The Benefit of Minocycline on Negative Symptoms in Schizophrenia: Extent and Mechanisms
Condition: Schizophrenia and Disorders With Psychotic Features
MeSH terms: Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to investigate if minocycline limits the development of negative
      symptoms in early psychosis and to test via what mechanism of action this change occurs.
    

Detailed description: 
      Background

      Negative symptoms of psychosis do not respond to the traditional therapy with first- or
      second-generation antipsychotics and are among main causes of a decrease in quality of life
      observed in individuals suffering from the disorder. Minocycline, a broad-spectrum
      tetracyclic antibiotic displaying neuroprotective properties has been suggested as a new
      potential therapy for negative symptoms. In the two previous clinical trials comparing
      minocycline and placebo, both added to the standard care, patients receiving minocycline
      showed increased reduction in negative symptoms. Three routes to neuroprotection by
      minocycline have been identified: neuroprotection against grey matter loss, anti-inflammatory
      action and stabilisation of glutamate receptors. However, it is not yet certain what the
      extent of the benefit of minocycline in psychosis is and what its mechanism is. This proposal
      is for a multi-centre double-blind randomised placebo-controlled clinical trial entitled The
      Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin).

      Methods

      After providing informed consent, 226 participants in the early phase of psychosis will be
      randomised to receive either 100 mg modified-release capsules of minocycline or similar
      capsules with placebo for 12 months in addition to standard care. The participants will be
      tested for outcome variables before and after the intervention period. The extent of benefit
      will be tested via clinical outcome measures, namely the Positive and Negative Syndrome Scale
      score, social and cognitive functioning scores, antipsychotic medication dose equivalent and
      level of weight gain. The mechanism of action of minocycline will be tested via blood
      screening for circulating cytokines and magnetic resonance imaging with three-dimensional
      T1-weighted rapid gradient-echo, proton density T2-weighted dual echo and T2*-weighted
      gradient echo planar imaging with N-back task and resting state. Eight research centres in
      the United Kingdom (UK) and 15 National Health Service Trusts and Health Boards will be
      involved in recruiting participants, performing the study and analysing the data.
    

Intervention name(s): Minocycline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Capsules containing 100mg minocycline (modified release), administered orally by the patient, two per day for the first two weeks and then three per day for the reminder of the 12 month treatment period in addition to standard therapy.; Matching placebo with appearance of over - encapsulated minocycline
Other intervention name(s): Acnamino MR (modified release)
Intervention MeSH terms: Minocycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: psychosis; schizophrenia; negative symptoms; minocycline