Alternative Treatment to Reduce Chronicity in OCD: Research Into Brain Response and Adequacy of Treatment

NCT03929081 | Completed

• 1 other identifier: NL66299.029.18
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 7

Brief Summary

Rationale: Obsessive-Compulsive Disorder (OCD) is a disabling neuropsychiatric disorder that often has a chronic disease course. The standard psychotherapeutic treatment Cognitive Behavioural Therapy (CBT) is unable to redeem about half of all patients and is rejected by many because of its anxiety provoking methods. A promising alternative is the Interference Based Approach (IBA), which appears to be as effective as CBT, and more effective for patients with poor insight. The current study will investigate the proposed IBA non-inferiority to CBT. Furthermore, the neurobiological working mechanisms of both treatments will be investigated. Both treatment modalities are expected to alter activity and connectivity in different functional brain networks. In order to lead the way towards personalized care for OCD patients, clinical and neurobiological predictors of response to treatment will be studied. The eventual aim of this study is to prevent the demoralizing effect of undergoing an ineffective treatment by future prediction of whether an individual patient will respond better to IBA or CBT. This also contributes to solving the costs and waiting times for CBT. Objective: To investigate non-inferiority of IBA compared to CBT and to unravel the neurobiological working mechanisms of both treatment modalities. Study design: Multicentre randomized controlled trial. Study population: 203 adults with a primary diagnosis of OCD and 43 healthy controls, matched on gender, age and educational level. Intervention: The 203 adults with the primary diagnosis of OCD will be divided into the experimental- (IBA) and control intervention (CBT). Healthy controls will not receive an intervention. Main study parameters/endpoints: Clinical measures (e.g. severity of OCD symptoms, disease insight), neurocognitive capabilities (performance on neuropsychological tests), neural correlates on brain structure (i.e. white matter integrity, grey matter volume) and brain function (i.e., activation and connectivity during resting state and symptom provocation) using 3 Tesla magnetic resonance imaging.

Conditions

Obsessive-Compulsive Disorder

Keywords

Obsessive-Compulsive Disorder; Inference Based Approach (IBA); Cognitive Behavioral Therapy (CBT); Personalized care; Neurocognitive working mechanisms of treatment; Non-inferiority; Prediction of treatment efficiency

Outcome Measures

Primary Outcomes (1)

• Change from baseline score on the Yale Brown Obsessive Compulsive Scale (YBOCS) after 20 sessions IBA or CBT, and after 6 months and 1 year post treatment

  The YBOCS (range 0-40, higher values representing worse outcome) measures OCD symptom severity

  at baseline; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20

Secondary Outcomes (18)

• Change from baseline brain morphology measured by Magnetic Resonance Imaging (MRI) after 20 sessions IBA or CBT

  at baseline; post intervention at week 20

• Change from baseline structural connectivity measured by Diffusion Tensor Imaging (DTI) after 20 sessions IBA or CBT

  at baseline; post intervention at week 20

• Change from baseline activity and functional connectivity measured by resting state functional Magnetic Resonance Imaging (rs-fMRI) after 20 sessions IBA or CBT

  at baseline; post intervention at week 20

• Change from baseline activity and functional connectivity measured by functional Magnetic Resonance Imaging (fMRI) during OCD symptom provocation after 20 sessions IBA or CBT

  at baseline; post intervention at week 20

• Change from baseline score on the Overvalued Ideas Scale (OVIS) after 20 sessions IBA or CBT, and after 6 months and 1 year post treatment

  at baseline; post intervention at week 20; at follow up 6 months post week 20; at follow up 12 months post week 20

Other Outcomes (2)

• Change on performance on the Confidence Accuracy Task after 20 sessions of IBA or CBT

  at baseline; post intervention at week 20

• Change of valence rating of symptom provocation stimuli after 20 sessions of IBA or CBT

  at baseline; post intervention at week 20

Study Arms (3)

Inference Based Approach (IBA)

EXPERIMENTAL

The IBA treatment, a focused form of psychotherapy consists of twenty 45-minutes sessions, delivered weekly. The IBA model is based on the assumption that patients with OCD feel the need to perform compulsive acts because they misjudge the actual state of affairs, for example fearing that an appliance is on when it is visibly off. It is assumed that certain reasoning processes lead to these erroneous conclusions and distract the patient's attention from observable reality. IBA teaches patients how to defend themselves against the absorbing and confusing effect of obsessive reasoning processes and how to stay in touch with reality by actively relying on the sensory information of the very moment. As a consequence, the patient realizes that any compulsive act is superfluous and feels able to omit it.

Behavioral: Inference Based Approach (IBA)

Cognitive Behavior Therapy (CBT)

ACTIVE COMPARATOR

In the control condition, the patients will receive twenty 45-minutes sessions of CBT consisting of self-guided exposure in vivo with response prevention (ERP) and cognitive therapy (CT), both standardized according to evidence-based session-by-session protocols, containing standardized forms for exercises and homework assignments.

Behavioral: Cognitive Behavioural Therapy (CBT)

No intervention (healthy controls)

NO INTERVENTION

The healthy control group will receive no intervention.

Interventions

Inference Based Approach (IBA) BEHAVIORAL

The Inference Based Approach aims at strengthening reality testing in patients with Obsessive-Compulsive Disorder, by teaching the patient to actively rely on sensory information.

Also known as: Psychotherapy

Inference Based Approach (IBA)

Cognitive Behavioural Therapy (CBT) BEHAVIORAL

CBT teaches the patient with Obsessive-Compulsive Disorder to refrain from compulsive acts.

Also known as: Psychotherapy

Cognitive Behavior Therapy (CBT)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants
• Referred to one of the participating sites for OCD treatment
• Age 18 or above
• Primary Diagnostic Statistical Manual (DSM)-5 diagnosis of OCD (established by the Structured Clinical Interview for DSM-5 (SCID)
• Moderate to severe OCD symptoms (expressed as a minimum score of 16 on the Yale Brown Obsessive Compulsive Scale (YBOCS)
• Not currently using psychotropic medication, or on a stable dose for at least 12 weeks prior to randomisation with no plans to change the dose during the course of the study (this will be monitored during the study)
• If CBT already has been received for OCD, treatment has ended at least 26 weeks before study participation.
• Controls
• \- Age 18 or above

You may not qualify if:

• Patients
• Suffering from a current psychotic disorder, organic mental disorder, substance use disorder or mental retardation
• No sufficient command of the Dutch language
• Use of psychotropic medication other than Selective Serotonin Reuptake Inhibitor/Selective Norepinephrine Reuptake Inhibitor/clomipramine (e.g. antipsychotics). Occasional (not daily, a maximal equivalent of 10 mg. diazepam at a time) use of benzodiazepines/sleeping medication is allowed, if the participant is willing to tolerate to refrain from use for at least a week before the MRI scanning session, and able to tolerate this period of refrainment.
• Pregnancy
• Iron in the body
• Claustrophobia
• Any known neurological diseases (including epilepsy) or brain surgery
• Head trauma that resulted in unconsciousness for at least 1 hour
• Age 65 or above
• Controls
• Age 65 or above
• Current DSM-5 diagnosis (established by the SCID)
• Personal history of DSM-5 diagnosis, except for depressive or anxiety disorder longer than 12 months ago
• Personal history or current use of psychotropic medication (excluding sporadic use of sedatives/benzodiazepines, not having been used the week prior to participation

Sponsors & Collaborators

• GGZ Centraal: lead
• Amsterdam UMC, location VUmc: collaborator
• GGZ inGeest: collaborator
• PsyQ: collaborator
• Radboud University Medical Center: collaborator

Study Sites (7)

GGz Drenthe

Assen, Drenthe, 9404 LA, Netherlands

Location

GGz Centraal

Ermelo, Gelderland, 3853 LC, Netherlands

Location

Pro Persona

Nijmegen, Gelderland, 6503 CG, Netherlands

Location

Mondriaan

Maastricht, Limburg, 6226 NB, Netherlands

Location

GGz InGeest

Amsterdam, North Holland, 1081 HJ, Netherlands

Location

Amsterdam UMC, VUmc

Amsterdam, North Holland, 1081 HV, Netherlands

Location

PsyQ Amsterdam

Amsterdam, North Holland, 1101 DM, Netherlands

Location

Related Publications (19)

• Abramowitz JS. The psychological treatment of obsessive-compulsive disorder. Can J Psychiatry. 2006 Jun;51(7):407-16. doi: 10.1177/070674370605100702.

  PMID: 16838822 BACKGROUND

• Abramowitz JS, Taylor S, McKay D. Potentials and limitations of cognitive treatments for obsessive-compulsive disorder. Cogn Behav Ther. 2005;34(3):140-7. doi: 10.1080/16506070510041202.

  PMID: 16195053 BACKGROUND

• Adler CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM. fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder. J Psychiatr Res. 2000 Jul-Oct;34(4-5):317-24. doi: 10.1016/s0022-3956(00)00022-4.

  PMID: 11104844 BACKGROUND

• Andrews-Hanna JR, Smallwood J, Spreng RN. The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Ann N Y Acad Sci. 2014 May;1316(1):29-52. doi: 10.1111/nyas.12360. Epub 2014 Feb 6.

  PMID: 24502540 BACKGROUND

• Banks SJ, Eddy KT, Angstadt M, Nathan PJ, Phan KL. Amygdala-frontal connectivity during emotion regulation. Soc Cogn Affect Neurosci. 2007 Dec;2(4):303-12. doi: 10.1093/scan/nsm029.

  PMID: 18985136 BACKGROUND

• Bari A, Robbins TW. Inhibition and impulsivity: behavioral and neural basis of response control. Prog Neurobiol. 2013 Sep;108:44-79. doi: 10.1016/j.pneurobio.2013.06.005. Epub 2013 Jul 13.

  PMID: 23856628 BACKGROUND

• Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, Benedetti F, Beucke JC, Bollettini I, Bose A, Brem S, Calvo A, Cheng Y, Cho KI, Dallaspezia S, Denys D, Fitzgerald KD, Fouche JP, Gimenez M, Gruner P, Hanna GL, Hibar DP, Hoexter MQ, Hu H, Huyser C, Ikari K, Jahanshad N, Kathmann N, Kaufmann C, Koch K, Kwon JS, Lazaro L, Liu Y, Lochner C, Marsh R, Martinez-Zalacain I, Mataix-Cols D, Menchon JM, Minuzzi L, Nakamae T, Nakao T, Narayanaswamy JC, Piras F, Piras F, Pittenger C, Reddy YC, Sato JR, Simpson HB, Soreni N, Soriano-Mas C, Spalletta G, Stevens MC, Szeszko PR, Tolin DF, Venkatasubramanian G, Walitza S, Wang Z, van Wingen GA, Xu J, Xu X, Yun JY, Zhao Q; ENIGMA OCD Working Group; Thompson PM, Stein DJ, van den Heuvel OA. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis. Am J Psychiatry. 2017 Jan 1;174(1):60-69. doi: 10.1176/appi.ajp.2016.16020201. Epub 2016 Sep 9.

  PMID: 27609241 BACKGROUND

• Eisen JL, Rasmussen SA, Phillips KA, Price LH, Davidson J, Lydiard RB, Ninan P, Piggott T. Insight and treatment outcome in obsessive-compulsive disorder. Compr Psychiatry. 2001 Nov-Dec;42(6):494-7. doi: 10.1053/comp.2001.27898.

  PMID: 11704942 BACKGROUND

• O'Connor KP, Aardema F, Bouthillier D, Fournier S, Guay S, Robillard S, Pelissier MC, Landry P, Todorov C, Tremblay M, Pitre D. Evaluation of an inference-based approach to treating obsessive-compulsive disorder. Cogn Behav Ther. 2005;34(3):148-63. doi: 10.1080/16506070510041211.

  PMID: 16195054 BACKGROUND

• van Oppen P, van Balkom AJ, de Haan E, van Dyck R. Cognitive therapy and exposure in vivo alone and in combination with fluvoxamine in obsessive-compulsive disorder: a 5-year follow-up. J Clin Psychiatry. 2005 Nov;66(11):1415-22. doi: 10.4088/jcp.v66n1111.

  PMID: 16420079 BACKGROUND

• Visser HA, van Oppen P, van Megen HJ, Eikelenboom M, van Balkom AJ. Obsessive-compulsive disorder; chronic versus non-chronic symptoms. J Affect Disord. 2014 Jan;152-154:169-74. doi: 10.1016/j.jad.2013.09.004. Epub 2013 Sep 13.

  PMID: 24084621 BACKGROUND

• Schumi J, Wittes JT. Through the looking glass: understanding non-inferiority. Trials. 2011 May 3;12:106. doi: 10.1186/1745-6215-12-106.

  PMID: 21539749 BACKGROUND

• Olatunji BO, Davis ML, Powers MB, Smits JA. Cognitive-behavioral therapy for obsessive-compulsive disorder: a meta-analysis of treatment outcome and moderators. J Psychiatr Res. 2013 Jan;47(1):33-41. doi: 10.1016/j.jpsychires.2012.08.020. Epub 2012 Sep 20.

  PMID: 22999486 BACKGROUND

• Visser HA, van Megen H, van Oppen P, Eikelenboom M, Hoogendorn AW, Kaarsemaker M, van Balkom AJ. Inference-Based Approach versus Cognitive Behavioral Therapy in the Treatment of Obsessive-Compulsive Disorder with Poor Insight: A 24-Session Randomized Controlled Trial. Psychother Psychosom. 2015;84(5):284-93. doi: 10.1159/000382131. Epub 2015 Aug 6.

  PMID: 26278470 BACKGROUND

• Thorsen AL, van den Heuvel OA, Hansen B, Kvale G. Neuroimaging of psychotherapy for obsessive-compulsive disorder: A systematic review. Psychiatry Res. 2015 Sep 30;233(3):306-13. doi: 10.1016/j.pscychresns.2015.05.004. Epub 2015 May 16.

  PMID: 26228566 BACKGROUND

• Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989 Nov;46(11):1006-11. doi: 10.1001/archpsyc.1989.01810110048007.

  PMID: 2684084 BACKGROUND

• Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989 Nov;46(11):1012-6. doi: 10.1001/archpsyc.1989.01810110054008.

  PMID: 2510699 BACKGROUND

• Rubinov M, Sporns O. Complex network measures of brain connectivity: uses and interpretations. Neuroimage. 2010 Sep;52(3):1059-69. doi: 10.1016/j.neuroimage.2009.10.003. Epub 2009 Oct 9.

  PMID: 19819337 BACKGROUND

• Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009 Mar;10(3):186-98. doi: 10.1038/nrn2575. Epub 2009 Feb 4.

  PMID: 19190637 BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Psychotherapy; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities; Behavior Therapy

Study Officials

• Henny Visser, PhD

  GGZ Centraal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The research assessors will be blinded for treatment allocation. Partcipants and clinicians will be requested not to reveal information about treatment allocation to the assessors.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, randomized controlled non-inferiority trial. 203 OCD patients will be recruited. During intake for treatment, patients willing to participate, will be invited for a baseline visit, after the Informed Consent process (IC). Then the patient will be randomized to 20 sessions IBA or 20 sessions CBT. Randomization ratio is 1:1, stratified by site. OCD symptom severity will be assessed by a blind assessor at baseline, after 20 sessions, and 6 and 12 months after posttest. Further, OCD symptom severity and insight in OCD symptoms will be assessed (self-report) weekly. To explore working mechanisms, 43 patients of each treatment arm will receive pre- and posttreatment brain imaging and neuropsychological assessment. After randomization, patients are screened for MRI eligibility, until the sufficient amount of participants is reached. A complementary IC will be signed. 43 healthy controls will receive a single brain imaging and neuropsychological testing session.

Study Record Dates

• First Submitted: April 7, 2019
• First Posted: April 26, 2019
• Study Start: March 20, 2019
• Primary Completion: October 17, 2023
• Study Completion: October 17, 2023
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (7)