Clinical trial NCT02656342: 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?
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obsessive-Compulsive Disorder
Keywords: OCD
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: The Research Council of Norway
name: Helse Vest
First posted: 2016-01-14
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: All 15 OCD-teams in Norway refer patients to the study, thus providing nationwide coverage of relapsed or non-responsive OCD patients.

Through the Norwegian National OCD-implementation project all OCD-patients in Norway are ensured access to evidence based treatment. Standardized procedures for collection and storage of data (quality databases) are also established. These data will serve as reference data for standard treatment response, as well as provide detailed information regarding the first treatment-course for the relapsed OCD-patients.

The inclusion procedure implies that all relevant patients in Norway in the given time period will be offered participation. If this population turns out to be fewer than 160 patients during the study period, the inclusion period might be extended six months. If less than 160 patients are included at that point, analyses will be performed on the number of patients included by the end of the study period.

Inclusion Criteria:

* Outpatients
* ≥ 18 years
* Fulfilling diagnostic criteria of OCD according to the DSM-5
* Previously have received ERP-treatment delivered by trained therapist and either have responded and relapsed, or not responded to the treatment.
* Response is defined by ≥35% reduction with a post-treatment Y-BOCS score of ≤15, followed by a relapse as defined by \> 35% increase in Y-BOCS score from post-treatment, a Y-BOCS score of 16 or more, and a Clinical Global Impression-Improvement Scale (CGI-I) score of 6 ("much worse") or higher.
* Non-responders are defined as those with a reduction in Y-BOCS scores from pre- to post-of less than 35%, and with a Y-BOCS score of ≥16 after treatment. In order to be classified as non-responder as opposed to "drop-out" the patient has to previously have received a minimum of 6 sessions.
* There must be a minimum of 4 weeks since treatment ended.
* Fluent in Norwegian
* Signed informed consent

Exclusion Criteria related to the ERP:

* OCD symptoms primarily associated with hoarding
* Ongoing substance abuse/dependence
* Bipolar disorder or psychosis
* Ongoing suicidal ideation
* Mental Retardation, based on previous medical history
* If using antidepressants:
* Not on stable dosage 12 weeks before the intervention
* Unwilling to remain on stable dosage during the four intervention days
* Unwilling to refrain from anxiolytics (e.g. benzodiazepines) and alcohol during the two days of exposure.
* Living \> 1 hour drive by car/ train from the treatment location.

Exclusion Criteria related to the DCS:

* Pregnancy or breast feeding (the participants are informed that they will have to use contraception the two days when the DCS/placebo is administered. Females will be asked if they are pregnant, and in case of doubt a pregnancy test is provided)
* Renal impairment
* Hypersensitivity to D-Cycloserine
* Porphyria
* Epilepsy

Primary outcomes:
measure: Changes in Y-BOCS
timeFrame: 3 and 12 months, 5 years
measure: Changes in diagnostic status
timeFrame: 3 and 12 months, 5 years
measure: Changes in Y-BOCS evaluated by Jacobson and Truax, Reliable Change Index (RCI)
timeFrame: 3 and 12 months, 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Brumunddal
country: Norway
facility: Innlandet Hospital
city: Forde
country: Norway
facility: Forde Hospital
city: Kristiansand
country: Norway
facility: Sørlandet Hospital
city: Levanger
country: Norway
facility: Nord Trøndelag Hospital
city: Lorenskog
country: Norway
facility: Akershus University Hospital
city: Molde
country: Norway
facility: More and Romsdal Hospital
city: Moss
country: Norway
facility: Østfold Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Sandvika
country: Norway
facility: Vestre Viken
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tonsberg
country: Norway
facility: Sykehuset i Vestfold
city: Tromso
country: Norway
facility: Tromso University Hospital
city: Trondheim
country: Norway
facility: St. Olavs Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Gerd Kvale
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Bjarne Hansen
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Michelle Craske, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Jonathan Abramowitz, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Hime A Joeseph, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Martin D Franklin, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Michael Davis, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Lars-Göran Öst, PhD
role: STUDY_CHAIR
affiliation: Haukeland University Hospital
name: Odile van den Heuvel, PhD
role: STUDY_CHAIR
References:
citation: Kvale G, Hansen B, Hagen K, Abramowitz JS, Bortveit T, Craske MG, Franklin ME, Haseth S, Himle JA, Hystad S, Kristensen UB, Launes G, Lund A, Solem S, Ost LG. Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2020 Aug 3;3(8):e2013249. doi: 10.1001/jamanetworkopen.2020.13249.