Add-on Methotrexate for the Treatment of Schizophrenia
Ključne besede
Povzetek
Opis
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.
Datumi
| Nazadnje preverjeno: | 11/30/2017 |
| Prvič predloženo: | 12/02/2017 |
| Predviden vpis oddan: | 12/09/2017 |
| Prvič objavljeno: | 12/11/2017 |
| Zadnja posodobitev oddana: | 12/09/2017 |
| Zadnja posodobitev objavljena: | 12/11/2017 |
| Dejanski datum začetka študija: | 12/14/2017 |
| Predvideni datum primarnega zaključka: | 12/31/2019 |
| Predvideni datum zaključka študije: | 12/31/2019 |
Stanje ali bolezen
Intervencija / zdravljenje
Drug: Study Drug
Other: Placebo
Faza
Skupine rok
| Roka | Intervencija / zdravljenje |
|---|---|
| Experimental: Study Drug Methotrexate 10mg | Drug: 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 Comparator: Placebo Pills equivalent to other study arm (10 mg) | Other: 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. |
Merila upravičenosti
| Starost, primerna za študij | 18 Years Za 18 Years |
| Spol, upravičen do študija | All |
| Sprejema zdrave prostovoljce | Da |
| Merila | 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 |
Izid
Primarni izidni ukrepi
1. PANSS (Positive and Negative Syndrome Scale) Positive Subscale Score at the end of the trial [Changes throughout 16 weeks]
Ukrepi sekundarnega rezultata
1. PANSS (Positive and Negative Syndrome Scale) Total score at the end of the trial [Changes throughout 16 weeks]
2. PANSS (Positive and Negative Syndrome Scale) Negative Susbcale Score at the end of the trial [Changes throughout 16 weeks]
3. PANSS (Positive and Negative Syndrome Scale) General Psychopathology Subscale Score at the end of the trial [Changes throughout 16 weeks]
4. Clinical Global Impression Scale- Severity (CGI-S) at the end of the trial [Changes throughout 16 weeks]
5. Clinical Global Impression Scale- Improvement (CGI-I) at the end of the trial [Changes throughout 16 weeks]
6. Social Functioning Scale Assessment (PSP) at the end of the trial [Changes throughout 16 weeks]
7. Rates of drop outs before the end of the trial [Rates throughout 16 weeks]
