Role of Minocycline in First Episode Psychosis

NCT00916461 | Completed Phase 1

• 1 other identifier: SMRI 04T-583
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to determine whether the addition of minocycline or placebo to treatment as usual (TAU):

1. 1.prevents the accumulation of negative symptoms and intellectual decline following a first episode of non-affective psychosis; and
2. 2.whether minocycline stabilizes the efficacy of antipsychotics.

Conditions

First Episode Psychosis

Keywords

First episode psychosis; Schizophrenia; Minocycline; neuroprotection; First episode non affective psychosis; With in first five years of illness

Outcome Measures

Primary Outcomes (1)

• Positive and negative symptoms on Positive and Negative Syndrome Scale (PANSS)

  Baseline and 12 months

Secondary Outcomes (6)

• Clinical Global Impression (CGI)

  Baseline and 12 months

• Global Assessment of Functioning (GAF)

  Baseline and 12 months

• Abnormal Involuntary Movement Scale (AIMS)

  Baseline and 12 months

• Assessment of side effects

  Baseline and 12 months

• Doses of antipsychotic drugs

  Baseline and 12 months

Study Arms (2)

Minocycline

ACTIVE COMPARATOR

Drug: Minocycline

Sugar Pill

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Minocycline DRUG

Minocycline + treatment as usual. 50 mg twice daily increasing to 200 mgs per day, increments of 50 mgs every 2 weeks.

Minocycline

Placebo DRUG

Placebo + treatment as usual.

Sugar Pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 65 years
• Diagnostic and Statistical Manual-IV (DSM-IV) diagnosed first episode psychosis, schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder
• First episode (within first 5 years of diagnosis)
• Competent and willing to give informed consent
• Medication remained stable 4 weeks prior to baseline
• Able to take oral medication and likely to complete the required evaluations
• Female participants of child bearing capability must be willing to use adequate contraceptives for the duration of the study, and, willing to have a pregnancy test pre-treatment and at ten weekly intervals while on study medication

You may not qualify if:

• Relevant medical illness \[renal, hepatic, cardiac, serious dermatological disorders such as exfoliative dermatitis, systemic lupus erythematosus (SLE)\] in the opinion of the investigators (see section 6.2a)
• Prior history of intolerance to any of the tetracyclines
• Concomitant penicillin therapy
• Concomitant anticoagulant therapy
• Presence of a seizure disorder, not including clozapine-induced seizures
• Presently taking valproic acid
• Any change of psychotropic medications within the previous six weeks
• Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria
• Pregnant or breast-feeding

Sponsors & Collaborators

• Stanley Medical Research Institute: lead
• Institute of Psychiatry, Rawalpindi Medical College, Pakistan: collaborator
• Pakistan Institute of Living and Learning: collaborator
• University of Sao Paulo: collaborator

Study Sites (4)

Department of Neurology, Psychiatry and Psychological Medicine, University of San Paulo

São Paulo, Brazil

Location

Civil Hospital Karachi

Karachi, Pakistan

Location

Karwan e Hayat

Karachi, Pakistan

Location

Institute of Psychiatry, Rawalpindi medical College

Rawalpindi, Pakistan

Location

Related Publications (6)

• Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. doi: 10.1038/77528.

  PMID: 10888929 BACKGROUND

• Gabrovska-Johnson VS, Scott M, Jeffries S, Thacker N, Baldwin RC, Burns A, Lewis SW, Deakin JF. Right-hemisphere encephalopathy in elderly subjects with schizophrenia: evidence from neuropsychological and brain imaging studies. Psychopharmacology (Berl). 2003 Sep;169(3-4):367-75. doi: 10.1007/s00213-003-1524-9. Epub 2003 Jul 4.

  PMID: 12845412 BACKGROUND

• Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500. doi: 10.1073/pnas.96.23.13496.

  PMID: 10557349 BACKGROUND

• Stirling J, White C, Lewis S, Hopkins R, Tantam D, Huddy A, Montague L. Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up of an epidemiological cohort. Schizophr Res. 2003 Dec 15;65(2-3):75-86. doi: 10.1016/s0920-9964(03)00014-8.

  PMID: 14630300 BACKGROUND

• Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, Sarang S, Liu AS, Hartley DM, Wu DC, Gullans S, Ferrante RJ, Przedborski S, Kristal BS, Friedlander RM. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002 May 2;417(6884):74-8. doi: 10.1038/417074a.

  PMID: 11986668 BACKGROUND

• Denovan-Wright EM, Devarajan S, Dursun SM, Robertson HA. Maintained improvement with minocycline of a patient with advanced Huntington's disease. J Psychopharmacol. 2002 Dec;16(4):393-4. doi: 10.1177/026988110201600417.

  PMID: 12503842 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Imran B Chaudhry, MD

  University of Manchester

  PRINCIPAL INVESTIGATOR

• Jaime EC Hallak, MD

  University of San Paulo, Brazil

  STUDY DIRECTOR

• Nusrat Husain, MD

  University of Manchester

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 8, 2009
• First Posted: June 9, 2009
• Study Start: May 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: June 15, 2009

Record last verified: 2009-06

Locations

BR (1); PA (3)