Fear Extinction and Mechanisms of Change in Obsessive Compulsive Disorder

NCT02467374 | Completed DMC

• 1 other identifier: 2014P002325
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out more about how the brain stores emotional learning in obsessive-compulsive disorder (OCD). In particular, we would like to understand how human beings learn not to fear. We are also interested in learning about how behavioral therapy (BT) for OCD affects emotional learning in the brain. We hope this study will help us understand why people with OCD cannot control unwanted fear and to develop better treatments for adults with OCD. Patients will be randomly assigned (like the flip of a coin) to receive 12 weeks of BT or 12 weeks of waitlist, followed by 12 weeks of BT. We are seeking individuals 18-60 with OCD and individuals with no psychiatric history. Participation includes a diagnostic evaluation, 12 weeks of BT or 12 weeks of waitlist followed by BT, questionnaires, and up to six (6) MRI scans. You may receive up to $500 for your participation and reimbursement for parking.

Conditions

Obsessive Compulsive Disorder

Keywords

OCD; Neuroimaging; Fear Extinction; Behavior Therapy

Outcome Measures

Primary Outcomes (1)

• Obsessive compulsive symptoms as measured by Yale-Brown Obsessive Compulsive Scale (Y-BOCS)

  We assesed reduction in OCD symptom severity over a 24 week period. Efficacy was again compared in the follow-up phase of the study in from week 24 to week 36.

  24-36 weeks

Other Outcomes (2)

• Fear Conditioning/Extinction Paradigm

  24-36 weeks

• Skin Conductance

  24-36 weeks

Study Arms (2)

Immediate Behavior Therapy

ACTIVE COMPARATOR

If assigned to the immediate BT condition, patients will be asked to make about 24 visits to our clinics at MGH, including an initial assessment, 12 therapy visits over 12 weeks, and 1 booster session (Week 16). Patients will be asked to come to the clinic for assessments during weeks 4 and 6 and after the treatment (week 12), as well as 1 follow-up visit (week 24). Additionally, patients will participate in 6 MRI scanning sessions at the Charlestown Navy Yard.

Behavioral: Behavior Therapy

Waitlist Behavior Therapy

ACTIVE COMPARATOR

Patients will wait for 12 weeks before starting BT. In this case, they will be asked to make about 21 visits to our clinics, including an initial assessment visit, 12 therapy visits, and 1 booster session. Patients will be asked to come to the clinic for assessments during (weeks 4 and 6) and after the waiting period (week 12). Additionally, patients will participate in 6 MRI scanning sessions at the Charlestown Navy Yard.

Behavioral: Behavior Therapy

Interventions

Behavior Therapy BEHAVIORAL

BT for OCD focuses primarily on "exposure with response prevention (ERP)." "ERP" involves gradual exposure to anxiety-provoking situations (things or situations that frighten or disturb some people), and will help to prevent compulsions (repetitive behaviors).

Also known as: Exposure and Response Prevention

Immediate Behavior Therapy; Waitlist Behavior Therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Outpatient men and women age 18 to 60, proficient in English, and able to give informed consent
• For OCD patients only: Primary OCD that causes at least moderate distress and/or impairment (Y-BOCS total score \> 16)

You may not qualify if:

• Current clinically significant suicidality and/or BDI-II suicide item (#9) score \>1
• Current or history of neurologic or psychiatric disease (e.g., mental retardation, dementia, brain damage, or other cognitive impairment) that would interfere with ability to engage in BT
• Psychopathology not appropriate for the treatment (such as substance abuse or dependence within the past 3 months; current manic episode; psychosis)
• Previous treatment with ≥4 sessions of BT for OCD
• Currently receiving any other psychotherapy or planning to initiate such treatment during the study
• Use of conventional antipsychotic medications or medications that would lower seizure threshold in high doses or may otherwise affect cerebral metabolism (other than to those required for stabilization of OCD).
• Use of benzodiazepines within 2 weeks prior to study is not allowed. Use of other psychotropic medications (e.g., SSRIs and atypical antipsychotics) will be allowed provided the dose has been stable for \> 8 weeks. Planning on initiation or dose change of psychotropic medication during the study.
• Impaired (or uncorrected) vision, medical illness, or medical treatment that would likely interfere with participation.
• History of head injury resulting in prolonged loss of consciousness and/or neurological sequelae; History of seizures; History of stroke; Signs of increased intracranial pressure; Prior neurosurgical procedure
• Metal in the body, metal injury to the eyes; Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt
• Pregnancy; breastfeeding or nursing; if the patient cannot rule out the possibility of pregnancy, a pregnancy test (to be ruled out by urine ß-HCG) will be conducted prior to study
• Weight \> 250 lbs

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Jacoby RJ, Greenberg JL, Hurtado A, Pedersen W, Ellard KK, Pace-Schott EF, Oliver KI, Milad MR, Wilhelm S, Camprodon JA. Neural mechanisms underlying exposure and response prevention for obsessive compulsive disorder: A randomized controlled trial. Behav Res Ther. 2025 Nov;194:104858. doi: 10.1016/j.brat.2025.104858. Epub 2025 Sep 17.

  PMID: 41005270 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Behavior Therapy

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Sabine Wilhelm, Ph.D.

  Massachusetts General Hospital: Department of Psychiatry

  PRINCIPAL INVESTIGATOR

• Mohammed Milad, Ph.D.

  Massachusetts General Hospital: Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sabine Wilhelm, PhD, Chief of Psychology

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 10, 2015
• Study Start: December 1, 2014
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: March 31, 2022

Record last verified: 2022-03

Locations

US (1)