Neuroinflammation in Patients With OCD

A Precision Medicine Approach to OCD Treatment: Targeting Neuroinflammation

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.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder
• Intervention / Treatment: Drug: Celecoxib

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 Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gabriella Restifo-Bernstein, BS; Phone Number: (646) 774-8138; Email: gabriella.restifo@nyspi.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale-Brown Obsessive Compulsive Scale	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.	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TSPO Volume of Distribution assessed by PET imaging with [11C]ER-176	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).	Baseline
MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel	This assay from Millipore Sigma simultaneously quantifies 41 cytokine and chemokine biomarkers from serum.	Baseline
MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel	This assay from Millipore Sigma simultaneously quantifies 41 cytokine and chemokine biomarkers from serum.	Week 8
PGE2	prostaglandin E2 levels will be measured in serum.	Baseline
PGE2	prostaglandin E2 levels will be measured in serum.	Week 8
PGF2-alpha	Prostaglandin F2-alpha levels will be measured in serum.	Week 0
PGF2-alpha	Prostaglandin F2-alpha levels will be measured in serum.	Week 8
CRP	C-reactive protein levels will be measured in serum.	Week 0
CRP	C-reactive protein levels will be measured in serum.	Week 8

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: Jeffrey Miller, M.D., New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 3, 2021
• First Posted (Actual): March 8, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: OCD; Celecoxib; Neuroinflammation; Obsessive-Compulsive Disorder; Nonsteroidal anti-inflammatory drug
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Inflammation; Personality Disorders; Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Neuroinflammatory Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: 8115

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No