Neurobiological Markers of Treatment Response for Anxiety and OCD

Obsessive-compulsive disorder (OCD) and anxiety disorders are common and debilitating conditions which are often chronic when treatment is not provided. International guidelines recommend cognitive behavioral therapy (CBT) as the first-line treatment, and research has shown that CBT can be delivered over a concentrated period of time. The Bergen 4-Day Treatment (B4DT) is an exposure-based treatment which is delivered over four consecutive days. B4DT has been shown to induce rapid and long-lasting remission in around 70% of patients. This provides a platform for studying psychological and neurobiological changes associated with treatment response and non-response. The present study will investigate longitudinal changes in psychological measures and DNA methylation in patients who receive the B4DT, as well as a subset will also undergo multimodal brain imaging.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder; Social Anxiety Disorder; Panic Disorder
• Intervention / Treatment: Behavioral: Bergen 4-Day Treatment (B4DT)

Detailed Description

The primary study will include 500 OCD patients who will receive the B4DT. Symptom severity will be prospectively measured before treatment, approximately 10 days after treatment and three months after treatment. Saliva samples will be collected for later extraction of DNA methylation during the first day of treatment, the last day of treatment, and three months after treatment. A substudy will use multimodal magnetic resonance imaging (MRI) before treatment, approximately 10 days after treatment and three months after treatment. The substudy will also 100 patients with social anxiety disorder or panic disorder for DNA methylation and MRI, as well as 50 healthy controls for MRI. Clinical data will be collected from a consent-based quality register ("Kvalitetsregister for konsentrerte behandlingsformat").

The aim of the study is to investigate changes in DNA methylation as well as functional and structural brain networks that occur in patients undergoing B4DT, and to correlate these changes with immediate and long-term response to treatment.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Bjarne Hansen, PhD; Phone Number: +4792090765; Email: bjarne.kristian.aaslie.hansen@helse-bergen.no

Study Locations

• Norway
  • Vestland
    • Bergen, Vestland, Norway, 5009
      • Recruiting
      • Bergen Center for Brain Plasticity
      • Contact: Bjarne Hansen, PhD; Phone Number: +4792090765; Email: bjarne.kristian.aaslie.hansen@helse-bergen.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study includes patients with OCD, panic disorder or social anxiety disorder which will receive the Bergen 4-Day Treatment (B4DT) in Norway. Healthy controls are also recruited for the MRI substudy

Description

Inclusion Criteria:

• Diagnosed with obsessive-compulsive disorder, panic disorder or social anxiety disorder using DSM-5 criteria
• Referred to National Clinic for 4-Day Treatment, Haukeland University Hospital, Bergen, Norway
• Consented to participate in the "Kvalitetsregister for konsentrerte behandlingsformat"

Exclusion Criteria:

• Suicidal, ongoing mania, primary eating disorder, intellectual disability, ongoing psychosis, ongoing substance abuse

For MRI substudy:

Inclusion Criteria:

- For the healthy controls, no previous or current psychiatric disorders as detected by the Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria:

- MRI incompatibility (e.g. pregnancy, metal implants)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with obsessive-compulsive, social anxiety or panic disorder; Patients with obsessive-compulsive disorder. The MRI substudy will also include patients with social anxiety or panic disorder	Behavioral: Bergen 4-Day Treatment (B4DT); A concentrated and exposure-based psychological treatment over four consecutive days
For MRI substudy: Healthy controls; Healthy controls demographically matched to the patient group on age, sex and years of education

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Symptom severity of obsessive-compulsive disorder	Before treatment
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Symptom severity of obsessive-compulsive disorder	approximately 10 days after treatment
Yale-Brown Obsessive Compulsive Scale (Y-BOCS)	Symptom severity of obsessive-compulsive disorder	three months after treatment
Panic Disorder Severity Scale (PDSS)	Symptom severity of panic disorder	Before treatment
Panic Disorder Severity Scale (PDSS)	Symptom severity of panic disorder	approximately 10 days after treatment
Panic Disorder Severity Scale (PDSS)	Symptom severity of panic disorder	three months after treatment
Liebowitz Social Anxiety Scale (LSAS)	Symptom severity of social anxiety disorder	Before treatment
Liebowitz Social Anxiety Scale (LSAS)	Symptom severity of social anxiety disorder	approximately 10 days after treatment
Liebowitz Social Anxiety Scale (LSAS)	Symptom severity of social anxiety disorder	three months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA Methylation	Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system	Before treatment
DNA Methylation	Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system	approximately 10 days after treatment
DNA Methylation	Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system	three months after treatment
Magnetic Resonance Imaging	Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls	Before treatment
Magnetic Resonance Imaging	Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls	approximately 10 days after treatment
Magnetic Resonance Imaging	Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls	three months after treatment

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Harvard Medical School (HMS and HSDM); University of Oslo; Oslo University Hospital; University of Bergen; University of North Carolina, Chapel Hill; Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Bjarne Hansen, PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2018
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): December 11, 2027

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Estimate): December 23, 2022

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: MRI; genetics; epigenetics
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Phobic Disorders; Disease; Obsessive-Compulsive Disorder; Anxiety Disorders; Phobia, Social; Panic Disorder
• Other Study ID Numbers: BCBP-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No