Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
MPRC, University of Maryland
ClinicalTrials.gov Identifier:
NCT01433055
First received: July 21, 2011
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

Schizophrenia is a devastating and costly illness. One-third to one-half of people with schizophrenia do not respond to the most current drugs leaving clozapine as the best alternative for treatment. However, over 60% of people treated with clozapine continue to have persistent symptoms and cognitive impairments. Little data is available to support evidence-based recommendations to guide clinicians in treating these patients. Preliminary data has suggested that adjunct treatment with minocycline may offer robust symptom improvement in patients with schizophrenia, including those taking clozapine. Minocycline has had interesting effects; including suggesting it may have a significant role in treatment of neurologic and psychiatric disorders. Minocycline is currently available generically; its side effects are well-described and minimal. The proposed double-blind treatment study seeks to demonstrate that adjunctive minocycline offers patients superior efficacy for persistent positive symptoms, cognitive impairments, and/or other components of schizophrenia pathology. This knowledge could lead to the more effective treatment of patients with schizophrenia. The research itself may lead to a better understanding of the pathophysiology of positive symptoms and cognitive impairments, which could contribute to improved treatments in the future.


Condition Intervention
Schizophrenia
Drug: Minocycline
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • The efficacy of minocycline compared to placebo to improve positive Psychotic Symptoms [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    Adjunct minocycline to clozapine will be compared to placebo to test its efficacy to improve positive psychotic symptoms. The 4 item positive subfactor of the Brief Psychiatric Rating Scale (BPRS) will be the primary outcome over the 10 week randomized study.

  • The efficacy of minocycline compared to placebo to improve cognitive symptoms [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    Adjunct minocycline to clozapine will be compared to placebo to test its efficacy in improving cognitive function. Neuropsychological testing will be done at baseline and endpoint using the MATRICS battery. A composite score as well as individual scores will be will be the primary outcome over the 10 week randomized study.


Secondary Outcome Measures:
  • The efficacy of minocycline compared to placebo to improve negative symptoms. [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    Adjunct minocycline to clozapine will be compared to placebo to test its efficacy in improving negative symptoms of schizophrenia. The Scale for the Assessment of Negative Symptoms (SANS) will be used to test changes in the total SANS score in adjunct minocycline compared to placebo in the 10 week study.

  • The effect of minocycline on inflammatory biomarkers associated with schizophrenia. [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    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 safety of adjunct minocycline compared to placebo as defined by reported side effects, laboratory findings and extrapyramidal symptoms. [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    We will examine side effect reports by a standardized side effect checklist, various laboratory measures (hepatic, kidney, blood) and use the Simpson Angus Scale and Barnes Akathisia Scale to measure extrapyramidal side effects. We hypothesize that side effects rates will be similar to placebo. Additionally we will closely watch for skin pigmentation.

  • The efficacy of adjunct minocycline to placebo to improve depressive symptoms [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    The total score of the Calgary Depression Rating Scale will be used to examine the efficacy of minocycline compared to placebo in improving depressive symptoms.

  • The effect of adjunct minocycline to placebo on global clinical improvement of symptoms. [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    The Clinical Global Impression Severity score will be used to examine the effect of minocycline compared to placebo.

  • The efficacy of adjunct minocycline compared to placebo on perceived health quality and general well being. [ Time Frame: 10 Weeks ] [ Designated as safety issue: No ]
    We will use the Short Form 36 Health Survey and the Psychological General Well Being Schedule to measure changes. We hypothesize that minocycline will be superior to placebo.


Enrollment: 60
Study Start Date: July 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Minocycline Drug: Minocycline

Minocycline Dosing:

Minocycline (Dynacin® or generic) will be available in 50, 75 and 100 mg capsules. There will be matched placebo-minocycline capsules for each minocycline capsule strength. During the first week subjects will receive one 50 mg capsule twice per day (minocycline 100 mg total or matching placebo) and during weeks 2-10 subjects will receive 2- 50 mg capsules twice per day If a subject should complain of any side effect, then the blind psychiatrist will be allowed to omit the next dose of study medication and then continue the subject on the optimal treatment dose. If, despite this intervention, the subject is still unable to tolerate the 200 mg/day dose, then the dose may be lowered to 150 mg to alleviate side effects and minimize attrition.

Placebo Comparator: Sugar Pill Drug: Placebo

Placebo Dosing:

Minocycline (Dynacin® or generic) will be available in 50, 75 and 100 mg capsules. There will be matched placebo-minocycline capsules for each minocycline capsule strength. During the first week subjects will receive one 50 mg capsule twice per day(minocycline 100 mg total or matching placebo) and during weeks 2-10 subjects will receive 2- 50 mg capsules twice per day If a subject should complain of any side effect, then the blind psychiatrist will be allowed to omit the next dose of study medication and then continue the subject on the optimal treatment dose. If, despite this intervention, the subject is still unable to tolerate the 200 mg/day dose, then the dose may be lowered to 150 mg to alleviate side effects and minimize attrition.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV diagnosis of schizophrenia or schizoaffective disorder
  • Male or Female
  • Age: 18 to 65 years
  • Caucasian or Non-Caucasian
  • At least six months of clozapine treatment
  • Clozapine treatment for incomplete symptoms response (evidence of two failed previous trials of antipsychotics)
  • Current dose of 200 mg/day for at least 3 months AND a documented clozapine blood level 350 ng/ml prior to study start (maximum clozapine dose of 900 mg/day)
  • BPRS total score of 45 or more on the 18 item version (scale: 1-7)
  • BPRS positive symptom item total score of 8 or more
  • BPRS positive symptom score of 4 or greater on at least one item

Exclusion Criteria:

  • History of organic brain disease
  • DSM-IV diagnosis of Mental Retardation
  • DSM-IV diagnosis of Alcohol or Substance Dependence within the last six months (except nicotine)
  • DSM-IV diagnosis of Alcohol or Substance Abuse within the last one month (except nicotine)
  • Pregnancy or lactation
  • Significant renal or liver impairment
  • Previous known hypersensitivity to tetracyclines
  • Current treatment with tetracycline or derivative
  • Current treatment with lamotrigine
  • Treatment with oral contraceptives
  • Current known infection
  • Treatment with cholestyramine or colestipol
  • Treatment with Urinary alkalinizers (e.g., sodium lactate, potassium citrate)
  • Treatment with warfarin
  • Abnormal (considered positive) Lyme titer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433055

Locations
United States, Maryland
Maryland Psychiatric Research Center
Catonsville, Maryland, United States, 21228
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Deanna Kelly, Pharm.D., BCPP University of Maryland
  More Information

No publications provided

Responsible Party: MPRC, Deanna L. Kelly, Pharm.D., BCPP, University of Maryland
ClinicalTrials.gov Identifier: NCT01433055     History of Changes
Other Study ID Numbers: HP-00048900, 1R21 MH091184-01A1
Study First Received: July 21, 2011
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
Schizophrenia
Cognitive Symptoms
Clozapine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Minocycline
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 21, 2014