Clinical trial NCT02533232: Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia
Official title: Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Keywords: Schizophrenia
Anti-inflammatory
Clozapine
Minocycline
Psychosis NOS
Lead sponsor: Pakistan Institute of Living and Learning
Sponsor class: OTHER
First posted: 2015-08-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This a randomized double-blind placebo controlled trial which aims to determine the beneficial effects of minocycline augmentation to clozapine in partial responders to Treatment Resistant Schizophrenia (TRS).

Detailed description: The primary objective is to determine if the addition of minocycline to Clozapine, Treatment as Usual (TAU) Improves negative symptoms and/or positive symptoms.

The secondary objectives are to determine:

* Effects on cognitive functioning.
* Effects on social functioning and quality of life.
* Safety and tolerability.
* Possible additive effects of Minocycline added to TAU
* The effect on inflammatory biomarkers associated with schizophrenia. Both pro and anti-inflammatory cytokines will be drawn at baseline and endpoint. We will test to see if minocycline is associated with improvements in abnormal cytokines as compared to placebo.

The study will be a randomized double-blind placebo controlled trial of minocycline added to clozapine (Treatment as Usual) in TRS. There will be two treatment arms: one arm receiving TAU with minocycline and the other TAU with placebo for a period of twelve weeks.

Eligibility criteria: Inclusion Criteria:

* Male and female patients aged between 18-65 years, IQ \>70 (to complete assessments) identified by treating psychiatrist.
* Confirmation of schizophrenia by using The MINI psychiatric interview (at baseline only)
* Assessed as competent to provide informed consent by treating psychiatrist.
* Antipsychotic medication has remained stable 4 weeks prior to baseline \*. Assessed as a partial responder to clozapine: patients prescribed clozapine at a stable therapeutic dose for a minimum of 3 months with total Positive and Negative Syndrome Schizophrenia (PANSS) score \>70.

Exclusion Criteria:

* Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the Tetracyclines.
* Concomitant Penicillin therapy or concomitant anticoagulant therapy.
* Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to ICD 10 criteria.
* Treatment with Warfarin or Lamotrigine.
* Current or previous treatment with minocycline or other tetracycline antibiotics in the preceding three months before study entry.
* Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the principal investigator may interfere with the study.
* Pregnant or breast-feeding females

Primary outcomes:
measure: Positive and Negative Syndrome Scale PANSS
timeFrame: 3 months
Secondary outcomes:
measure: CogState
timeFrame: 3 Month
Other outcomes:
measure: Social Functioning Scale
timeFrame: 3 Month
Locations:
city: Karachi
country: Pakistan
facility: Abasi Shaheed Hospital
state: Sindh
city: Karachi
country: Pakistan
facility: Civil hospital Karachi
state: Sindh
city: Karachi
country: Pakistan
facility: Karwn e Hayat
state: Sindh
city: Karachi
country: Pakistan
facility: Institute of Behavioral Sciences
state: Sindh
Study officials:
affiliation: Manchester University ,UK
name: Dr.Inti Qurashi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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