Clinical trial NCT01561742: Minocycline Augmentation in Schizophrenia
Official title: Minocycline Augmentation in Early-Course Schizophrenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schizophrenia
Keywords: minocycline, augmentation, schizophrenia
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2012-03-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to examine the efficacy of minocycline augmentation in a sample of moderately ill outpatients with early-course schizophrenia on their chlorpromazine-equivalent doses of second-generation antipsychotic medications. The investigators hypothesize that as compared to placebo a 2-month treatment with minocycline in 120 volunteers with early-course schizophrenia will result in a more significant improvement in psychopathology (primary outcome) and cognitive symptoms (secondary outcome). In addition, cytokine plasma levels will be used as another secondary outcome measure to see if treatment-induced changes in total PANSS score are associated with changes in cytokine levels.

Detailed description: Minocycline, which is a second-generation tetracycline, has been found to inhibit Nitric Oxide Synthase (NOS) and inflammatory cytokines. These are some of the primary mechanisms that have been proposed to explain its neuroprotective and neuroplastic effects in several animal and human models of neurological and psychiatric diseases, including Parkinson's disease and schizophrenia. There are only three clinical trials with minocycline in schizophrenia subjects. A more definitive clinical trial in a larger sample with optimized and cost-effective design using a comprehensive cognitive battery and a global assessment of schizophrenia symptom domains is necessary to examine the efficacy of minocycline. If minocycline improves psychopathology and potentially other symptoms (including cognitive function) for schizophrenia, the treatment could be easily implemented in the existing treatment delivery system at relatively low cost and have the potential for making a significant public health impact. The investigators plan to recruit 120 individuals with early course schizophrenia who are currently on second-generation antipsychotic (SGA) medications and are experiencing persistent symptoms in at least the moderate range. In an effort to limit placebo response, which is notoriously high in psychiatric population, the investigators are using an adaptive design. Since, there is growing evidence to support the inflammatory hypothesis of schizophrenia, the investigators will also explore whether cytokine levels mediate the response from minocycline treatment.

Eligibility criteria: Inclusion Criteria:

1. Ages between 18-35 years
2. Males \& females
3. Current DSM-IV diagnosis of schizophrenia or schizoaffective disorder confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.) conducted by a trained psychiatrist.
4. Treatment with a stable dose of second generation antipsychotic medication for at least 1 months prior to study entry 200-600 mg/day chlorpromazine equivalent doses);
5. Evidence of stable symptomatology for 12 weeks as evidenced by no hospitalizations for schizophrenia, no increase in level of psychiatric care due to worsening of symptoms, no ER use for symptoms of schizophrenia and no significant changes to antipsychotic medication or dose (\>25%) in the past 12 weeks.
6. Baseline total score between 40 and 65 on the Brief Psychiatric Rating Scale (BPRS);
7. Raw score of 12 or higher on the Wechsler Test of Adult Reading (WTAR) (estimates premorbid IQ).
8. Able to comprehend the procedure and aims of the study to provide informed consent

Exclusion Criteria:

1. Acute, unstable, significant or untreated medical illness beside schizophrenia;
2. Pregnant or breast-feeding females;
3. History of substance abuse or dependence in the past 3 months.
4. Known contraindication to minocycline treatment.
5. Treatment with minocycline or Beta-lactam antibiotics in the preceding half year before study entry.

Primary outcomes:
measure: Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)
timeFrame: Baseline, week 8, and week 16 of the study
Secondary outcomes:
measure: Treatment-induced change in MATRICS Cognitive Consensus Battery (MCCB)
timeFrame: Baseline and week 16 of the study
measure: Treatment-induced changes in plasma level of cytokines
timeFrame: Baseline and week 16 of the study
Other outcomes:
Locations:
city: Houston
country: United States
facility: Harris County Psychiatric Center
state: Texas
Study officials:
affiliation: UT Health Sciences Center at Houston
name: Mujeeb U Shad, MD, MSCS
role: PRINCIPAL_INVESTIGATOR
References: