|Study Chair:||Martin D Franklin, PhD||Haukeland University Hospital|
|Study Chair:||Michael Davis, PhD||Haukeland University Hospital|
|Study Chair:||Lars-Göran Öst, PhD||Haukeland University Hospital|
|Study Chair:||Odile van den Heuvel, PhD||Haukeland University Hospital|