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?

NCT ID: NCT02656342

Last Updated: 2021-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-02-28

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.

Conditions

Obsessive-Compulsive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

250 mg DCS

64 patients receive 250 mg D-Cycloserine two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)

Group Type: EXPERIMENTAL

D-Cycloserine

Intervention Type: DRUG

Predicted to enhance stabilization of the effects of concentrated exposure treatment

100 mg D-Cycloserine

64 patients receive 100 mg D-Cycloserine two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)

Group Type: EXPERIMENTAL

D-Cycloserine

Intervention Type: DRUG

Predicted to enhance stabilization of the effects of concentrated exposure treatment

Placebo

32 patients receive placebo two consecutive days in combination with therapist assisted concentrated exposure therapy (cET)

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Predicted to have no enhancing effect

Interventions

D-Cycloserine

Predicted to enhance stabilization of the effects of concentrated exposure treatment

Intervention Type: DRUG

Placebo

Predicted to have no enhancing effect

Intervention Type: DRUG

Other Intervention Names

DCS; Cycloserine; Sugar Pill

Eligibility Criteria

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

• 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.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Research Council of Norway

OTHER

Sponsor Role: collaborator

Helse Vest

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerd Kvale

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Bjarne Hansen

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Michelle Craske, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Jonathan Abramowitz, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Hime A Joeseph, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Martin D Franklin, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Michael Davis, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Lars-Göran Öst, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Odile van den Heuvel, PhD

Role: STUDY_CHAIR

Haukeland University Hospital

Locations

Haukeland University Hospital

Bergen, , Norway

Innlandet Hospital

Brumunddal, , Norway

Forde Hospital

Førde, , Norway

Sørlandet Hospital

Kristiansand, , Norway

Nord Trøndelag Hospital

Levanger, , Norway

Akershus University Hospital

Lorenskog, , Norway

More and Romsdal Hospital

Molde, , Norway

Østfold Hospital

Moss, , Norway

Oslo University Hospital

Oslo, , Norway

Vestre Viken

Sandvika, , Norway

Stavanger University Hospital

Stavanger, , Norway

Tromso University Hospital

Tromsø, , Norway

St. Olavs Hospital

Trondheim, , Norway

Sykehuset i Vestfold

Tønsberg, , Norway

Countries

Norway

References

Berg H, Tjelle K, Hansen B, Solem S, Bjorgvinsson T, Kvale G, Hagen K. Treatment expectancy and credibility as predictors of concentrated exposure treatment outcomes in patients with difficult-to-treat obsessive-compulsive disorder. BMC Psychiatry. 2025 Mar 25;25(1):275. doi: 10.1186/s12888-025-06737-z.

Reference Type: DERIVED

PMID: 40133857 (View on PubMed)

Tjelle K, Opstad HB, Solem S, Kvale G, Wheaton MG, Bjorgvinsson T, Hansen B, Hagen K. Patient adherence as a predictor of acute and long-term outcomes in concentrated exposure treatment for difficult-to-treat obsessive-compulsive disorder. BMC Psychiatry. 2024 Apr 30;24(1):327. doi: 10.1186/s12888-024-05780-6.

Reference Type: DERIVED

PMID: 38689256 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32789516 (View on PubMed)

Related Links

http://www.helse-bergen.no/ocd

Homepage for the OCD-team i nBergen and the national OCD-study

Other Identifiers

2013-002574-49

Identifier Type: -

Identifier Source: org_study_id