The Effect of Celecoxib on Neuroinflammation in MDD

NCT04814355 | Completed Phase 4 FDA Drug

• 1 other identifier: 81741
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) affects an estimated 350 million people worldwide and is a leading contributor to global disease burden. Commonly used monoamine reuptake-inhibiting treatments for depression are suboptimal, resulting in only 30% of patients achieving remission. This may be because monoamine dysfunction is not the primary pathophysiology in all MDD patients. One avenue for the development of novel MDD treatments is through anti-inflammatory drugs; MDD is linked to a pro-inflammatory phenotype characterized by microglial activation, leading to the release of pro-inflammatory cytokines and upregulation of cellular markers including cyclooxygenase-2 (COX-2) and translocator protein (TSPO; a protein located on the outer membrane of microglia). Relevant to this proposal, TSPO can serve as an in vivo marker of neuroinflammation using the newly developed positron emission tomography (PET) tracer for TSPO, \[18F\]FEPPA. In support of this, a recent \[18F\]FEPPA PET study found that MDD patients in a current major depressive episode (MDE) had significantly higher TSPO binding in the prefrontal cortex (PFC), anterior cingulate cortex (ACC) and insula, relative to healthy controls. The prefrontal cortex and ACC are both implicated in mood regulation whereas the insula is involved in interoceptive signaling, which is known to be abnormal in MDD. Celecoxib, a selective COX-2 nonsteroidal anti-inflammatory drug (NSAID), is a promising new treatment for neuroinflammation in MDD. Clinical studies have observed that, in a subset of depressed patients, celecoxib treatment reduced depression severity as assessed by the Hamilton Depression Rating Scale (HDRS). While these findings demonstrate that celecoxib reduces symptom severity, PET imaging technology is critical for understanding how celecoxib affects the underlying pathophysiology of depression. Here, the team will investigate neuroinflammation as an underlying pathology in depression and test whether neuroinflammation is reduced by celecoxib in MDD patients. Specifically, in the proposed pilot study, MDD patients in a current MDE will receive \[18F\]FEPPA PET scans prior to and following 8 weeks of treatment with 400mg/day of celecoxib, with HDRS scores obtained at each time point. The investigators hypothesize that following celecoxib treatment, patients will show a significant reduction in neuroinflammation in the PFC, ACC and insula, which will correlate positively with the reduction in depressive symptoms, as measured by the HDRS. The proposed study will use novel imaging technology, \[18F\]FEPPA PET, to measure the effects of celecoxib on neuroinflammation in MDD patients. Our results will help to 1) identify neuroinflammation as an underlying pathology in MDD and 2) test whether reduction of inflammation is the mechanism of action of celecoxib. As such, the results of this study will aid in the development of targeted clinical treatments to improve remission rates in MDD patients.

Conditions

Major Depressive Disorder; Neuroinflammation

Keywords

PET; Major Depressive Disorder; Neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Change in neuroinflammation as measured by [18F]FEPPA PET.

  Change in \[18F\]FEPPA VT (VT; volume of distribution: ratio of the concentration of radioligand in tissue to that in plasma at equilibrium)

  Before and after 8 weeks of treatment with celecoxib.

Secondary Outcomes (1)

• Change in Hamilton Depression Rating Scale-17 (HAMD) score.

  Before and after 8 weeks of treatment with celecoxib.

Study Arms (1)

Celecoxib 400 mg

EXPERIMENTAL

Patients will receive 400 mg/day of celecoxib for 8 weeks.

Drug: Celecoxib 400 mg

Interventions

Celecoxib 400 mg DRUG

Patients will receive 400 mg/day of celecoxib for 8 weeks.

Also known as: celebrex

Celecoxib 400 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-65
• Diagnosis of MDD and currently in a major depressive episode
• Capacity to give informed consent
• Score of at least 29 on the MADRS

You may not qualify if:

• Low affinity binders (LABs) for TSPO Genotype
• Hypersensitivity to celecoxib, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; previous asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Heptic impairment, heart failure, severe renal impairment, recent GI bleed, history of peptic ulcer disease, anemia or any other contraindication for celecoxib
• Poor CYP2C9 metabolizer
• Currently taking medications that interact with celecoxib (digoxin, antihypertensives, diuretics, anticoagulant or anti-platelet treatment, including aspirin)
• Use of herbs, drugs, or medications with anti-inflammatory or immunomodulatory properties (within 5 half-lives of starting celecoxib treatment)
• Unlikely to tolerate medication washout or the medication-free period following washout
• Participant considered at significant risk for suicide
• ECT within 1 month
• High potential for excessive drug/alcohol use during the treatment period (excluding nicotine or cannabis)
• Significant active physical illness or neurological deficit that may affect brain functioning or imaging
• Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is currently pregnant, breastfeeding, or planning to conceive during the course of study participation

Sponsors & Collaborators

• Brain & Behavior Research Foundation: collaborator
• Stony Brook University: lead

Study Sites (1)

Psychiatry Department at Stony Brook University

Stony Brook, New York, 11794-8101, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Neuroinflammatory Diseases

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christine DeLorenzo, PhD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 22, 2021
• First Posted: March 24, 2021
• Study Start: August 1, 2018
• Primary Completion: August 11, 2025
• Study Completion: February 28, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)