Neuroinflammation in Patients With OCD

Sponsor

New York State Psychiatric Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04786548

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to examine whether measurements of inflammation from brain scanning and blood tests can predict how much benefit patients with obsessive-compulsive disorder (OCD) will have from treatment with an anti-inflammatory medication, celecoxib, when adding to ongoing medication-based treatment for OCD.

Condition or Disease	Intervention/Treatment	Phase
Obsessive-Compulsive Disorder	Drug: Celecoxib	Phase 2

Detailed Description

Existing evidence-based treatments for adults with obsessive-compulsive disorder (OCD), including cognitive behavioral therapy and first-line medication-based treatment, do not fully resolve symptoms for a majority of patients. This study proposes to test a new treatment strategy for OCD, examining inflammation as one factor that may contribute to the development of OCD and that may be targeted with medication-based treatment. Recent findings using both brain imaging and analyses from blood samples suggest that some individuals with OCD have increased levels of inflammation in the brain, which may have negative effects on brain function, contributing to symptoms of OCD. Moreover, early clinical studies suggest that some medications with anti-inflammatory properties may be beneficial in treating OCD symptoms. An important and untested question is whether the degree of inflammation assessed using these biological tools can predict how much benefit individuals with OCD will derive from treatment with an anti-inflammatory medication. The investigators will measure inflammation in the brain using PET imaging and measures of inflammation in the body using blood tests in adults with OCD. Patients will then undergo 8 weeks of treatment with an anti-inflammatory medication with some evidence of clinical effectiveness in OCD, celecoxib. The investigators predict that OCD patients with greater evidence of inflammation at baseline, assessed by brain imaging and blood tests, will derive the greatest benefit from anti-inflammatory treatment. In addition, the investigators will compare these inflammatory markers with data from a group of healthy volunteers (collected as part of another protocol, IRB #6786), to extend earlier work finding elevated inflammatory markers in adult OCD. Finally, the investigators will examine whether celecoxib treatment in OCD patients results in reductions in measures of inflammation measured from blood samples and whether the degree of anti-inflammatory effect observed biologically is related to improvement in OCD symptoms. The ultimate goal of this line of research is to pave the way for more individually-tailored, effective treatments for adult OCD based on improved understandings of pathological targets, and to validate an anti-inflammatory approach to the treatment of OCD in individuals with evidence of inflammation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

21 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Precision Medicine Approach to OCD Treatment: Targeting Neuroinflammation

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Celecoxib Treatment Patients will receive standardized pharmacotherapy with celecoxib 100mg twice daily for the first week, and will then, if well-tolerated, will be increased to 200mg twice daily for the next seven weeks. Visits with the study psychiatrist will occur weekly for the first four weeks, and biweekly thereafter until week 8, which will be conducted remotely in general, although they may be conducted in-person as clinically warranted and may be conducted in person on the days of other in-person visits. If individuals experience significant side-effects from a given dose, the treating physician may lower the medication dose according to clinical judgment; if side-effects are intolerable, we will discontinue the research procedures and advance to open clinical treatment	Drug: Celecoxib Patients will receive standardized pharmacotherapy with celecoxib 100mg twice daily for the first week, and will then, if well-tolerated, will be increased to 200mg twice daily for the next seven weeks. Other Names: Celebrex

Arm

Intervention/Treatment

Experimental: Celecoxib Treatment

Patients will receive standardized pharmacotherapy with celecoxib 100mg twice daily for the first week, and will then, if well-tolerated, will be increased to 200mg twice daily for the next seven weeks. Visits with the study psychiatrist will occur weekly for the first four weeks, and biweekly thereafter until week 8, which will be conducted remotely in general, although they may be conducted in-person as clinically warranted and may be conducted in person on the days of other in-person visits. If individuals experience significant side-effects from a given dose, the treating physician may lower the medication dose according to clinical judgment; if side-effects are intolerable, we will discontinue the research procedures and advance to open clinical treatment

Drug: Celecoxib

Other Names:

Celebrex

Outcome Measures

Primary Outcome Measures

Yale-Brown Obsessive Compulsive Scale [Week 8]
The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a clinician-administered interview that measures the presence and severity of symptoms of Obsessive-Compulsive Disorder. It consists of 10 questions with scores ranging from 0 to 4, with a possible score ranging from 0 to 40. The primary measure of clinical improvement in this study is the Week 8 YBOCS score. In statistical models, we will co-vary for the Week 0 YBOCS score to account for baseline symptoms severity, but the Week 8 value is the primary outcome.

Secondary Outcome Measures

TSPO Volume of Distribution assessed by PET imaging with [11C]ER-176 [Baseline]
We will perform PET imaging with the [11C]ER-176 radiotracer to quantify TSPO binding, a marker of neuroinflammation, quantified as the outcome measure Volume of Distribution (VT).
MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel [Baseline]
This assay from Millipore Sigma simultaneously quantifies 41 cytokine and chemokine biomarkers from serum.
MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel [Week 8]
This assay from Millipore Sigma simultaneously quantifies 41 cytokine and chemokine biomarkers from serum.
PGE2 [Baseline]
prostaglandin E2 levels will be measured in serum.
PGE2 [Week 8]
prostaglandin E2 levels will be measured in serum.
PGF2-alpha [Week 0]
Prostaglandin F2-alpha levels will be measured in serum.
PGF2-alpha [Week 8]
Prostaglandin F2-alpha levels will be measured in serum.
CRP [Week 0]
C-reactive protein levels will be measured in serum.
CRP [Week 8]
C-reactive protein levels will be measured in serum.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 to 55 years old
Principal diagnosis of Obsessive-Compulsive Disorder (OCD)
Ongoing OCD symptoms despite current treatment with psychiatric medication
Capacity to provide informed consent

Exclusion Criteria:

Psychiatric comorbidities that would increase risk of participation or impact research measures (e.g., suicidality)
Medical or neurological conditions that would increase risk of participation or impact research measures
Contraindications to an MRI or PET scan (e.g., metal implants)
Current use of medications that may interact with study drug or impact research measures (e.g., antipsychotics, corticosteroids, immunosuppressant medications, or daily non-steroidal anti-inflammatory medications)
Starting a new evidence-based therapy for OCD (e.g., exposure with response prevention) 4 weeks prior to study enrollment