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Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
MPRC, University of Maryland
ClinicalTrials.gov Identifier:
NCT01433055
First received: July 21, 2011
Last updated: June 7, 2017
Last verified: June 2017
  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
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

Resource links provided by NLM:


Further study details as provided by MPRC, University of Maryland:

Primary Outcome Measures:
  • Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo. [ Time Frame: 10 Weeks ]
    Adjunct minocycline to clozapine will be compared to placebo to test its efficacy to improve positive psychotic symptoms. The 4 item positive sub factor of the Brief Psychiatric Rating Scale (BPRS) will be the primary outcome over the 10 week randomized study. Total maximum score is 28, and total minimum score is 4. The positive domain score consists of conceptual disorganization (item 4), suspiciousness (item 11) hallucinatory behavior (item 12), and unusual thought content (item 15). All data is reported as the difference between baseline and 10 weeks. The lower the score the better the outcome.

  • Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery. [ Time Frame: 10 Weeks ]
    Adjunct minocycline 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. This assessment total minimum score of -10 and maximum score of 80. He higher the score the better the outcome.


Secondary Outcome Measures:
  • The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) [ Time Frame: 10 Weeks ]
    Adjunct minocycline 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. This assessment has 22 items (scored 0-5) with a total minimum score of 0 and maximum score of 110. The lower the score the better the outcome.

  • The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale [ Time Frame: 10 Weeks ]
    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. This assessment has 9 items (scored 0-3) with a total minimum socre of 0 and maximum score of 27. The lower the score the better the outcome.

  • The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms. [ Time Frame: 10 Weeks ]
    The Clinical Global Impression Severity score will be used to examine the effect of minocycline compared to placebo. This assessment has 2 items (scored 0-7) with a total minimum socre of 0 and maximum score of 14. The lower the score the better the outcome.


Enrollment: 52
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   (Adult)
Sexes Eligible for Study:   All
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
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Deanna Kelly, Pharm.D., BCPP University of Maryland
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
1R21MH091184-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: July 21, 2011
Results First Received: May 16, 2016
Last Updated: June 7, 2017

Keywords provided by MPRC, University of Maryland:
Schizophrenia
Cognitive Symptoms
Clozapine

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

ClinicalTrials.gov processed this record on June 23, 2017