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?

NCT02656342 | Completed Phase 4

• 1 other identifier: 2013-002574-49
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 14

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.

Conditions

Obsessive-Compulsive Disorder

Keywords

OCD

Outcome Measures

Primary Outcomes (3)

• Changes in Y-BOCS

  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

  3 and 12 months, 5 years

• Changes in diagnostic status

  Changes in Diagnostic status (DSM-5) assessed by SCID-I for DSM-5 at above specified points.

  3 and 12 months, 5 years

• Changes in Y-BOCS evaluated by Jacobson and Truax, Reliable Change Index (RCI)

  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.

  3 and 12 months, 5 years

Study Arms (3)

250 mg DCS

EXPERIMENTAL

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

Drug: D-Cycloserine

100 mg D-Cycloserine

EXPERIMENTAL

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

Drug: D-Cycloserine

Placebo

ACTIVE COMPARATOR

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

Drug: Placebo

Interventions

D-Cycloserine DRUG

Predicted to enhance stabilization of the effects of concentrated exposure treatment

Also known as: DCS, Cycloserine

100 mg D-Cycloserine; 250 mg DCS

Placebo DRUG

Predicted to have no enhancing effect

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Haukeland University Hospital: lead
• The Research Council of Norway: collaborator
• Helse Vest: collaborator

Study Sites (14)

Haukeland University Hospital

Bergen, 5021, Norway

Location

Innlandet Hospital

Brumunddal, 2380, Norway

Location

Forde Hospital

Førde, 6812, Norway

Location

Sørlandet Hospital

Kristiansand, 4604, Norway

Location

Nord Trøndelag Hospital

Levanger, 7601, Norway

Location

Akershus University Hospital

Lorenskog, 1478, Norway

Location

More and Romsdal Hospital

Molde, Norway

Location

Østfold Hospital

Moss, 1635, Norway

Location

Oslo University Hospital

Oslo, 0424, Norway

Location

Vestre Viken

Sandvika, 1300, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

Tromso University Hospital

Tromsø, Norway

Location

St. Olavs Hospital

Trondheim, 7006, Norway

Location

Sykehuset i Vestfold

Tønsberg, 3103, Norway

Location

Related Publications (4)

• Tjelle K, Hansen B, Solem S, Wheaton MG, Kvale G, Hagen K. Concentrated ERP for Patients With Difficult-to-Treat OCD: Insight as a Predictor of Acute and Long-Term Outcomes. Depress Anxiety. 2025 Dec 11;2025:8960147. doi: 10.1155/da/8960147. eCollection 2025.

  PMID: 41425659 DERIVED

• 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.

  PMID: 40133857 DERIVED

• 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.

  PMID: 38689256 DERIVED

• 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.

  PMID: 32789516 DERIVED

Related Links

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

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Cycloserine; Sugars

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Carbohydrates

Study Officials

• Gerd Kvale

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

• Bjarne Hansen

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: January 14, 2016
• Study Start: November 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: February 1, 2019
• Last Updated: February 11, 2021

Record last verified: 2021-02

Locations

NO (14)