Treating Immuno-metabolic Depression With Anti-inflammatory Drugs

NCT05415397 | Active Not Recruiting Phase 3

• 1 other identifier: NL79765.029.21
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

As the role of (neuro)inflammation in depression is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs such as celecoxib has shown encouraging preliminary results. However, inflammation is not present in all depressed patients. Depression is heterogeneous: patients express diverse and sometimes opposing symptoms and biological profiles. The investigators of the present trial recently introduced the concept of ImmunoMetabolic Depression (IMD), characterized by the clustering of inflammatory/metabolic dysregulations and atypical, energy-related symptoms (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis), and present in approximately 30% of cases. Converging evidence suggests that in this subgroup of depression cases, inflammation may exert a crucial pathobiological mechanism, representing therefore an actionable therapeutic target. In this trial IMD will be applied as a tool to personalize treatment, by matching depressed subjects with IMD with a targeted anti-inflammatory add-on treatment. In this study, 140 persons with IMD will be selected. In this specific group of patients, the investigators will test whether celecoxib add-on (400 mg/d) is more effective than placebo in the treatment of depression through a 12-week double-blind, randomized (1:1), placebo-controlled trial. By selecting specifically depressed patients with IMD, the proposed treatment selectively targets key inflammatory pathophysiological pathways to enhance clinical outcome for depression. This personalized approach is expected to lead to large health gains for a sizable proportion of patients. The main hypothesis is that the group of patients with IMD receiving TAU + celecoxib, as compared to the TAU + placebo, will show a better symptom course over the 12-week follow-up.

Conditions

Depressive Disorder, Major; Inflammation

Keywords

INFLAMED; Depression; Inflammation; Immuno-metabolic Depression; Celecoxib

Outcome Measures

Primary Outcomes (1)

• Depressive symptoms severity

  Depressive symptoms severity measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR; score ranging from 0 to 84, higher scores indicate higher severity of depressive symptoms). Trajectories of depressive symptoms will be modeled via mixed models including bi-weekly assessments

  12 weeks

Secondary Outcomes (3)

• Number of participants achieving Response

  12 weeks

• Number of participants achieving Remission

  12 weeks

• Symptom profile: atypical, energy-related depressive symptoms (AES)

  12 weeks

Other Outcomes (10)

• Fatigue

  12 weeks

• Food craving

  12 weeks

• Daytime sleepiness

  12 weeks

Study Arms (2)

Celecoxib

EXPERIMENTAL

Celecoxib 400 mg/day, 2 capsules (200 mg) daily, 12 weeks

Drug: Celecoxib 400mg

Placebo

PLACEBO COMPARATOR

Placebo, 2 capsules daily, 12 weeks

Drug: Placebo

Interventions

Celecoxib 400mg DRUG

Celecoxib add-on (400mg daily) add-on to treatment as usual (standard antidepressant treatment)

Also known as: Celecoxib, ATC M01AH01

Celecoxib

Placebo DRUG

Placebo add-on to treatment as usual (standard antidepressant treatment)

Placebo

Eligibility Criteria

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

You may qualify if:

• DSM-5 diagnosis of MDD confirmed with clinical interview (MINI-S voor DSM-5 Nederlandse versie 2019)
• Currently using pharmacotherapy (e.g., SSRI, SNRI, TCA, TetraCA, MAOI, other antidepressant \[bupropion, vortioxetine, agomelatine\])) and/or psychotherapy. Subjects should be on the current treatment for at least 4 weeks
• IDS-SR score ≥26 (moderate to severe depressive symptoms) and a score ≥6 on atypical, energy-related symptoms scale from IDS
• CRP \> 1mg/L
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: 1) is not a woman of child bearing potential (WOCBP); 2) Is a WOCBP and agrees to use, or is already using, a contraceptive method during the intervention period and up to 1 month after the intervention
• Signed informed consent

You may not qualify if:

• Contraindications for celecoxib (history of: peptic ulcers, gastrointestinal bleeding, ischemic heart disease, stroke, heart failure, allergic reactions to aspirin/NSAIDs/coxibs; impaired kidney function (creatinine clearance \< 30 ml/min), impaired liver function (ALT \> 2x ULT)
• ECT in the past 3 months
• Being on other psychotropic drugs
• Clinically overt alcohol/drug dependence or other primary psychiatric diagnoses (schizophrenia, schizoaffective, OCD, or bipolar disorder)
• Chronic use of anti-inflammatory drugs and corticosteroids
• Current use of anticoagulants
• Not speaking Dutch

Sponsors & Collaborators

• Netherlands Brain Foundation: collaborator
• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Department of Psychiatry Amsterdam UMC

Amsterdam, 1081 HJ, Netherlands

Location

Related Publications (10)

• Milaneschi Y, Lamers F, Berk M, Penninx BWJH. Depression Heterogeneity and Its Biological Underpinnings: Toward Immunometabolic Depression. Biol Psychiatry. 2020 Sep 1;88(5):369-380. doi: 10.1016/j.biopsych.2020.01.014. Epub 2020 Jan 28.

  PMID: 32247527 RESULT

• Lamers F, Milaneschi Y, Vinkers CH, Schoevers RA, Giltay EJ, Penninx BWJH. Depression profilers and immuno-metabolic dysregulation: Longitudinal results from the NESDA study. Brain Behav Immun. 2020 Aug;88:174-183. doi: 10.1016/j.bbi.2020.04.002. Epub 2020 Apr 6.

  PMID: 32272220 RESULT

• Penninx BW, Milaneschi Y, Lamers F, Vogelzangs N. Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile. BMC Med. 2013 May 15;11:129. doi: 10.1186/1741-7015-11-129.

  PMID: 23672628 RESULT

• Milaneschi Y, Kappelmann N, Ye Z, Lamers F, Moser S, Jones PB, Burgess S, Penninx BWJH, Khandaker GM. Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts. Mol Psychiatry. 2021 Dec;26(12):7393-7402. doi: 10.1038/s41380-021-01188-w. Epub 2021 Jun 16.

  PMID: 34135474 RESULT

• Kohler O, Benros ME, Nordentoft M, Farkouh ME, Iyengar RL, Mors O, Krogh J. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014 Dec 1;71(12):1381-91. doi: 10.1001/jamapsychiatry.2014.1611.

  PMID: 25322082 RESULT

• Kohler-Forsberg O, N Lydholm C, Hjorthoj C, Nordentoft M, Mors O, Benros ME. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand. 2019 May;139(5):404-419. doi: 10.1111/acps.13016. Epub 2019 Mar 28.

  PMID: 30834514 RESULT

• Osimo EF, Baxter LJ, Lewis G, Jones PB, Khandaker GM. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels. Psychol Med. 2019 Sep;49(12):1958-1970. doi: 10.1017/S0033291719001454. Epub 2019 Jul 1.

  PMID: 31258105 RESULT

• Baune BT, Sampson E, Louise J, Hori H, Schubert KO, Clark SR, Mills NT, Fourrier C. No evidence for clinical efficacy of adjunctive celecoxib with vortioxetine in the treatment of depression: A 6-week double-blind placebo controlled randomized trial. Eur Neuropsychopharmacol. 2021 Dec;53:34-46. doi: 10.1016/j.euroneuro.2021.07.092. Epub 2021 Aug 8.

  PMID: 34375789 RESULT

• Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ. Inflammation and clinical response to treatment in depression: A meta-analysis. Eur Neuropsychopharmacol. 2015 Oct;25(10):1532-43. doi: 10.1016/j.euroneuro.2015.06.007. Epub 2015 Jun 20.

  PMID: 26169573 RESULT

• Zwiep JC, Bet PM, Rhebergen D, Nurmohamed MT, Vinkers CH, Penninx BWJH, Milaneschi Y, Lamers F. Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial. Brain Behav Immun Health. 2022 Dec 30;27:100585. doi: 10.1016/j.bbih.2022.100585. eCollection 2023 Feb.

  PMID: 36655056 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation; Depression

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

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

• Yuri Milaneschi, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Femke Lamers, PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 12-week double-blind, randomized (1:1), placebo-controlled trial comparing celecoxib add-on (400 mg/d) versus placebo add-on to TAU in the treatment of 140 subjects with MDD and Immuno-metabolic Depression features

Study Record Dates

• First Submitted: June 3, 2022
• First Posted: June 13, 2022
• Study Start: September 28, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following study closure and publication of the main results, no end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose

Locations

NL (1)