SchizophreniaNCT01433055
Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
A study testing Minocycline in people with Schizophrenia, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Jan 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Maryland Psychiatric Research Center
Catonsville, Maryland, 21228
About this study
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
- Being tested
- Minocycline, Placebo
- Keywords
- Schizophrenia, Cognitive Symptoms, Clozapine
- Medical subject headings
- Schizophrenia, Neurobehavioral Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Minocycline | Active comparator | Not described Receives: Drug: Minocycline |
| Sugar Pill | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
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.
Measured: 10 Weeks
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.
Measured: 10 Weeks
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.
Measured: 10 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, MPRC, University of Maryland, Baltimore
- Investigators
- Deanna Kelly, Pharm.D., BCPP, Principal investigator, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01433055
- Sponsor's protocol ID
- HP-00048900
- Other IDs
- 1R21MH091184-01A1
- Status last verified
- Aug 2019
- First submitted
- 21 Jul 2011
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26082974
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Minocycline in Clozapine Treated Schizophrenia Patients
- ClinicalTrials.gov ID
- NCT01433055
- Acronym / sponsor ID
- HP-00048900
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Cognitive Symptoms, Clozapine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jul 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 13 Sep 2011 (estimated)
- Results
- Posted 9 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Active comparator | Drug: Minocycline |
| Sugar Pill | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineMinocycline 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. | Drug | Minocycline |
| PlaceboPlacebo 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. | Drug | Sugar Pill |
Primary outcome
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo.
Time frame: 10 Weeks
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.
Time frame: 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.
3 secondary outcomes
The Effect of Minocycline Compared to Placebo to Improve Negative Symptoms as Measured by the Scale for the Assessment of Negative Symptoms (SANS)
Time frame: 10 Weeks
The Effect of Adjunct Minocycline to Placebo to Improve Depressive Symptoms as Measured by the Calgary Depression Scale
Time frame: 10 Weeks
The Effect of Adjunct Minocycline to Placebo on Global Clinical Improvement of Symptoms.
Time frame: 10 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26082974Kelly 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.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deanna Kelly, Pharm.D., BCPP principal investigator
University of Maryland, College Park
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Minocycline in people with Schizophrenia, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brief Psychiatric Rating Scale (BPRS) Positive Symptom Domain Scores Between Minocycline and Placebo. (time frame: 10 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01433055, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.