INflammation-based Stratification for Immune-Targeted Augmentation in Major Depressive Disorder

NCT05644301 | Recruiting Phase 3

• 1 other identifier: T001222N
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 3

Brief Summary

This is a randomised, double-blind, placebo-controlled clinical trial in which patients with major depressive disorder will receive augmentation through minocycline (MCO), celecoxib (CXB) or placebo.

Conditions

Major Depressive Disorder; Inflammation

Keywords

Immunopsychiatry; Celecoxib; Minocyclin; Inflammation; Randomised Controlled Clinical Trial

Outcome Measures

Primary Outcomes (2)

• Change in depressive symptom severity (HDRS-17)

  Change in severity of depression measured as the change in the 17-point scale of the Hamilton Depression Rating Scale (HDRS-17; score is ranging from 0 to 52, higher scores indicate higher severity of depressive symptoms) between baseline and endpoint

  T0 -> T6 (12 weeks)

• Remission rate of depression (HDRS-17)

  Rates of remission measured as a score of ≤7 on the 17-point scale of the Hamilton Depression Rating Scale (HDRS-17; score is ranging from 0 to 52, higher scores indicate higher severity of depressive symptoms and scores 0-7 are considered as being normal) at endpoint

  T0 -> T6 (12 weeks)

Secondary Outcomes (11)

• Change in depressive symptom severity (IDS-30SR)

  T0 -> T6 (12 weeks)

• Response rate of depressive symptoms (HDRS-17)

  T0 -> T6 (12 weeks)

• Change in night-time sleep (PSQI)

  T0 -> T6 (12 weeks)

• Change in anxiety (STAI)

  T0 -> T6 (12 weeks)

• Change in core assessment of psychomotor change (CORE)

  T0 -> T6 (12 weeks)

Other Outcomes (4)

• Immune markers

  T0 -> T6 (12 weeks)

• Alternate immune markers

  T0 -> T6 (12 weeks)

• Tryptophan pathway metabolites

  T0 -> T6 (12 weeks)

Study Arms (6)

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Minocyclin + Treatment As Usual (TAU)

ACTIVE COMPARATOR

Drug: Minocyclin

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Celecoxib + Treatment As Usual (TAU)

ACTIVE COMPARATOR

Drug: Celecoxib

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Placebo + Treatment As Usual (TAU)

PLACEBO COMPARATOR

Drug: Placebo

High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Minocyclin + Treatment As Usual (TAU)

ACTIVE COMPARATOR

Drug: Minocyclin

High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Celecoxib + Treatment As Usual (TAU)

ACTIVE COMPARATOR

Drug: Celecoxib

High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Placebo + Treatment As Usual (TAU)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Celecoxib DRUG

Oral capsule, 200 mg, twice daily, for 12 weeks

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Celecoxib + Treatment As Usual (TAU); High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Celecoxib + Treatment As Usual (TAU)

Minocyclin DRUG

Oral capsule, 100 mg, twice daily, for 12 weeks

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Minocyclin + Treatment As Usual (TAU); High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Minocyclin + Treatment As Usual (TAU)

Placebo DRUG

Oral capsule, no active substance, twice daily, for 12 weeks

High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Placebo + Treatment As Usual (TAU); High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Placebo + Treatment As Usual (TAU)

Eligibility Criteria

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

You may qualify if:

• Male or female, 18-65 years inclusive.
• Able and willing to give informed consent and take oral medication.
• Physically healthy.
• Diagnosis of Major Depressive Disorder by DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI).
• The current episode of depression has failed to remit to the current antidepressant treatment at the adequate dose (as defined in the Maudsley Prescribing guidelines). Relapse while taking an antidepressant is also considered a treatment failure.
• Tolerant to the current antidepressant and having no planned changes in their current therapy for the duration of the study.
• Stable on current treatment for a minimum of 4 weeks (6 weeks for fluoxetine) prior to baseline.
• If female and of childbearing age, willing to use adequate contraceptive precautions and willing to take a pregnancy test at baseline.

You may not qualify if:

• Primary diagnosis of a bipolar disorder, psychotic spectrum disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or alcohol and/or substance use disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (\< 4 weeks before screening, excl. nicotine and caffeine).
• Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.).
• History of peptic ulcer disease or gastrointestinal (GI) bleeding.
• Having an acute infection or inflammatory bowel disorder.
• Current severe cardiovascular disease, congestive heart failure (NYHA-class II-IV), ischemic or thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery),
• Liver impairment (alanine aminotransferase \> 2x upper limit, serum albumin \< 25 g/l or Child-Pugh Score ≥ 10)
• Renal impairment (creatinine clearance \< 30 mL/min).
• Having received \>14 days of tetracycline or non-steroidal anti-inflammatory medication within the previous 2 months, or having a history of sensitivity or intolerance to these classes of drugs.
• Chronic severe hypertension (systolic BP \> 170 mmHg).
• Serology positive for hepatitis-B surface antigen, hepatitis-C antibodies or HIV antibodies.
• Received electroconvulsive therapy \< 2 months prior to screening.
• Blood donation in 30 days prior to screening.
• Pregnancy or breastfeeding.
• Currently enrolled in an intervention study.

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• Research Foundation Flanders: collaborator
• KU Leuven: collaborator
• Vrije Universiteit Brussel: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (3)

UPC Duffel

Duffel, Antwerpen, 2570, Belgium

RECRUITING

UZ Brussel

Brussels, Belgium

RECRUITING

Katholiek Universiteit Leuven Campus Kortenberg

Leuven, Belgium

RECRUITING

Related Publications (4)

• 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 BACKGROUND

• Foley EM, Parkinson JT, Kappelmann N, Khandaker GM. Clinical phenotypes of depressed patients with evidence of inflammation and somatic symptoms. Compr Psychoneuroendocrinol. 2021 Aug 5;8:100079. doi: 10.1016/j.cpnec.2021.100079. eCollection 2021 Nov.

  PMID: 34729541 BACKGROUND

• Carvalho LA, Torre JP, Papadopoulos AS, Poon L, Juruena MF, Markopoulou K, Cleare AJ, Pariante CM. Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. J Affect Disord. 2013 May 15;148(1):136-40. doi: 10.1016/j.jad.2012.10.036. Epub 2012 Nov 27.

  PMID: 23200297 BACKGROUND

• Wessa C, Janssens J, Coppens V, El Abdellati K, Vergaelen E, van den Ameele S, Baeken C, Zeeuws D, Milaneschi Y, Lamers F, Penninx B, Claes S, Morrens M, De Picker L. Efficacy of inflammation-based stratification for add-on celecoxib or minocycline in major depressive disorder: Protocol of the INSTA-MD double-blind placebo-controlled randomised clinical trial. Brain Behav Immun Health. 2024 Sep 19;41:100871. doi: 10.1016/j.bbih.2024.100871. eCollection 2024 Nov.

  PMID: 39350954 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation; cyclopia sequence

Interventions

Celecoxib; Minocycline

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; 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; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Manuel Morrens, MD PhD

  Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonas Janssens, MD

CONTACT

015304643; jonas.janssens@emmaus.be

Celine Wessa, MD

CONTACT

Celine.wessa@emmaus.be

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: Professor Doctor

Study Record Dates

• First Submitted: November 24, 2022
• First Posted: December 9, 2022
• Study Start: September 21, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3)