Minocycline Augmentation in Schizophrenia

Minocycline Augmentation in Early-Course Schizophrenia

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.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Minocycline; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77021
      • Recruiting
      • Harris County Psychiatric Center
      • Contact: Nina Herring, RN, BSN; Phone Number: 713-741-4820; Email: Nina.G.Herring@uth.tmc.edu
      • Sub-Investigator: Adel Wasseff, M.D.
      • Principal Investigator: Mujeeb U Shad, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; EquivalentPlacebo will be given
Experimental: Minocycline	Drug: Minocycline; Minocycline will be given orally at 200 mg a day for 4 months; Other Names: Minocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)	PANSS total score will be used to examine treatment-induced change in psychaopthology. The PANSS is a 30-item rating scale used to assess symptoms of psychopathology. We will use the total PANSS score as the primary outcome measure which reflects total level of psychopathology including the positive and negative symptoms as well as general psychopathology.This measure will be administered at baseline, week 8 and week 16 of the study to assess if minocyline treatment results in a significant reduction in PANSS total score as opposed to placebo.	Baseline, week 8, and week 16 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-induced change in MATRICS Cognitive Consensus Battery (MCCB)	Average total score on MCCB will be used to examine treatment-induced change in cognitive function. MCCB (Nuechterlein et al., 2008) will be admisnitered at the baseline an week 16 of the study. The MCCB assesses 7 domains of cognitive functioning known to be impaired for individuals with schizophrenia. A summary score averaging across domains is generated as a global measure of cognitive functioning.	Baseline and week 16 of the study
Treatment-induced changes in plasma level of cytokines	Cytokine levels will assessed at baseline and week 16 of the study to examine treatment-induced changes in neuroinflammation.	Baseline and week 16 of the study

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Stanley Medical Research Institute
• Investigators: Principal Investigator: Mujeeb U Shad, MD, MSCS, UT Health Sciences Center at Houston

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Anticipated): January 1, 2015
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): March 23, 2012
• Last Update Submitted That Met QC Criteria: March 22, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: minocycline, augmentation, schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: HSC-MS-11-0201