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Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

Primary Purpose

Schizophrenia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Minocycline
Placebo
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Cognitive Symptoms, Clozapine

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Maryland Psychiatric Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Minocycline

Sugar Pill

Arm Description

Outcomes

Primary Outcome Measures

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.
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.

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)
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
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.
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.

Full Information

First Posted
July 21, 2011
Last Updated
August 15, 2019
Sponsor
University of Maryland, Baltimore
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT01433055
Brief Title
Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
Official Title
Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Cognitive Symptoms, Clozapine

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Minocycline
Arm Type
Active Comparator
Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Minocycline
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo.
Description
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.
Time Frame
10 Weeks
Title
Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery.
Description
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.
Time Frame
10 Weeks
Secondary Outcome Measure Information:
Title
The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS)
Description
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.
Time Frame
10 Weeks
Title
The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale
Description
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.
Time Frame
10 Weeks
Title
The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms.
Description
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.
Time Frame
10 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deanna Kelly, Pharm.D., BCPP
Organizational Affiliation
University of Maryland, College Park
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maryland Psychiatric Research Center
City
Catonsville
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26082974
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.
Results Reference
derived

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Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

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