Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

NCT ID: NCT01433055

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-01-31

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Minocycline

Group Type: ACTIVE_COMPARATOR

Minocycline

Intervention Type: DRUG

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.

Sugar Pill

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

MPRC

Deanna L. Kelly, Pharm.D., BCPP

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deanna Kelly, Pharm.D., BCPP

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Locations

Maryland Psychiatric Research Center

Catonsville, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26082974 (View on PubMed)

Other Identifiers

1R21MH091184-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00048900

Identifier Type: -

Identifier Source: org_study_id