INSTA-MD: INflammation-based Stratification for immune-Targeted Augmentation in Major Depressive disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Antwerp

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

21 Sep 2023 → ongoing

Decision date (initial)

2023-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

FWO Fonds Wetenschappelijk Onderzoek

External identifiers

EU CT number

2022-501692-35-00

ClinicalTrials.gov

NCT05644301

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Validate the efficacy of immune-targeted augmentation with minocycline or celecoxib in a Flemish cohort of patients with MDD who failed to remit with one or two trials of antidepressant treatment

Secondary objectives 3

1. Compare the respective acceptability, treatment response and remission rates of minocycline and celecoxib as adjunctive therapy
2. Compare the efficacy of both compounds as adjunctive therapy in an immune-mediated subtype of MDD versus an unstratified patient sample
3. Evaluate the use of hsCRP as a predictor for treatment response to minocycline and celecoxib.

Conditions and MedDRA coding

Major Depressive Disorder (MDD)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female, 18-65 years inclusive
2. Able and willing to give informed consent and take oral medication
3. Physically healthy
4. Diagnosis of Major Depressive Disorder by DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI)
5. 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
6. Tolerant to the current antidepressant and having no planned changes in their current therapy for the duration of the study.
7. Stable on current treatment for a minimum of 4 weeks (6 weeks for fluoxetine) prior to baseline.
8. If female and of childbearing age, willing to use adequate contraceptive precautions and willing to take pregnancy tests.
9. A score of 14 or higher on the Hamilton Depression Rating scale (HDRS-17)

Exclusion criteria 17

1. Primary diagnosis of bipolar disorder, psychotic spectrum disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or alcohol and/or substance use dependence according to DSM-5 (< 4 weeks before screening, excl. nicotine and caffeine)
2. Currently enrolled in an intervention study
3. Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.)
4. History of peptic ulcer disease or gastrointestinal (GI) bleeding
5. Having an acute infection or having an inflammatory bowel disorder.
6. Current severe cardiovascular disease (e.g. congestive heart failure (NYHA-class II–IV), ischemic or thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery))
7. Use of (Vitamin K) anticoagulant therapy
8. Having received >14 days of tetracycline or NSAID within the previous 2 months, or having a history of sensitivity or intolerance to this classes of drugs
9. Chronic severe hypertension (systolic BP > 170 mmHg)
10. Serology positive for hep-B surface antigen, hep-C antibodies or HIV antibodies
11. Received ECT < 2 months prior to screening
12. The current episode of depression has failed to remit after three trials of antidepressant treatment.
13. Blood donation in 30 days prior to screening
14. Concomitant penicillin or anticoagulant therapy
15. Pregnancy or breastfeeding
16. Being diagnosed with Familial Adenomatous Polyposis (FAP).
17. Having an acute infection in the last two weeks, neutrophilia or leukocytosis at screening (i.e. neutrophils ≥ 10 x10^9 /L or white blood cell count ≥ 12 x10^9 /L)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in severity of depression measured as change in the HDRS-17 between baseline and endpoint
2. Rates of remission (HDRS≤7) at endpoint

Secondary endpoints 10

1. Change in severity (IDS-30SR) Change in severity of depression measured as change in the IDS-30SR score [Time Frame: T0 -> T6 (12 weeks)]
2. Response rate (HDRS-17) Rates of response (50% reduction in HDRS score from baseline) or partial response (25% reduction) at endpoint [Time Frame: T0 -> T6 (12 weeks)]
3. Sleep (PSQI) [Time Frame: T0 -> T6 (12 weeks)]
4. Anxiety (STAI) [Time Frame: T0 -> T6 (12 weeks)]
5. Metabolic outcomes BMI, waist circumference, triglyceride, cholesterol, HDL and LDL levels, and fasting glucose [Time Frame: T0 -> T6 (12 weeks)]
6. Symptom profiles (IDS-SR) [Time Frame: T0 -> T6 (12 weeks)]
7. Therapy compliance (MARS) [Time Frame: T0 -> T6 (12 weeks)]
8. Adverse effects [Time Frame: T0 -> T6 (12 weeks)]
9. biomarker outcomes: cytokine concentrations, oxidative stress and metabolic markers
10. Core assessment of psychomotor change (CORE) [Time Frame: T0 -> T6 (12 weeks)]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Antwerp

Sponsor organisation

University Of Antwerp

Address

Universiteitsplein 1

City

Antwerp

Postcode

2610

Country

Belgium

Scientific contact point

Organisation

University Of Antwerp

Contact name

Manuel Morrens

Public contact point

Organisation

University Of Antwerp

Contact name

Manuel Morrens

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications