E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Psychosis spectrum disorders, i.e. schizophrenia, psychotic disorders, schizoaffective disorders, etc. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study will investigate the effectiveness of a combination of anti-inflammatory agents, i.e. minocycline and celecoxib, as add-on to antipsychotics. Previous research has shown a success in alleviating symptom severity, however, the efficacy of the combination of minocycline and celecoxib has never been assessed in psychosis. Primary objective : Validate the efficacy of the combination treatment of minocycline and celecoxib in patients with psychotic illness.
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E.2.2 | Secondary objectives of the trial |
Evaluate the use of immune-based biomarkers as a predictor for treatment response; identify (an) immunophenotype(s) of psychosis
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Male or female, 18-55 years inclusive ● Able and willing to give informed consent ● Physically healthy ● If female and premenopausal: must agree to use adequate hormonal contraceptive protection method for the entire duration of the study ● Fulfill DSM-5 criteria for the schizophrenia spectrum (DSM-5 #295.1–295.6, 295.9,298.9) ● A minimum of two previous documented psychotic episodes ● Current residual psychotic symptoms, defined as a score of ≥ 4 on at least two PANSS positive subscale items, or a score of ≥ 6 on one positive subscale item ● Stably treated with antipsychotics for 4 weeks
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E.4 | Principal exclusion criteria |
● Pregnancy or breastfeeding ● Currently enrolled in an intervention study ● Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.) ● Alcohol and/or substance use disorders according to DSM-5 (< 4 weeks before screening, excl. nicotine and caffeine) ● History of peptic ulcer disease or gastrointestinal (GI) bleeding ● Inflammatory bowel disease ● Cardiovascular disease, thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery) ● Liver impairment (serum albumin < 25 g/L or Child-Pugh score ≥ 10) ● Renal impairment (creatinine clearance < 30 mL/min) ● NSAID and/or tetracycline and/or sulphonamide hypersensitivity ● Leukocytosis (i.e., white blood cell count > 11 x10^9 /L) on screening and test days. ● Chronic severe hypertension (systolic BP > 170 mmHg on 2 measurements) ● Serology positive for hep-B surface antigen, hep-C antibodies or HIV antibodies ● Received ECT < 2 months prior to screening ● Blood donation in 30 days prior to screening
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E.5 End points |
E.5.1 | Primary end point(s) |
Improvement of psychosis and psychosis-related symptoms (i.e. negative symptoms, cognitive symptoms), measured via the change in total PANSS score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All evaluation points: T0 (screening), T1 (start treatment), T2 (week 4 of treatment), T3 (week 8 of treatment), and T4 (end of treatment) |
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E.5.2 | Secondary end point(s) |
- change in severity of psychotic symptoms as measured by the positive symptoms subscale of the PANSS - change in severity of negative symptoms as measured by the negative symptoms subscale of the PANSS, - change in severity of depression measured as change in the CDSS score, - change in severity of cognitive symptomatology measured as change in cognitive test performance, - difference in clinically prescribed cumulative doses of antipsychotic medication over the intervention period - medication adherence and - adverse effects.
Tertiary outcome measure comprises of biomarker outcomes and will be measured via e.g. cytokine concentrations, oxidative stress and metabolic markers and tryptophan catabolites. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All except cognitive outcome measure at all evaluation points: T0 (screening), T1 (start treatment), T2 (week 4 of treatment), T3 (week 8 of treatment), and T4 (end of treatment)
cognitive outcome measure will be assessed at T1, T2 and T4. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
rater-blind, patients will know which drug they received |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (end of treatment or in case of dropout) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |