Clinical trial NCT02437773: Neurocircuit Mechanisms of OCD Across the Lifespan
Official title: Neurocircuit Mechanisms of OCD Across the Lifespan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obsessive-Compulsive Disorder
Keywords: OCD
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2015-05-08
Enrollment: 206
Sex: ALL
Minimum age (years): 13
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obsessive-compulsive disorder (OCD), characterized by intrusive thoughts (obsessions) and related behavioral rituals (compulsions), is a common psychiatric illness that often emerges in childhood and causes life-long disability in over 50% of patients. Psychological theory suggests that OCD symptoms are driven by a person's difficulty disengaging their feelings from simple tasks (e.g. washing hands, locking a door) due to excessive anxiety about performance errors. Cognitive behavioral therapy (CBT), the gold standard treatment for OCD, repeatedly exposes patients to their OCD-stressor until this anxiety is reduced. While CBT is typically more effective in teenagers than adults, patients from both age groups are usually left with residual symptoms, highlighting the need for better treatments. In this study, CBT will be studied in both teen-aged and adult patients. Two groups, both with childhood onset OCD, will be randomized to either CBT for OCD or stress management training (SMT), an active therapy but with minimal effects on OCD symptoms. The investigators will also study age-matched, healthy controls as comparison subjects.

Before and after 12 weeks of CBT, all subjects will undergo functional Magnetic Resonance Imaging (fMRI) scans to see what regions of the brain become active when a concentration task is performed and how that activation is changed after CBT. The purpose of this study is to demonstrate the brain changes associated with CBT treatment and how differences in these changes in teenage compared to adult patients may drive differences in CBT response.

Detailed description: While the study itself is of parallel design for its data-collection and measurement purpose, it is listed as a partial-crossover design in the IRB-approved protocol because subjects randomized to the SMT group are given the option of entering 12-weeks of CBT sessions after all of their SMT data collection. To understand brain changes that occur with CBT compared to SMT in both age groups, the investigators will collect fMRI data before and after therapy. Some limited data will be collected in patients who are initially randomized to SMT but then opt to crossover to CBT. fMRI data will also be collected in healthy teens and adults before and after 12 weeks (but without intervening therapy) to allow the investigators to control for the simple effects of time that may cause brain changes that are not related to therapy.

Eligibility criteria: Inclusion Criteria for all OCD Subjects \& Healthy Volunteers:

* Male or female
* Age 13-17 (inclusive) subjects diagnosed with OCD, age of onset before 15 years
* Age 25-45 (inclusive) subjects diagnosed with OCD, age of onset before 15 years
* Age 13-17 (inclusive) year old healthy volunteers
* Age 25-45 (inclusive) year old healthy volunteers
* OCD adolescent and adult subjects can be on medications but will have to be on a stable medication regimen for at least 4 weeks prior to enrolling.
* Able and willing to give informed consent
* Ability to tolerate small, enclosed spaces without anxiety

Exclusion Criteria for OCD Subjects:

* Anyone between the ages of 18-24 (inclusive range)
* No lifetime diagnosis of bipolar or psychosis disorders
* Age of OCD onset after 15 years old
* No substance/alcohol abuse in the past 6 months
* No lifetime history of substance/alcohol dependence
* No evidence of suicidal intentions or behaviors in the past 6 months
* No history of serious medical or neurological illness
* No history of closed head injury (e.g. loss of consciousness)
* Pregnant or trying to become pregnant

Additional Exclusion Criteria for Healthy Volunteers:

* No history of past or current mental illness
* Not taking any medication, prescription or non-prescription, with psychotropic effects
* First-degree family members with OCD or tic disorders

Primary outcomes:
measure: Brain activity as assessed by Magnetic Resonance Imaging (fMRI) scans
timeFrame: Baseline to 12-weeks
Secondary outcomes:
measure: OCD symptom severity measured by the Yale Brown Obsessive Compulsive Scale for adults or the Child Yale Brown Obsessive Compulsive Scale for adolescents.
timeFrame: Baseline to 12-weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan, Dept of Psychiatry
name: Kate Fitzgerald, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rueppel M, Mannella KA, Fitzgerald KD, Schroder HS. Post-error slowing in anxiety and obsessive-compulsive disorders. Cogn Affect Behav Neurosci. 2022 Jun;22(3):610-624. doi: 10.3758/s13415-021-00976-9. Epub 2021 Dec 29.
citation: Norman LJ, Mannella KA, Yang H, Angstadt M, Abelson JL, Himle JA, Fitzgerald KD, Taylor SF. Treatment-Specific Associations Between Brain Activation and Symptom Reduction in OCD Following CBT: A Randomized fMRI Trial. Am J Psychiatry. 2021 Jan 1;178(1):39-47. doi: 10.1176/appi.ajp.2020.19080886. Epub 2020 Aug 28.