Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia

NCT ID: NCT02533232

Last Updated: 2022-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-30

Study Completion Date

2022-12-30

Brief Summary

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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

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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.

Conditions

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Schizophrenia Schizoaffective Disorder Schizophreniform Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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placebo

Matching placebo for Minocycline

Group Type PLACEBO_COMPARATOR

Minocycline

Intervention Type DRUG

Minocycline 200mg per day

Minocycline

Minocycline 200mg once a day orally

Group Type EXPERIMENTAL

Minocycline

Intervention Type DRUG

Minocycline 200mg per day

Interventions

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Minocycline

Minocycline 200mg per day

Intervention Type DRUG

Other Intervention Names

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Mesodrum

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pakistan Institute of Living and Learning

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr.Inti Qurashi, MD

Role: PRINCIPAL_INVESTIGATOR

Manchester University ,UK

Locations

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Abasi Shaheed Hospital

Karachi, Sindh, Pakistan

Site Status RECRUITING

Civil hospital Karachi

Karachi, Sindh, Pakistan

Site Status RECRUITING

Karwn e Hayat

Karachi, Sindh, Pakistan

Site Status RECRUITING

Institute of Behavioral Sciences

Karachi, Sindh, Pakistan

Site Status RECRUITING

Countries

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Pakistan

Central Contacts

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Dr.Inti Qurashi, MD

Role: CONTACT

Prof.Imran B Chaudhry, MD

Role: CONTACT

02135871845

Facility Contacts

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Prof Munir Hamarani, FCPS

Role: primary

00923009272002

Prof Raza U Rahman, FCPS

Role: primary

00-92-21-9215740-50 ext. 2500

Dr Ajmal Kazmi, MRCPsych

Role: primary

00923213783890

Shehla Ahmed

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 24646811 (View on PubMed)

Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 1997;23(4):663-74. doi: 10.1093/schbul/23.4.663.

Reference Type BACKGROUND
PMID: 9366002 (View on PubMed)

Chakos 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.

Reference Type BACKGROUND
PMID: 11282684 (View on PubMed)

Rossler 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.

Reference Type BACKGROUND
PMID: 15925493 (View on PubMed)

Sommer 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.

Reference Type BACKGROUND
PMID: 21422107 (View on PubMed)

Lin 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.

Reference Type BACKGROUND
PMID: 9690329 (View on PubMed)

van 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.

Reference Type BACKGROUND
PMID: 18534557 (View on PubMed)

Farber NB. The NMDA receptor hypofunction model of psychosis. Ann N Y Acad Sci. 2003 Nov;1003:119-30. doi: 10.1196/annals.1300.008.

Reference Type BACKGROUND
PMID: 14684440 (View on PubMed)

Javitt 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.

Reference Type BACKGROUND
PMID: 1654746 (View on PubMed)

Labrie 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.

Reference Type BACKGROUND
PMID: 19695284 (View on PubMed)

Anticevic 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.

Reference Type BACKGROUND
PMID: 23012427 (View on PubMed)

Deakin 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.

Reference Type BACKGROUND
PMID: 18250253 (View on PubMed)

Meltzer HY. Treatment-resistant schizophrenia--the role of clozapine. Curr Med Res Opin. 1997;14(1):1-20. doi: 10.1185/03007999709113338.

Reference Type BACKGROUND
PMID: 9524789 (View on PubMed)

Domercq M, Matute C. Neuroprotection by tetracyclines. Trends Pharmacol Sci. 2004 Dec;25(12):609-12. doi: 10.1016/j.tips.2004.10.001.

Reference Type BACKGROUND
PMID: 15530637 (View on PubMed)

Tikka 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.

Reference Type BACKGROUND
PMID: 11306611 (View on PubMed)

Related Links

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http://pill.org.pk

Website of Pakistan Institute of Learning and Living

Other Identifiers

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PILL-MAC-001

Identifier Type: -

Identifier Source: org_study_id

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