Clinical trial NCT01433055: Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
Official title: Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: Schizophrenia
Cognitive Symptoms
Clozapine
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2011-09-13
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo.
timeFrame: 10 Weeks
measure: Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery.
timeFrame: 10 Weeks
Secondary outcomes:
measure: The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS)
timeFrame: 10 Weeks
measure: The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale
timeFrame: 10 Weeks
measure: The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms.
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: Catonsville
country: United States
facility: Maryland Psychiatric Research Center
state: Maryland
Study officials:
affiliation: University of Maryland, College Park
name: Deanna Kelly, Pharm.D., BCPP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.