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Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia

Primary Purpose

Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Status

Recruiting

Phase

Phase 1

Locations

Pakistan

Study Type

Interventional

Intervention

Minocycline

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Anti-inflammatory, Clozapine, Minocycline, Psychosis NOS

Eligibility Criteria

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

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

Sites / Locations

Abasi Shaheed HospitalRecruiting
Civil hospital KarachiRecruiting
Karwn e HayatRecruiting
Institute of Behavioral SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

placebo

Minocycline

Arm Description

Matching placebo for Minocycline

Minocycline 200mg once a day orally

Outcomes

Primary Outcome Measures

Positive and Negative Syndrome Scale PANSS

PANSS is an assessment measures to assess severity of symptoms of schizophrenia

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02533232

First Posted

August 24, 2015

Last Updated

April 22, 2022

Sponsor

Pakistan Institute of Living and Learning

1. Study Identification

Unique Protocol Identification Number

NCT02533232

Brief Title

Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia

Official Title

Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia: A Randomised Placebo-controlled Double-blind Trial

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 30, 2022 (Anticipated)

Primary Completion Date

December 30, 2022 (Anticipated)

Study Completion Date

December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pakistan Institute of Living and Learning

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Keywords

Schizophrenia, Anti-inflammatory, Clozapine, Minocycline, Psychosis NOS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo for Minocycline

Arm Title

Minocycline

Arm Type

Experimental

Arm Description

Minocycline 200mg once a day orally

Intervention Type

Drug

Intervention Name(s)

Minocycline

Other Intervention Name(s)

Mesodrum

Intervention Description

Minocycline 200mg per day

Primary Outcome Measure Information:

Title

Positive and Negative Syndrome Scale PANSS

Description

PANSS is an assessment measures to assess severity of symptoms of schizophrenia

Time Frame

3 months

Secondary Outcome Measure Information:

Title

CogState

Description

Time Frame

3 Month

Other Pre-specified Outcome Measures:

Title

Social Functioning Scale

Description

Self-rating questionnaire assessing social functioning in 7 domains.

Time Frame

3 Month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dr.Inti Qurashi, MD

Inti.Qurashi@merseycare.nhs.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Prof.Imran B Chaudhry, MD

Phone

02135871845

ibchaudhry@btinternet.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dr.Inti Qurashi, MD

Organizational Affiliation

Manchester University ,UK

Official's Role

Principal Investigator

Facility Information:

Facility Name

Abasi Shaheed Hospital

City

Karachi

State/Province

Sindh

ZIP/Postal Code

72000

Country

Pakistan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Prof Munir Hamarani, FCPS

Phone

00923009272002

mmham@yahoo.com

First Name & Middle Initial & Last Name & Degree

Prof Munir Hamarani, FCPS

Facility Name

Civil hospital Karachi

City

Karachi

State/Province

Sindh

ZIP/Postal Code

72000

Country

Pakistan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Prof Raza U Rahman, FCPS

Phone

00-92-21-9215740-50

Ext

2500

razaur@yahoo.com

First Name & Middle Initial & Last Name & Degree

Prof Raza U Rahman, FCPS

Facility Name

Karwn e Hayat

City

Karachi

State/Province

Sindh

ZIP/Postal Code

72000

Country

Pakistan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dr Ajmal Kazmi, MRCPsych

Phone

00923213783890

kazmiajmal@yahoo.com

First Name & Middle Initial & Last Name & Degree

Dr Ajmal Kazmi

Facility Name

Institute of Behavioral Sciences

City

Karachi

State/Province

Sindh

Country

Pakistan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shehla Ahmed

12. IPD Sharing Statement

Citations:

PubMed Identifier

24646811

Citation

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.

Results Reference

background

PubMed Identifier

9366002

Citation

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

Results Reference

background

PubMed Identifier

11282684

Citation

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.

Results Reference

background

PubMed Identifier

15925493

Citation

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.

Results Reference

background

PubMed Identifier

21422107

Citation

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.

Results Reference

background

PubMed Identifier

9690329

Citation

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.

Results Reference

background

PubMed Identifier

18534557

Citation

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.

Results Reference

background

PubMed Identifier

14684440

Citation

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.

Results Reference

background

PubMed Identifier

1654746

Citation

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.

Results Reference

background

PubMed Identifier

19695284

Citation

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.

Results Reference

background

PubMed Identifier

23012427

Citation

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.

Results Reference

background

PubMed Identifier

18250253

Citation

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.

Results Reference

background

PubMed Identifier

9524789

Citation

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

Results Reference

background

PubMed Identifier

15530637

Citation

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

Results Reference

background

PubMed Identifier

11306611

Citation

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.

Results Reference

background

Links:

URL

http://pill.org.pk

Description

Website of Pakistan Institute of Learning and Living

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Minocycline Augmentation of Clozapine for Treatment Resistant Schizophrenia

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