Add-on Methotrexate for the Treatment of Schizophrenia

NCT03369795 | Unknown Phase 2

• 1 other identifier: SHEBA-17-3512-MW-CTIL
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

A recent double-blind placebo-controlled study has tested the effect of methotrexate as an add-on treatment for patients with schizophrenia or schizoaffective disorder, administering 10 mg of methotrexate or placebo once a week for a period of three months to 72 patients (Chaudry, Husain et al. 2015). Results showed improvement both in positive symptoms, as measured by the Positive symptoms subscale of the Positive and Negative Syndrome Scale (PANSS), and in total PANSS scores. The objective of this study is to replicate Chaudry et al.'s study. This proposed study will randomize schizophrenia or schizoaffective disorder patients to methotrexate or placebo for a period of four months. The study will enroll patients with a DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder confirmed by the Modified Structured Clinical Interview for Diagnosis (SCID). In order to be eligible to enter the study, the patient must have a score of 4 (moderately ill) or greater on the Clinical Global Impression - Severity (CGI-S) scale. In addition, inclusion criteria reflect patients with moderate or more severity on positive symptoms, hence having a score of 4 (moderate) or above on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution. Patients receiving more than one anti-psychotic or depot antipsychotic will be allowed to participate, and patients receiving anti-cholinergic agents, beta-blockers, anti-depressants, mood-stabilizers, sedatives, and anti-anxiety agents will be allowed in the study. Because the clinical status of patients sometimes improves in the days following admission to the hospital, newly hospitalized patients will have their baseline visit 3 days or more after being hospitalized.

Conditions

Schizophrenia

Keywords

methotrexate; add-on; schizophrenia; schizoaffective

Outcome Measures

Primary Outcomes (1)

• PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial

  The positive score subscale has a minimum score of 7 and a maximum score of 49, 7 showing no symptomatology, and 49 showing very severe symptomatology

  Changes throughout 16 weeks

Secondary Outcomes (7)

• PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial

  Changes throughout 16 weeks

• PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial

  Changes throughout 16 weeks

• PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial

  Changes throughout 16 weeks

• Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial

  Changes throughout 16 weeks

• Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial

  Changes throughout 16 weeks

Study Arms (2)

Study Drug

EXPERIMENTAL

Methotrexate 10mg

Drug: Methotrexate

Placebo

PLACEBO COMPARATOR

Pills equivalent to other study arm (10 mg)

Other: Placebo Arm

Interventions

Methotrexate DRUG

Methotrexate 10mg once a week will be given for the first two weeks of the trial, followed by an increase in dose to 15mg or equivalent placebo once a week until week 16.

Also known as: Study Drug

Study Drug

Placebo Arm OTHER

Pills equivalent to the study drug arm (10mg) will be given once a week for the first two weeks of the trial, followed by an increase in dose to 15mg of equivalent placebo once a week until week 16.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, 18-35 years of age, inclusive
• Females who are abstinent or practicing an established method of birth control (oral contraceptive tablets, hormonal implant device, hormone patch, injectable contraceptive, intrauterine device \[IUD\]).
• Willing and able to provide informed consent, after the nature of the study has been fully explained.
• Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified SCID.
• Within the first five years of diagnosis.
• Positive symptoms: 4 (moderate) or above on CGI-S and a score of 4 (moderate) or above on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution.
• Receiving only one anti-psychotic within PORT dosages
• Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission

You may not qualify if:

• Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
• Evidence of significant liver disease. Patients with LFT above normal will be excluded.
• Pregnant or breast-feeding
• Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, COPD and other chronic lungs diseases, serious hematological disorder, kidney disease, impaired liver functioning)
• At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
• Patients with a current DSM-IV substance or alcohol abuse. Patients with a history of and/or current recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
• Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
• Lactose intolerance
• Immune system disorder or serious infection
• Patients taking Clozapine

Sponsors & Collaborators

• Sheba Medical Center: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

Methotrexate; Drug Evaluation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Central Study Contacts

Mark Weiser, MD

CONTACT

+97235303773; mweiser@netvision.net.il

Linda Levi

CONTACT

+97235303773; lindalevi90@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2017
• First Posted: December 12, 2017
• Study Start: December 15, 2017
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: December 12, 2017

Record last verified: 2017-12