Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
2 other identifiers
interventional
52
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable schizophrenia
Started Jul 2011
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2011
CompletedFirst Submitted
Initial submission to the registry
July 21, 2011
CompletedFirst Posted
Study publicly available on registry
September 13, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2014
CompletedResults Posted
Study results publicly available
June 9, 2017
CompletedAugust 28, 2019
August 1, 2019
2.5 years
July 21, 2011
May 16, 2016
August 15, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo.
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.
10 Weeks
Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery.
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.
10 Weeks
Secondary Outcomes (3)
The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS)
10 Weeks
The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale
10 Weeks
The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms.
10 Weeks
Study Arms (2)
Minocycline
ACTIVE COMPARATORSugar Pill
PLACEBO COMPARATORInterventions
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 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 Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Maryland Psychiatric Research Center
Catonsville, Maryland, 21228, United States
Related Publications (1)
Kelly DL, Sullivan KM, McEvoy JP, McMahon RP, Wehring HJ, Gold JM, Liu F, Warfel D, Vyas G, Richardson CM, Fischer BA, Keller WR, Koola MM, Feldman SM, Russ JC, Keefe RS, Osing J, Hubzin L, August S, Walker TM, Buchanan RW. Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms. J Clin Psychopharmacol. 2015 Aug;35(4):374-81. doi: 10.1097/JCP.0000000000000345.
PMID: 26082974DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Deanna L. Kelly, Pharm.D., BCPP
- Organization
- Maryland Psychiatric Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Deanna Kelly, Pharm.D., BCPP
University of Maryland, College Park
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Deanna L. Kelly, Pharm.D., BCPP
Study Record Dates
First Submitted
July 21, 2011
First Posted
September 13, 2011
Study Start
July 1, 2011
Primary Completion
January 1, 2014
Study Completion
January 1, 2014
Last Updated
August 28, 2019
Results First Posted
June 9, 2017
Record last verified: 2019-08