Trial Outcomes & Findings for Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients (NCT NCT01433055)

Last Updated: 2019-08-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

52 participants

Primary outcome timeframe

10 Weeks

Results posted on

2019-08-28

Participant Flow

Participant milestones

Participant milestones
Measure	Minocycline 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.	Sugar Pill 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.
Overall Study STARTED	29	23
Overall Study COMPLETED	27	23
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Minocycline 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.	Sugar Pill 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.
Overall Study Diagnosed with cancer unrelated to study	1	0
Overall Study Severely elevated triglycerides at entry	1	0

Baseline Characteristics

Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.	Total n=50 Participants Total of all reporting groups
Age, Continuous	42.9 years STANDARD_DEVIATION 14.2 • n=5 Participants	42.3 years STANDARD_DEVIATION 11.0 • n=7 Participants	42.6 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized White	17 participants n=5 Participants	13 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized Black	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	23 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 10 Weeks

Population: The BPRS is a scale that measures major psychotic and non psychotic symptoms in persons with psychotic disorders. It is an 4 item scale with a score range of 1-7 on each item. Results are reported as total score. Total maximum score is 28, and total minimum score is 4.

Outcome measures

Outcome measures
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo. Baseline	14.5 units on a scale Standard Deviation 3.5	14.5 units on a scale Standard Deviation 3.5
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo. 10 weeks (Endpoint)	12.9 units on a scale Standard Deviation 3.2	14.2 units on a scale Standard Deviation 3.2

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.
Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery. Baseline	30.4 units on a scale Standard Deviation 11.6	35.1 units on a scale Standard Deviation 11.7
Effect of Minocycline on Cognitive Symptoms as Measured by the MATRICS Consensus Cognitive Battery. 10 Weeks (Endpoint)	35.6 units on a scale Standard Deviation 10.7	34.2 units on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.
The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS) Baseline	29.7 units on a scale Standard Deviation 13.3	33.3 units on a scale Standard Deviation 10.3
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 (Endpoint)	28.2 units on a scale Standard Deviation 12.4	35.1 units on a scale Standard Deviation 10.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.
The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale Baseline	3.3 units on a scale Standard Deviation 3.1	2.6 units on a scale Standard Deviation 2.7
The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale 10 Weeks (Endpoint)	2.4 units on a scale Standard Deviation 3.0	2.9 units on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Minocycline n=27 Participants 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.	Sugar Pill n=23 Participants 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.
The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms. Baseline	4.0 units on a scale Standard Deviation 0	4.0 units on a scale Standard Deviation 0.1
The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms. 10 Weeks (Endpoint)	3.6 units on a scale Standard Deviation 0.6	4.0 units on a scale Standard Deviation 0.7

Adverse Events

Minocycline

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Minocycline n=27 participants at risk 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.	Sugar Pill n=23 participants at risk 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.
Gastrointestinal disorders Nausea	40.7% 11/27	34.8% 8/23
Musculoskeletal and connective tissue disorders Abdominal Pain	29.6% 8/27	26.1% 6/23
Gastrointestinal disorders Vomiting	25.9% 7/27	13.0% 3/23
Metabolism and nutrition disorders Weight loss	18.5% 5/27	26.1% 6/23
Gastrointestinal disorders Diarrhea	18.5% 5/27	30.4% 7/23
Gastrointestinal disorders Constipation	11.1% 3/27	43.5% 10/23
Nervous system disorders Malaise	29.6% 8/27	26.1% 6/23
Nervous system disorders Sedation	11.1% 3/27	13.0% 3/23
Nervous system disorders Dizziness	25.9% 7/27	21.7% 5/23
Nervous system disorders Restlessness	25.9% 7/27	21.7% 5/23
General disorders Salivation	22.2% 6/27	21.7% 5/23
Nervous system disorders Insomnia	18.5% 5/27	21.7% 5/23
General disorders Headache	14.8% 4/27	43.5% 10/23
Skin and subcutaneous tissue disorders Rash	14.8% 4/27	4.3% 1/23
Musculoskeletal and connective tissue disorders Stiffness	14.8% 4/27	21.7% 5/23
General disorders Dry Mouth	11.1% 3/27	26.1% 6/23
Skin and subcutaneous tissue disorders Urticaria	11.1% 3/27	4.3% 1/23

Additional Information

Deanna L. Kelly, Pharm.D., BCPP

Maryland Psychiatric Research Center

Phone: 410-402-6861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place