The Benefit of Minocycline on Negative Symptoms in Schizophrenia: Extent and Mechanisms

NCT02928965 | Completed Phase 2 DMC

• 3 other identifiers: EME-09/100/232010-022463-3510411
• Study Type: interventional
• Target: 207
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Schizophrenia and Disorders With Psychotic Features

Keywords

psychosis; schizophrenia; negative symptoms; minocycline

Outcome Measures

Primary Outcomes (1)

• Severity of negative symptoms of psychosis

  Measured by Negative symptoms scale in the Positive and Negative Syndrome Scale

  twelve months

Secondary Outcomes (7)

• Change in body weight

  Twelve months

• Positive symptoms of psychosis

  twelve months

• General social and psychological functioning

  twelve months

• Intelligence

  twelve months

• Anti-psychotic medication dose

  twelve months

Other Outcomes (8)

• Change in medial prefrontal grey matter volume (primary biomarker outcome)

  twelve months

• Circulating interleukin (IL-6) concentration (primary biomarker outcome)

  twelve months

• Dorsolateral-prefrontal cortex blood oxygen level dependent response during working memory task (primary biomarker outcome)

  twelve months

Study Arms (2)

Minocycline

EXPERIMENTAL

Participants will receive capsules containing 100mg of minocycline (modified release), two per day for the first two weeks of the trial and then three per day for the remainder of the 12 month treatment period in addition to antipsychotic drug treatment and other interventions by the responsibel medical officer.

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

Participants will receive placebo capsules entirely matching minocycline, two per day for the first two weeks of the trial and then three per day for the reminder of the 12 month treatment period in addition to antipsychotic drug treatment and other interventions by the responsibel medical officer.

Drug: Placebo

Interventions

Minocycline DRUG

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.

Also known as: Acnamino MR (modified release)

Minocycline

Placebo DRUG

Matching placebo with appearance of over - encapsulated minocycline

Placebo

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Meeting DSM-IV criteria for schizophrenia, schizophreniform or schizo-affective psychosis as assessed by the research team
• In an episode as defined by the presence of positive symptoms measured by Positive and Negative Syndrome Scale with a score higher than two in items 1,2,3 or 6 in the Positive scale
• In contact with early intervention community or in-patient service
• Within 5 years of first diagnosis
• Intelligence quotient (IQ) greater than 70
• Participants and their partners must be willing to use effective birth control throughout the study and seven days after stopping trial medication. Females should have a negative pregnancy test
• Able to understand and willing to give written informed consent
• Fluent in English

You may not qualify if:

• Current substance misuse diagnosis that in the opinion of the investigator may interfere with the study
• Patients who, in the investigator's judgement pose a current serious suicidal or violence risk
• Use of tetracycline antibiotics within 2 months of the randomisation visit or history of sensitivity or intolerance for this type of antibiotics
• History of Systemic Lupus Erythematosis (SLE) or a history of SLE in a first-degree relative
• Use of any investigational drug within a month of randomisation visit
• Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder in the opinion of the principal investigator (PI) or the responsible medical officer (RMO) may interfere with the trial
• Taking medical treatments that could seriously interact with minocycline as described in the summary of product characteristics (SPC) and judged by the PI or the RMO
• Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
• Previous randomisation in the present study
• Pregnant or breastfeeding

Sponsors & Collaborators

• University of Manchester: lead
• University of Edinburgh: collaborator
• University of Cambridge: collaborator
• University College, London: collaborator
• University of Birmingham: collaborator
• King's College London: collaborator
• Manchester Mental Health & Social Care Trust: collaborator
• Greater Manchester Mental Health NHS Foundation Trust: collaborator
• Northern Care Alliance NHS Foundation Trust: collaborator
• Lancashire Care NHS Foundation Trust: collaborator
• Cambridgeshire and Peterborough NHS Foundation Trust: collaborator
• West London Mental Health NHS Trust: collaborator
• North East London Foundation Trust: collaborator
• Central and North West London NHS Foundation Trust: collaborator
• Camden and Islington NHS Foundation Trust: collaborator
• South London and Maudsley NHS Foundation Trust: collaborator
• NHS Lothian: collaborator
• NHS Fife: collaborator
• NHS Borders: collaborator
• University Hospital Birmingham NHS Foundation Trust: collaborator

MeSH Terms

Conditions

Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Schizophrenia; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Bill Deakin, Professor

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Director of Neuroscience Research in the Division of Psychiatry

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: October 10, 2016
• Study Start: February 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: April 18, 2019

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: January 2019
• Access Criteria: Academic researcher, clear analysis plan, publication plan Agreement of Chief investigator