Schizophrenia and Disorders With Psychotic FeaturesPhase 2BeneMinNCT02928965
The Benefit of Minocycline on Negative Symptoms in Schizophrenia: Extent and Mechanisms
A Phase 2 study testing Minocycline in people with Schizophrenia and Disorders With Psychotic Features, run by University of Manchester.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 35 years
- Conditions the study is for
- Schizophrenia and Disorders With Psychotic Features
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 207 participants
- Where
- No sites listed yet
- Study dates
- Feb 2013to May 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
- Meeting MRI exclusion criteria as defined by local scanning centres
About this study
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.
Read the 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.
- Being tested
- Minocycline, Placebo
- Keywords
- psychosis, schizophrenia, negative symptoms, minocycline
- Medical subject headings
- Schizophrenia Spectrum and Other Psychotic Disorders, Psychotic Disorders, Schizophrenia, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Acnamino MR (modified release)
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.
PlaceboDrug
Matching placebo with appearance of over - encapsulated minocycline
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of negative symptoms of psychosis
Measured by Negative symptoms scale in the Positive and Negative Syndrome Scale
Measured: twelve months
Secondary outcomes (7)
Change in body weight
Measuring weight gain in kilograms, a side effect of standard anti-psychotic medication therapy
Measured: Twelve months
Positive symptoms of psychosis
Measured by the Positive symptoms scale in the Positive and Negative Syndrome Scales
Measured: twelve months
General social and psychological functioning
Measured by Global Assessment of Functioning from DSM-IV
Measured: twelve months
Intelligence
Measured by Wechsler Adult Intelligence Scale for patients with schizophrenia
Measured: twelve months
Anti-psychotic medication dose
Measured in chlorpromazine equivalent units
Measured: twelve months
Verbal learning
Auditory-Verbal Learning Task
Measured: 12 months
Social and Occupational functioning
Score on Social Functioning Scale
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2016 (estimated)
- Study startFeb 2013
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia and Disorders With Psychotic FeaturesStudies of the same condition, open and under way.
- More trials run by University of ManchesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Collaborators
- University of Edinburgh, University of Cambridge, University College, London, University of Birmingham, King's College London, Manchester Mental Health & Social Care Trust, Greater Manchester Mental Health NHS Foundation Trust, Northern Care Alliance NHS Foundation Trust, Lancashire Care NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust, West London Mental Health NHS Trust, North East London Foundation Trust, Central and North West London NHS Foundation Trust, Camden and Islington NHS Foundation Trust, South London and Maudsley NHS Foundation Trust, NHS Lothian, NHS Fife, NHS Borders, University Hospital Birmingham NHS Foundation Trust
- Responsible party
- Principal investigator, Bill Deakin, University of Manchester
- Investigators
- Bill Deakin, Professor, Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02928965
- Sponsor's protocol ID
- EME-09/100/23
- Other IDs
- 2010-022463-35, 10411
- Acronym
- BeneMin
- Status last verified
- Oct 2017
- First submitted
- 23 Sep 2016
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Fully anonymised database will be made available in 2018. Basic demographics, Primary clinical and mechanistic outcome measures. Treatment allocation code
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Benefit of Minocycline on Negative Symptoms in Schizophrenia: Extent and Mechanisms
- ClinicalTrials.gov ID
- NCT02928965
- Acronym / sponsor ID
- BeneMin / EME-09/100/23
- Keywords
- psychosis, schizophrenia, negative symptoms, minocycline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Collaborators
- University of Edinburgh, University of Cambridge, University College, London, University of Birmingham, King's College London, Manchester Mental Health & Social Care Trust, Greater Manchester Mental Health NHS Foundation Trust, Northern Care Alliance NHS Foundation Trust, Lancashire Care NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust, West London Mental Health NHS Trust, North East London Foundation Trust, Central and North West London NHS Foundation Trust, Camden and Islington NHS Foundation Trust, South London and Maudsley NHS Foundation Trust, NHS Lothian, NHS Fife, NHS Borders, University Hospital Birmingham NHS Foundation Trust
- Study start
- Feb 2013
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 10 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Experimental | Drug: MinocyclineParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 16 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: Acnamino MR (modified release)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. | Drug | Minocycline |
| PlaceboMatching placebo with appearance of over - encapsulated minocycline | Drug | Placebo |
Primary outcome
Severity of negative symptoms of psychosis
Time frame: twelve months
Measured by Negative symptoms scale in the Positive and Negative Syndrome Scale
7 secondary outcomes
Change in body weight
Time frame: Twelve months
Positive symptoms of psychosis
Time frame: twelve months
General social and psychological functioning
Time frame: twelve months
Intelligence
Time frame: twelve months
Anti-psychotic medication dose
Time frame: twelve months
Verbal learning
Time frame: 12 months
Social and Occupational functioning
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Individual participant dataSharing planned: Yes. Fully anonymised database will be made available in 2018. Basic demographics, Primary clinical and mechanistic outcome measures. Treatment allocation code
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bill Deakin, Professor principal investigator
University of Manchester
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Minocycline in people with Schizophrenia and Disorders With Psychotic Features, run by University of Manchester.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of negative symptoms of psychosis (time frame: twelve months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.