ClinicalTrials.gov
ClinicalTrials.gov Menu

Add-on Methotrexate for the Treatment of Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03369795
Recruitment Status : Not yet recruiting
First Posted : December 12, 2017
Last Update Posted : December 12, 2017
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center

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.


Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Methotrexate Other: Placebo Arm Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double Blind Parallel Trial Administering Methotrexate vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffecive Disorder
Estimated Study Start Date : December 15, 2017
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : January 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: Study Drug
Methotrexate 10mg
Drug: Methotrexate
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.
Other Name: Study Drug

Placebo Comparator: Placebo
Pills equivalent to other study arm (10 mg)
Other: Placebo Arm
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.
Other Name: Placebo




Primary Outcome Measures :
  1. PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    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


Secondary Outcome Measures :
  1. PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    The PANSS scale has a minimum score of 30 and a maximum score of 210, 30 showing no symptomatology, and 210 showing very severe symptomatology

  2. PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    The negative score subscale has a minimum score of 7 and a maximum score of 49, 7 showing no symptomatology, and 49 showing very severe symptomatology

  3. PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    The general psychopathology subscale score has a minimum score of 16 and a maximum score of 112, 16 showing no symptomatology, and 112 showing very severe symptomatology

  4. Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    This is a clinical scale with a minimum score of 1 (not ill) and a maximum score of 7 (among the most extremely ill patients)

  5. Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    This is a clinical scale with a minimum score of 1 (very much improved) and a maximum score of 7 (very much worse)

  6. Social Functioning Scale Assessment (PSP) at the end of the trial [ Time Frame: Changes throughout 16 weeks ]
    This is a social functioning scale with a minimum score of 1 (no functioning) and a maximum score of 100 (excellent functioning)

  7. Rates of drop outs before the end of the trial [ Time Frame: Rates throughout 16 weeks ]
    The number of drop outs from the study will be analysed at the end of the study.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18-35 years of age, inclusive
  2. 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]).
  3. Willing and able to provide informed consent, after the nature of the study has been fully explained.
  4. Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified SCID.
  5. Within the first five years of diagnosis.
  6. 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.
  7. Receiving only one anti-psychotic within PORT dosages
  8. Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission

Exclusion Criteria:

  1. Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
  2. Evidence of significant liver disease. Patients with LFT above normal will be excluded.
  3. Pregnant or breast-feeding
  4. 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)
  5. At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
  6. 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.
  7. Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
  8. Lactose intolerance
  9. Immune system disorder or serious infection
  10. Patients taking Clozapine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03369795


Contacts
Contact: Mark Weiser, MD +97235303773 mweiser@netvision.net.il
Contact: Linda Levi +97235303773 lindalevi90@gmail.com

Sponsors and Collaborators
Sheba Medical Center

Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT03369795     History of Changes
Other Study ID Numbers: SHEBA-17-3512-MW-CTIL
First Posted: December 12, 2017    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sheba Medical Center:
methotrexate
add-on
schizophrenia
schizoaffective

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors