SchizophreniaPhase 1NCT02533232
Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia
A Phase 1 study testing Minocycline in people with Schizophrenia and Schizoaffective Disorder, run by Pakistan Institute of Living and Learning at 4 sites in Pakistan.
Trial summary
This a randomized double-blind placebo controlled trial which aims to determine the beneficial effects of minocycline augmentation to clozapine in partial responders to Treatment Resistant Schizophrenia (TRS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
- 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
- 60 participants
- Where
- 4 sitesPakistan
- Study dates
- 30 Aug 2022to 30 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Male and female patients aged between 18-65 years, IQ >70 (to complete assessments) identified by treating psychiatrist.
- Confirmation of schizophrenia by using The MINI psychiatric interview (at baseline only)
- Assessed as competent to provide informed consent by treating psychiatrist.
- Antipsychotic medication has remained stable 4 weeks prior to baseline *. Assessed as a partial responder to clozapine: patients prescribed clozapine at a stable therapeutic dose for a minimum of 3 months with total Positive and Negative Syndrome Schizophrenia (PANSS) score >70.
Who cannot join
- Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the Tetracyclines.
- Concomitant Penicillin therapy or concomitant anticoagulant therapy.
- Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to ICD 10 criteria.
- Treatment with Warfarin or Lamotrigine.
- Current or previous treatment with minocycline or other tetracycline antibiotics in the preceding three months before study entry.
- Relevant current or past hematologic, hepatic, renal, neurological or other medical disorder that in the opinion of the principal investigator may interfere with the study.
- Pregnant or breast-feeding females
Trial locations and contacts
4 sites in 1 country.
Dr.Inti Qurashi, MD contact
Pakistan4 sites, 4 recruiting
- Recruiting
Abasi Shaheed Hospital
Karachi, Sindh, 72000
Prof Munir Hamarani, FCPS, 00923009272002, mmham@yahoo.com
Prof Munir Hamarani, FCPS
- Recruiting
Civil hospital Karachi
Karachi, Sindh, 72000
Prof Raza U Rahman, FCPS, 00-92-21-9215740-50 ext. 2500, razaur@yahoo.com
Prof Raza U Rahman, FCPS
- Recruiting
Karwn e Hayat
Karachi, Sindh, 72000
Dr Ajmal Kazmi, MRCPsych, 00923213783890, kazmiajmal@yahoo.com
Dr Ajmal Kazmi
- Recruiting
Institute of Behavioral Sciences
Karachi, Sindh
Shehla Ahmed
About this study
Official title: Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial
This a randomized double-blind placebo controlled trial which aims to determine the beneficial effects of minocycline augmentation to clozapine in partial responders to Treatment Resistant Schizophrenia (TRS).
Read the detailed description
The primary objective is to determine if the addition of minocycline to Clozapine, Treatment as Usual (TAU) Improves negative symptoms and/or positive symptoms.
The secondary objectives are to determine:
- Effects on cognitive functioning.
- Effects on social functioning and quality of life.
- Safety and tolerability.
- Possible additive effects of Minocycline added to TAU
- The effect on inflammatory biomarkers associated with schizophrenia. Both pro and anti-inflammatory cytokines will be drawn at baseline and endpoint. We will test to see if minocycline is associated with improvements in abnormal cytokines as compared to placebo.
The study will be a randomized double-blind placebo controlled trial of minocycline added to clozapine (Treatment as Usual) in TRS. There will be two treatment arms: one arm receiving TAU with minocycline and the other TAU with placebo for a period of twelve weeks.
- Being tested
- Minocycline
- Keywords
- Schizophrenia, Anti-inflammatory, Clozapine, Minocycline, Psychosis NOS
- Medical subject headings
- Schizophrenia, Psychotic Disorders, cyclopia sequence, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Mesodrum
Minocycline 200mg per day
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | Matching placebo for Minocycline Receives: Drug: Minocycline |
| Minocycline | Experimental | Minocycline 200mg once a day orally Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive and Negative Syndrome Scale PANSS
PANSS is an assessment measures to assess severity of symptoms of schizophrenia
Measured: 3 months
Secondary outcomes (1)
CogState
Measuring all seven domains recommended by MATRICS (NIMH initiative). These domains include speed processing, attention/vigilance, Working memory (nonverbal \& verbal), verbal learning, visual learning, reasoning and problem solving and social cognition's.
Measured: 3 Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2015 (estimated)
- Study start30 Aug 2022 (estimated)
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pakistan Institute of Living and Learning
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dr.Inti Qurashi, MD, Principal investigator, Manchester University ,UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02533232
- Sponsor's protocol ID
- PILL-MAC-001
- Status last verified
- Apr 2022
- First submitted
- 24 Aug 2015
- Last updated
- 29 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Qurashi I, Collins JD, Chaudhry IB, Husain N. Promising use of minocycline augmentation with clozapine in treatment-resistant schizophrenia. J Psychopharmacol. 2014 Jul;28(7):707-8. doi: 10.1177/0269881114527358. Epub 2014 Mar 19.
PubMed 24646811Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997;23(4):663-74. doi: 10.1093/schbul/23.4.663.
PubMed 9366002Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 2001 Apr;158(4):518-26. doi: 10.1176/appi.ajp.158.4.518.
PubMed 11282684Rossler W, Salize HJ, van Os J, Riecher-Rossler A. Size of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol. 2005 Aug;15(4):399-409. doi: 10.1016/j.euroneuro.2005.04.009.
PubMed 15925493Sommer IE, Begemann MJ, Temmerman A, Leucht S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. 2012 Sep;38(5):1003-11. doi: 10.1093/schbul/sbr004. Epub 2011 Mar 21.
PubMed 21422107Lin A, Kenis G, Bignotti S, Tura GJ, De Jong R, Bosmans E, Pioli R, Altamura C, Scharpe S, Maes M. The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res. 1998 Jun 22;32(1):9-15. doi: 10.1016/s0920-9964(98)00034-6.
PubMed 9690329van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008 Nov 1;64(9):820-2. doi: 10.1016/j.biopsych.2008.04.025. Epub 2008 Jun 4.
PubMed 18534557Farber NB. The NMDA receptor hypofunction model of psychosis. Ann N Y Acad Sci. 2003 Nov;1003:119-30. doi: 10.1196/annals.1300.008.
PubMed 14684440Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991 Oct;148(10):1301-8. doi: 10.1176/ajp.148.10.1301.
PubMed 1654746Labrie V, Roder JC. The involvement of the NMDA receptor D-serine/glycine site in the pathophysiology and treatment of schizophrenia. Neurosci Biobehav Rev. 2010 Mar;34(3):351-72. doi: 10.1016/j.neubiorev.2009.08.002. Epub 2009 Aug 18.
PubMed 19695284Anticevic A, Gancsos M, Murray JD, Repovs G, Driesen NR, Ennis DJ, Niciu MJ, Morgan PT, Surti TS, Bloch MH, Ramani R, Smith MA, Wang XJ, Krystal JH, Corlett PR. NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16720-5. doi: 10.1073/pnas.1208494109. Epub 2012 Sep 25.
PubMed 23012427Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM. Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry. 2008 Feb;65(2):154-64. doi: 10.1001/archgenpsychiatry.2007.37.
PubMed 18250253Meltzer HY. Treatment-resistant schizophrenia--the role of clozapine. Curr Med Res Opin. 1997;14(1):1-20. doi: 10.1185/03007999709113338.
PubMed 9524789Domercq M, Matute C. Neuroprotection by tetracyclines. Trends Pharmacol Sci. 2004 Dec;25(12):609-12. doi: 10.1016/j.tips.2004.10.001.
PubMed 15530637Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001 Apr 15;21(8):2580-8. doi: 10.1523/JNEUROSCI.21-08-02580.2001.
PubMed 11306611
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial
- ClinicalTrials.gov ID
- NCT02533232
- Acronym / sponsor ID
- PILL-MAC-001
- Keywords
- Schizophrenia, Anti-inflammatory, Clozapine, Minocycline, Psychosis NOS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Pakistan Institute of Living and LearningUniversity, hospital or other
- Study start
- 30 Aug 2022 (estimated)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 26 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This a randomized double-blind placebo controlled trial which aims to determine the beneficial effects of minocycline augmentation to clozapine in partial responders to Treatment Resistant Schizophrenia (TRS).
Detailed description
The primary objective is to determine if the addition of minocycline to Clozapine, Treatment as Usual (TAU) Improves negative symptoms and/or positive symptoms.
The secondary objectives are to determine:
- Effects on cognitive functioning.
- Effects on social functioning and quality of life.
- Safety and tolerability.
- Possible additive effects of Minocycline added to TAU
- The effect on inflammatory biomarkers associated with schizophrenia. Both pro and anti-inflammatory cytokines will be drawn at baseline and endpoint. We will test to see if minocycline is associated with improvements in abnormal cytokines as compared to placebo.
The study will be a randomized double-blind placebo controlled trial of minocycline added to clozapine (Treatment as Usual) in TRS. There will be two treatment arms: one arm receiving TAU with minocycline and the other TAU with placebo for a period of twelve weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: MinocyclineMatching placebo for Minocycline |
| Minocycline | Experimental | Drug: MinocyclineMinocycline 200mg once a day orally |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients aged between 18-65 years, IQ >70 (to complete assessments) identified by treating psychiatrist.
- Confirmation of schizophrenia by using The MINI psychiatric interview (at baseline only)
- Assessed as competent to provide informed consent by treating psychiatrist.
- Antipsychotic medication has remained stable 4 weeks prior to baseline *. Assessed as a partial responder to clozapine: patients prescribed clozapine at a stable therapeutic dose for a minimum of 3 months with total Positive and Negative Syndrome Schizophrenia (PANSS) score >70.
Key exclusion criteria (7 listed)
- Prior history of intolerance or serious side effects (hepatotoxicity, photosensitivity, blood dyscrasias) to any of the Tetracyclines.
- Concomitant Penicillin therapy or concomitant anticoagulant therapy.
- Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to ICD 10 criteria.
- Treatment with Warfarin or Lamotrigine.
- Current or previous treatment with minocycline or other tetracycline antibiotics in the preceding three months before study entry.
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 |
|---|---|---|
| MinocyclineAlso: MesodrumMinocycline 200mg per day | Drug | Minocycline, placebo |
Primary outcome
Positive and Negative Syndrome Scale PANSS
Time frame: 3 months
PANSS is an assessment measures to assess severity of symptoms of schizophrenia
1 secondary outcome
CogState
Time frame: 3 Month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
- Background: PubMed 24646811Qurashi I, Collins JD, Chaudhry IB, Husain N. Promising use of minocycline augmentation with clozapine in treatment-resistant schizophrenia. J Psychopharmacol. 2014 Jul;28(7):707-8. doi: 10.1177/0269881114527358. Epub 2014 Mar 19.
- Background: PubMed 9366002Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997;23(4):663-74. doi: 10.1093/schbul/23.4.663.
- Background: PubMed 11282684Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 2001 Apr;158(4):518-26. doi: 10.1176/appi.ajp.158.4.518.
- Background: PubMed 15925493Rossler W, Salize HJ, van Os J, Riecher-Rossler A. Size of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol. 2005 Aug;15(4):399-409. doi: 10.1016/j.euroneuro.2005.04.009.
- Background: PubMed 21422107Sommer IE, Begemann MJ, Temmerman A, Leucht S. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull. 2012 Sep;38(5):1003-11. doi: 10.1093/schbul/sbr004. Epub 2011 Mar 21.
- Background: PubMed 9690329Lin A, Kenis G, Bignotti S, Tura GJ, De Jong R, Bosmans E, Pioli R, Altamura C, Scharpe S, Maes M. The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res. 1998 Jun 22;32(1):9-15. doi: 10.1016/s0920-9964(98)00034-6.
- Background: PubMed 18534557van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E, Luurtsema G, Windhorst AD, Cahn W, Lammertsma AA, Kahn RS. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry. 2008 Nov 1;64(9):820-2. doi: 10.1016/j.biopsych.2008.04.025. Epub 2008 Jun 4.
- Background: PubMed 14684440Farber NB. The NMDA receptor hypofunction model of psychosis. Ann N Y Acad Sci. 2003 Nov;1003:119-30. doi: 10.1196/annals.1300.008.
- Background: PubMed 1654746Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991 Oct;148(10):1301-8. doi: 10.1176/ajp.148.10.1301.
- Background: PubMed 19695284Labrie V, Roder JC. The involvement of the NMDA receptor D-serine/glycine site in the pathophysiology and treatment of schizophrenia. Neurosci Biobehav Rev. 2010 Mar;34(3):351-72. doi: 10.1016/j.neubiorev.2009.08.002. Epub 2009 Aug 18.
- Background: PubMed 23012427Anticevic A, Gancsos M, Murray JD, Repovs G, Driesen NR, Ennis DJ, Niciu MJ, Morgan PT, Surti TS, Bloch MH, Ramani R, Smith MA, Wang XJ, Krystal JH, Corlett PR. NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16720-5. doi: 10.1073/pnas.1208494109. Epub 2012 Sep 25.
- Background: PubMed 18250253Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM. Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry. 2008 Feb;65(2):154-64. doi: 10.1001/archgenpsychiatry.2007.37.
- Website of Pakistan Institute of Learning and LivingLink provided by the sponsor.
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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.
Dr.Inti Qurashi, MD contact
Dr.Inti Qurashi, MD principal investigator
Manchester University ,UK
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Minocycline in people with Schizophrenia and Schizoaffective Disorder, run by Pakistan Institute of Living and Learning at 4 sites in Pakistan.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Pakistan. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr.Inti Qurashi, MD (Inti.Qurashi@merseycare.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positive and Negative Syndrome Scale PANSS (time frame: 3 months). 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 NCT02533232, which also lists 15 linked publications.
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 29 Apr 2022.