SchizophreniaPhase 2NCT03369795
Add-on Methotrexate for the Treatment of Schizophrenia
A Phase 2 study testing Methotrexate in people with Schizophrenia, run by Sheba Medical Center.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 15 Dec 2017to 1 Jan 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Randomized Double Blind Parallel Trial Administering Methotrexate vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffecive Disorder
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.
Read the detailed description
OBJECTIVES The objective of the study is to evaluate the efficacy of Methotrexate compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia or schizoaffective disorder.
ENDPOINTS Primary outcome measure: PANSS positive score at the end of the trial. Secondary outcome measures: PANSS total, negative and general psychopathology scales, Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I), Social Functioning Scale Assessment (PSP) and rates of drop outs before the end of the trial.
DESIGN Randomized, add-on to anti-psychotics, double blind, placebo-controlled trial.
ASSESSMENTS
- Positive and Negative Syndrome Scale (PANSS). PANSS is a 30-item rating scale widely used in assessment of medication effects in schizophrenia.
- Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I). CGI-S and CGI-I will be used to assess severity of the illness and global improvement.
- The Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale: will be used to assess commonly occurring side effects caused by anti-psychotics.
- The methotrexate toxicity checklist includes rash, oral ulceration, nausea and vomiting, diarrhea, new or increasing dyspnea, new or increasing dry cough, severe sore throat, and abnormal bruising.
- The Personal and Social Performance (PSP) scale will be used to assess social functioning.
PROCEDURE At the screening visit informed consent will be obtained, inclusion and exclusion criteria will be examined, and demographic information will be collected. The PANSS, CGI-S and SCID assessment will be administered, a physical examination will be done, psychiatric and medical history obtained, and blood samples for chemistry and CBC, and urine samples for urinalysis will be taken. Patients will liver function levels higher than normal will be excluded. Females of child-bearing potential will be tested for pregnancy. Patients will be screened for HIV, Hepatitis B and C.
At the baseline visit, The PANSS, CGI-S, UKU, and PSP will be administered. Patients will be randomized to start study medication: Methotrexate 10 mg/week or equivalent dose of placebo will be administered to patients. Medication dose will start at 10mg for the first two weeks and will then be increased to 15 mg. Patients will also be instructed to take 5 mg/day of folic acid for 6 days/week in order to avoid vitamin deficiencies due to the methotrexate use. In order to monitor potential side-effects, blood tests for CBC and SMA will be taken at screening, week 2, week 4, week 8, week 12, and week 16 (EOS).
Subjects will be assessed at clinic visits according to timelines described above. Additionally, during the weeks in which patients will not come for clinic visits, they will have phone visits in order to monitor medication adherence and adverse events. Throughout all the visits between baseline and end of study, patients will be checked for methotrexate toxicity using the methotrexate toxicity checklist which inquires for includes rash, oral ulceration, nausea and vomiting, diarrhea, new or increasing dyspnea, new or increasing dry cough, severe sore throat, and abnormal bruising.
A final, End-of-Study, clinical evaluation will occur on Week 16, or at the time of early discontinuation from the study, and will include a physical examination; vital signs; rating of the PANSS, CGI-S, CGI-I, UKU, PSP, review of adverse events, methotrexate toxicity checklist and concomitant medications. Blood samples will be taken for SMA, CBC, and urine samples for urinalysis. Females of child-bearing potential will be tested for pregnancy, and a blood sample for medication levels will be taken.
- Conditions
- Schizophrenia
- Being tested
- Methotrexate, Placebo Arm
- Keywords
- methotrexate, add-on, schizophrenia, schizoaffective
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Also called Study 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.
Placebo ArmOther
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| Study Drug | Experimental | Methotrexate 10mg Receives: Drug: Methotrexate |
| Placebo | Placebo comparator | Pills equivalent to other study arm (10 mg) Receives: Other: Placebo Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Changes throughout 16 weeks
Secondary outcomes (7)
PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial
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
Measured: Changes throughout 16 weeks
PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial
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
Measured: Changes throughout 16 weeks
PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial
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
Measured: Changes throughout 16 weeks
Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial
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)
Measured: Changes throughout 16 weeks
Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial
This is a clinical scale with a minimum score of 1 (very much improved) and a maximum score of 7 (very much worse)
Measured: Changes throughout 16 weeks
Social Functioning Scale Assessment (PSP) at the end of the trial
This is a social functioning scale with a minimum score of 1 (no functioning) and a maximum score of 100 (excellent functioning)
Measured: Changes throughout 16 weeks
Rates of drop outs before the end of the trial
The number of drop outs from the study will be analysed at the end of the study.
Measured: Rates throughout 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2017
- Study start15 Dec 2017 (estimated)
- Primary completion1 Jan 2020 (estimated)
- Study completion1 Jan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03369795
- Sponsor's protocol ID
- SHEBA-17-3512-MW-CTIL
- Status last verified
- Dec 2017
- First submitted
- 3 Dec 2017
- Last updated
- 12 Dec 2017
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Parallel Trial Administering Methotrexate vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffecive Disorder
- ClinicalTrials.gov ID
- NCT03369795
- Acronym / sponsor ID
- SHEBA-17-3512-MW-CTIL
- Conditions
- Schizophrenia
- Keywords
- methotrexate, add-on, schizophrenia, schizoaffective
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 15 Dec 2017 (estimated)
- Primary completion
- 1 Jan 2020 (estimated)
- Study completion
- 1 Jan 2020 (estimated)
- First posted
- 12 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES The objective of the study is to evaluate the efficacy of Methotrexate compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia or schizoaffective disorder.
ENDPOINTS Primary outcome measure: PANSS positive score at the end of the trial. Secondary outcome measures: PANSS total, negative and general psychopathology scales, Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I), Social Functioning Scale Assessment (PSP) and rates of drop outs before the end of the trial.
DESIGN Randomized, add-on to anti-psychotics, double blind, placebo-controlled trial.
ASSESSMENTS
- Positive and Negative Syndrome Scale (PANSS). PANSS is a 30-item rating scale widely used in assessment of medication effects in schizophrenia.
- Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I). CGI-S and CGI-I will be used to assess severity of the illness and global improvement.
- The Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale: will be used to assess commonly occurring side effects caused by anti-psychotics.
- The methotrexate toxicity checklist includes rash, oral ulceration, nausea and vomiting, diarrhea, new or increasing dyspnea, new or increasing dry cough, severe sore throat, and abnormal bruising.
- The Personal and Social Performance (PSP) scale will be used to assess social functioning.
PROCEDURE At the screening visit informed consent will be obtained, inclusion and exclusion criteria will be examined, and demographic information will be collected. The PANSS, CGI-S and SCID assessment will be administered, a physical examination will be done, psychiatric and medical history obtained, and blood samples for chemistry and CBC, and urine samples for urinalysis will be taken. Patients will liver function levels higher than normal will be excluded. Females of child-bearing potential will be tested for pregnancy. Patients will be screened for HIV, Hepatitis B and C.
At the baseline visit, The PANSS, CGI-S, UKU, and PSP will be administered. Patients will be randomized to start study medication: Methotrexate 10 mg/week or equivalent dose of placebo will be administered to patients. Medication dose will start at 10mg for the first two weeks and will then be increased to 15 mg. Patients will also be instructed to take 5 mg/day of folic acid for 6 days/week in order to avoid vitamin deficiencies due to the methotrexate use. In order to monitor potential side-effects, blood tests for CBC and SMA will be taken at screening, week 2, week 4, week 8, week 12, and week 16 (EOS).
Subjects will be assessed at clinic visits according to timelines described above. Additionally, during the weeks in which patients will not come for clinic visits, they will have phone visits in order to monitor medication adherence and adverse events. Throughout all the visits between baseline and end of study, patients will be checked for methotrexate toxicity using the methotrexate toxicity checklist which inquires for includes rash, oral ulceration, nausea and vomiting, diarrhea, new or increasing dyspnea, new or increasing dry cough, severe sore throat, and abnormal bruising.
A final, End-of-Study, clinical evaluation will occur on Week 16, or at the time of early discontinuation from the study, and will include a physical examination; vital signs; rating of the PANSS, CGI-S, CGI-I, UKU, PSP, review of adverse events, methotrexate toxicity checklist and concomitant medications. Blood samples will be taken for SMA, CBC, and urine samples for urinalysis. Females of child-bearing potential will be tested for pregnancy, and a blood sample for medication levels will be taken.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Drug | Experimental | Drug: MethotrexateMethotrexate 10mg |
| Placebo | Placebo comparator | Other: Placebo ArmPills equivalent to other study arm (10 mg) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateAlso: Study DrugMethotrexate 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. | Drug | Study Drug |
| Placebo ArmAlso: PlaceboPills 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 | Placebo |
Primary outcome
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
7 secondary outcomes
PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial
Time frame: Changes throughout 16 weeks
PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial
Time frame: Changes throughout 16 weeks
PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial
Time frame: Changes throughout 16 weeks
Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial
Time frame: Changes throughout 16 weeks
Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial
Time frame: Changes throughout 16 weeks
Social Functioning Scale Assessment (PSP) at the end of the trial
Time frame: Changes throughout 16 weeks
Rates of drop outs before the end of the trial
Time frame: Rates throughout 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methotrexate in people with Schizophrenia, run by Sheba Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mark Weiser, MD (+97235303773, mweiser@netvision.net.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial (time frame: Changes throughout 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2017.