RCT of Methotrexate Added to Treatment As Usual in Schizophrenia

Phase 1

Completed

• Conditions: Schizoaffective Disorder; Schizophrenia; Schizophreniform Disorder
• Interventions: Drug: Methotrexate

• Registration Number: NCT02074319
• Lead Sponsor: Pakistan Institute of Living and Learning

Brief Summary

The aim of the this study is to evaluate the effectiveness of methotrexate added to treatment as usual on positive and negative symptoms, cognitive and social functioning and quality of life of patients suffering from schizophrenia.

Detailed Description

The purpose of the study is to test the prediction that addition of methotrexate to treatment as usual (TAU) for patients with schizophrenia will result in following outcomes:

* Primary:

* improvement in negative symptoms

* improvement in positive symptoms

* Secondary:

* improvement in social functioning

* improvement in cognitive functions

* acceptability and tolerability of methotrexate added to TAU A total 72 participants (36 participants in intervention group and 36 in control group) meeting inclusion criteria of the study will be recruited and randomized in study in two arms. Research assistants and participating psychiatrists will assess participants for eligibility criteria. After providing detailed information regarding study by using patient information sheet, written informed consent will be taken from participants. Trained research assistant will asses participants at baseline, 2, 4, 6 and 12 weeks.

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2014-02-26
• Study First Submitted QC: 2014-02-27
• Study First Posted: 2014-02-28
• Primary Completion: 2015-07
• Study Completion: 2015-08
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-19
• Last Update Posted: 2015-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

• Signed informed consent, indicating that the subject understood the purpose of and procedures required for the study, before the initiation of any study specific procedures

• Aged 18 to 35 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.

  1. Adequate contraception is defined as use of contraceptive double barrier system (i.e. condom and spermicide) or contraceptive implant, oral contraceptive or injected depot contraceptive plus other form of contraceptive i.e. condom. Females will be considered incapable of child bearing if they are one year post-menopausal or irreversibly surgically sterilised.

Exclusion Criteria

• Violation of any inclusion criteria
• Failure to perform screening or baseline examinations
• Relevant ICD 10 organic brain disease or neurological diagnoses
• Patients with liver disease
• Patients who will meet the criteria for a DSM-IV TR diagnosis of alcohol or substance abuse (other than for nicotine) within the last month or the criteria for DSM-IV TR alcohol or substance dependence (other than for nicotine) within the last 6 months
• Any change of psychotropic medications within the previous 4 weeks
• Recreational drugs or alcohol abuse
• Pregnant or lactating women and those of reproductive age without adequate contraception
• Relevant medical illness will be determined in the first instance by asking the patients mental health care team if the patient has any medical condition/problems. After consent has been obtained the research nurse/ research doctor will then have access to the patients' notes and will assess patient eligibility to take part in the clinical trial by scrutinising the patients' past medical history, most recent blood results, electrocardiograms, as well as any physical tests that have been performed on the patient.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methotrexate	Methotrexate	Methotrexate 10 mg once a week orally
Placebo	Methotrexate	Matching placebo for methotrexate

Primary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale PANSS	3 months	PANSS is an assessment measures to assess severity of symptoms of schizophrenia

Secondary Outcome Measures

Name	Time	Method
CogState	3 months	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 cognitions.

Trial Locations

Locations (4)

Civil hospital Karachi; 🇵🇰 Karachi, Sindh, Pakistan

Institute of Behavioural Sciences; 🇵🇰 Karachi, Sindh, Pakistan

Karwn e Hayat; 🇵🇰 Karachi, Sindh, Pakistan

Abasi Shaheed Hospital; 🇵🇰 Karachi, Sindh, Pakistan