Recipient organisationUniversity of ManchesterSource-published name: The University of Manchester
Funding£1.9M
PeriodJul 2011 — Sept 2016
In plain English
AI plain-English summary
A common antibiotic, minocycline, is being tested on 170 patients with early psychosis to see if it can prevent or reduce the negative symptoms of schizophrenia—such as social withdrawal and lack of motivation—that standard antipsychotics often fail to treat. These negative symptoms are a major unmet need in schizophrenia care. They persist after positive symptoms like hallucinations are controlled, and they severely undermine quality of life, employment, and relationships. Current drugs do little for them, and no established treatment exists. This trial is the first to rigorously test whether minocycline, an anti-inflammatory drug with effects on brain cell loss and glutamate signalling, can fill that gap. If minocycline works, it would offer a cheap, safe, add-on therapy that could be started early in the illness to prevent long-term disability. The trial also collects brain scans, blood markers of inflammation, and cognitive tests to reveal *how* the drug works—whether by preserving grey matter, dampening immune signals, or improving brain chemistry. Even if minocycline fails, the mechanistic data will clarify which biological pathways drive negative symptoms, guiding future drug development. The results could reshape early intervention protocols in psychosis services across the NHS.
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AIMS: to use recently developed PsyGrid infrastructure for UK-wide clinical and imaging research in first episode psychosis to: i) determine whether negative symptoms can be lessened or prevented by minocycline treatment initiated early in the course of schizophrenia and ii) collect biomarker data to test hypotheses about how minocycline improves negative symptoms. PRIMARY EFFICACY PREDICTION AND MECHANISTIC HYPOTHESES: 1) Minocycline minimises later negative symptoms when administered during the acute phase of early psychosis 2) Minocycline reduces or prevents the negative symptoms of schizophrenia by: a) reducing the loss of grey matter associated with early psychosis. b) interfering with inflammatory cytokine production. c) an action on glutamate systems to improve negative symptoms and cognitive function. DESIGN. Multicentre, one year, double-blind randomised placebo-controlled trial of minocycline versus placebo, added to standard antipsychotic drug (APD) treatment, for patients in an early episode of schizophrenia-related psychosis. INTERVENTION. Minocycline or matching placebo 300mg daily for 12 months. OUTCOMES. The primary clinical outcome is negative symdrome subscale score on the Positive and Negative Syndrome Scale (PANSS). The mechanistic biomarker variables are: 1) change in medial prefrontal grey matter volume over 12 months, 2) circulating cytokine concentrations and 3) working memory performance and brain activation. These measures will be related to changes in PANSS negative symptoms at 2, and 12 months and to quality of life assessments. POPULATION AND SAMPLE SIZE. 170 patients with early psychosis recruited over 22 months from 6 established PsyGrid centres. STATISTICAL ANALYSIS. Group differences in outcomes and putative mediators will be evaluated using random effects models for longitudinal data (allowing for treatment centre and other baseline covariates). Tests of the mechanistic hypotheses (i.e. mediation), and their sensitivity of the results to possible hidden confounding, will use instrumental variable methods from PI Dunn’s MRC Methodology Research Programme projects; see Emsley R, Dunn G & White I (2009) modelling mediation and moderation of treatment effects in randomised controlled trials of complex interventions. Statistical Methods in Medical Research published online on 16/07/09. EXPERTISE. The investigators are experienced in the recruitment of early psychosis patients and the confidential collection of clinical assessments and brain imaging through their involvement in PsyGrid and NeuroPsyGrid.
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