E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
To confirm that minocycline benefits the negative symptoms of schizophrenia when taken early in the course of the illness and to understand how it does so. To determine whether minocycline acts by protecting brain cells from damage, by lessening inflammation or by improving mental functions (thinking and reasoning). |
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E.2.2 | Secondary objectives of the trial |
1- Does minocycline reduce weight gain induced changes by standard antipsychotic treatments (APD)? 2- Do improvements in negative symptoms translate into improved social and occupational functioning and quality of life (QoL)? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female aged 16-35 years 2) Current DSMIV diagnosis of schizophrenia, schizophreniform or schizo-affective psychosis, psychosis NOS as assessed with the clinical team. 3) In an episode as defined by a) an onset or exacerbation of symptoms and b) with continuing positive symptoms scoring at least mild (>2) on items P1,P2 or P6 of the PANSS within the last month 4) In contact with early intervention, community or in-patient services, 5) Within 3 years of onset of symptoms 6) Current IQ greater than 70 7) Female patients must use effective birth control with a negative pregnancy test 8) Able to understand and willing to give written informed consent 9) Fluent in English |
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E.4 | Principal exclusion criteria |
1) Current substance misuse diagnosis that in the opinion of the investigator may interfere with the study. Urine toxicology screens will be used to monitor drug use. 2) Patients who, in the Investigator’s judgment pose a current serious suicidal or violence risk 3) Prior tetracycline use within 2 months of baseline visit or history of sensitivity or intolerance 4) History of systemic lupus erythematosis (SLE) or a history of SLE in a first-degree relative 5) Use of any investigational drug within 30 days of baseline visit 6) Relevant current or past haematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the investigator may interfere with the study 7) Clinically significant deviation from the reference range in clinical laboratory test results as judged by the Investigator. 8) Previous randomisation in the present study. 9) Pregnant or nursing. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy outcome variable: Negative symptom severity at 12 months as defined by negative factor subscale score on the PANSS. This is the gold standard scale for comprehensively rating symptoms of schizophrenia. The negative symptom factor subscale is composed of 7 items each rated 1-7. Primary mechanistic biomarker outcome variables: 1) Medial prefrontal grey matter volume, 2) Circulating cytokine IL-6 concentration, 3) Dorsolateral prefrontal cortex blood oxygen level dependent (BOLD) response, % correct and connectivity during the N-back task, |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Mechanistic study to understand how the drug works |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
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 | Yes |
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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When the last patient has completed the 3 month follow-up assessments. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 29 |