INflammation-based Stratification for Immune-Targeted Augmentation in Major Depressive Disorder (INSTA-MD)

October 9, 2024 updated by: Manuel Morrens, Universiteit Antwerpen

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This project aims to repurpose two established anti-inflammatory compounds as adjuvant therapy for immune-mediated depression, in line with state-of-the-art research of the last 10 years. Immune-mediated depression represents a subtype which accounts for approximately 30% of depressive disorders. Patients with this immunosubtype are more likely to have a higher severity of depression, a lower quality of life and more somatic symptoms. Furthermore it is accompanied by a high incidence of treatment resistance. While their mechanisms of action completely differ from those of existing antidepressant treatment options, immunomodulatory drugs celecoxib and minocycline have proven their merit as add-on treatment in depressive episodes. They have been on the Belgian market for years and come with a known pharmacological and safety profile. Patient stratification at baseline based on inflammatory status will reveal which inflammatory subpopulation benefits most from each of the two investigated anti-inflammatory compounds. Additionally, our distinctive study design allows head-to-head comparison of both add-on therapies and will as such provide the last stepping stones towards clinical implementation of individualised treatment strategies in depression.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
240

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Belgium
      • Brussels, Belgium
        • Recruiting
        • UZ Brussel
        • Contact:
          • Chris Baeken, PhD MD
      • Leuven, Belgium
        • Recruiting
        • Katholiek Universiteit Leuven Campus Kortenberg
        • Contact:
          • Elfi Vergaelen, MD PhD
        • Sub-Investigator:
          • Emma Saillart
    • Antwerpen
      • Duffel, Antwerpen, Belgium, 2570
        • Recruiting
        • UPC Duffel
        • Contact:
        • Sub-Investigator:
          • Tim Rietberg
        • Sub-Investigator:
          • Céline Wessa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Minocyclin + Treatment As Usual (TAU)
Drug: Minocyclin
Oral capsule, 100 mg, twice daily, for 12 weeks
Active Comparator: High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Celecoxib + Treatment As Usual (TAU)
Drug: Celecoxib
Oral capsule, 200 mg, twice daily, for 12 weeks
Placebo Comparator: High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Placebo + Treatment As Usual (TAU)
Drug: Placebo
Oral capsule, no active substance, twice daily, for 12 weeks
Active Comparator: High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Minocyclin + Treatment As Usual (TAU)
Drug: Minocyclin
Oral capsule, 100 mg, twice daily, for 12 weeks
Active Comparator: High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Celecoxib + Treatment As Usual (TAU)
Drug: Celecoxib
Oral capsule, 200 mg, twice daily, for 12 weeks
Placebo Comparator: High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Placebo + Treatment As Usual (TAU)
Drug: Placebo
Oral capsule, no active substance, twice daily, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in depressive symptom severity (HDRS-17)
Time Frame: T0 -> T6 (12 weeks)
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)
Time Frame: T0 -> T6 (12 weeks)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in depressive symptom severity (IDS-30SR)
Time Frame: T0 -> T6 (12 weeks)
Change in severity of depression measured as the change in the Inventory of Depressive Symptomatology - Self Report (IDS-SR; score is ranging from 0 to 84, higher scores indicate higher severity of depressive symptoms)
T0 -> T6 (12 weeks)
Response rate of depressive symptoms (HDRS-17)
Time Frame: T0 -> T6 (12 weeks)
Response rates of the depressive symptoms measured 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), with response being defined as a 50% reduction in HDRS-17-score from baseline and partial response as a 25% reduction.
T0 -> T6 (12 weeks)
Change in night-time sleep (PSQI)
Time Frame: T0 -> T6 (12 weeks)
Change in night-time sleep quality and/or quantity measured on the Pittsburgh Sleep Quality Index (PSQI; score is ranging from 0 to 21, higher scores indicate more sleep disturbances)
T0 -> T6 (12 weeks)
Change in anxiety (STAI)
Time Frame: T0 -> T6 (12 weeks)
Change in anxiety measured on the Stait Trait Anxiety Inventory-Self Report (STAI; score is ranging from 20 tot 80, higher scores indicate higher levels of anxiety intensity)
T0 -> T6 (12 weeks)
Change in core assessment of psychomotor change (CORE)
Time Frame: T0 -> T6 (12 weeks)
Change in the degree of psychomotor disturbance (which is as an integral component of melancholia) measured on the Core Assessment Of Psychomotor Change (CORE; score is ranging from 0-54, higher scores indicate higher levels of psychomotor disturbances)
T0 -> T6 (12 weeks)
Depressive symptom profiles (IDS-SR)
Time Frame: T0 -> T6 (12 weeks)
Profile of the depression measured on the Inventory of Depressive Symptomatology - Self Report (IDS-SR; score is ranging from 0 to 84, higher scores indicate higher severity of depressive symptoms)
T0 -> T6 (12 weeks)
Therapy compliance (MARS)
Time Frame: T0 -> T6 (12 weeks)
Therapy compliance measured on the Medication Adherence Scale (MARS; score is ranging from 0-10, higher scores indicate better medication adherence)
T0 -> T6 (12 weeks)
Adverse effects
Time Frame: T0 -> T6 (12 weeks)
Side effects measured with a questionnaire based on the list as used in the Antidepressant Side-Effect Checklist (ASEC-21) and the known side effects of Minocycline and Celecoxib
T0 -> T6 (12 weeks)
Metabolic blood markers
Time Frame: T0 -> T6 (12 weeks)
Cholesterol (mg/dl), High Density Lipoprotein (HDL) (mg/dl), Low Density Lipoprotein (LDL) (mg/dl), fasting glucose (mg/dl), triglycerides (mg/dl)
T0 -> T6 (12 weeks)
Other metabolic measures
Time Frame: T0 -> T6 (12 weeks)
Waist circumference (cm), height (cm) will be measured to calculate the BMI (kg/m^2)
T0 -> T6 (12 weeks)
Other metabolic measures
Time Frame: T0 -> T6 (12 weeks)
Weight (kg) will be measured to calculate the BMI (kg/m^2)
T0 -> T6 (12 weeks)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Immune markers
Time Frame: T0 -> T6 (12 weeks)
Cytokines: interleukin-6, interleukin-1β, tumor necrosis factor α, interferon γ, Interleukin-1 receptor, interleukin-7
T0 -> T6 (12 weeks)
Alternate immune markers
Time Frame: T0 -> T6 (12 weeks)
Peripheral blood monocytes (PBMCs)
T0 -> T6 (12 weeks)
Tryptophan pathway metabolites
Time Frame: T0 -> T6 (12 weeks)
Kynurenine (KYN), Kynurenic Acid (KYNA), Quinolinic Acid (QA), 3-Hydroxykynurenine (3-HK)
T0 -> T6 (12 weeks)
Vascular and (neuro)trophic factors
Time Frame: T0 -> T6 (12 weeks)
Vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF)
T0 -> T6 (12 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universiteit Antwerpen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
KU Leuven
Amsterdam UMC, location VUmc
Vrije Universiteit Brussel
Research Foundation Flanders

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Manuel Morrens, MD PhD, Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • T001222N

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

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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