SchizophreniaPhase 1RECOVERYNCT02074319
RCT of Methotrexate Added to Treatment As Usual in Schizophrenia
A Phase 1 study testing Methotrexate in people with Schizophrenia and Schizoaffective Disorder, run by Pakistan Institute of Living and Learning at 4 sites in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
- 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
- 92 participants
- Where
- 4 sitesPakistan
- Study dates
- Dec 2013to Aug 2015
- Phase
- Phase 1
- 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
- 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.
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- 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.
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
Pakistan4 sites
Abasi Shaheed Hospital
Karachi, Sindh, 72000
Civil hospital Karachi
Karachi, Sindh, 72000
Institute of Behavioural Sciences
Karachi, Sindh, 72000
Karwn e Hayat
Karachi, Sindh, 72000
About this study
Official title: A Randomised Double Blind Placebo Controlled 12 Week Trial of Methotrexate Added to Treatment As Usual in Early Schizophrenia
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.
Read the 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.
- Being tested
- Methotrexate
- Keywords
- Schizophrenia, Anti-Inflammatory, Methotrexate, Psychosis Not Otherwise Specified
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Treatment as usual or standard treatment for psychosis will be common in all arms
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matching placebo for methotrexate Receives: Drug: Methotrexate |
| Methotrexate | Experimental | Methotrexate 10 mg once a week orally Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positive and Negative Syndrome Scale PANSS
PANSS is an assessment measures to assess severity of symptoms of schizophrenia
Measured: 3 months
Secondary outcomes (1)
CogState
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2014 (estimated)
- Study startDec 2013
- Primary completionJul 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pakistan Institute of Living and Learning
- Sponsor type
- University, hospital or other
- Collaborators
- Abbasi Shaheed Hospital, Dow University of Health Sciences, Karwan e Hayat, Karachi, Pakistan, Institute of Behavioural Sciences, Karachi, Pakistan
- Responsible party
- Sponsor
- Investigators
- Prof Imran B Chaudhry, MD, Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02074319
- Sponsor's protocol ID
- RECOVERY-001
- Acronym
- RECOVERY
- Status last verified
- Sep 2015
- First submitted
- 26 Feb 2014
- Last updated
- 22 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941. Epub 2012 Apr 23.
PubMed 22526685Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci. 2008 Dec 17;28(51):13957-66. doi: 10.1523/JNEUROSCI.4457-08.2008.
PubMed 19091984Bernstein HG, Steiner J, Bogerts B. Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy. Expert Rev Neurother. 2009 Jul;9(7):1059-71. doi: 10.1586/ern.09.59.
PubMed 19589054Busse S, Busse M, Schiltz K, Bielau H, Gos T, Brisch R, Mawrin C, Schmitt A, Jordan W, Muller UJ, Bernstein HG, Bogerts B, Steiner J. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations? Brain Behav Immun. 2012 Nov;26(8):1273-9. doi: 10.1016/j.bbi.2012.08.005. Epub 2012 Aug 14.
PubMed 22917959Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005 Jun;57(2):163-72. doi: 10.1124/pr.57.2.3.
PubMed 15914465Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009 Nov;50(11):1801-7. doi: 10.2967/jnumed.109.066647. Epub 2009 Oct 16.
PubMed 19837763Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS. Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006 Nov;20(6):532-45. doi: 10.1016/j.bbi.2006.02.002. Epub 2006 Apr 3.
PubMed 16580814Godfrey PS, Toone BK, Carney MW, Flynn TG, Bottiglieri T, Laundy M, Chanarin I, Reynolds EH. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. 1990 Aug 18;336(8712):392-5. doi: 10.1016/0140-6736(90)91942-4.
PubMed 1974941Gong K, Zhang Z, Sun X, Zhang X, Li A, Yan J, Luo Q, Gao Y, Feng Y. The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure. Am Heart J. 2006 Jan;151(1):62-8. doi: 10.1016/j.ahj.2005.02.040.
PubMed 16368293Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. doi: 10.1016/j.clim.2004.09.001.
PubMed 15639649Mansur RB, Zugman A, Asevedo EM, da Cunha GR, Bressan RA, Brietzke E. Cytokines in schizophrenia: possible role of anti-inflammatory medications in clinical and preclinical stages. Psychiatry Clin Neurosci. 2012 Jun;66(4):247-60. doi: 10.1111/j.1440-1819.2012.02354.x.
PubMed 22624729Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011 Oct 1;70(7):663-71. doi: 10.1016/j.biopsych.2011.04.013. Epub 2011 Jun 8.
PubMed 21641581Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257-65. doi: 10.1111/j.1440-1819.2009.01945.x.
PubMed 19579286Morgan SL, Baggott JE, Vaughn WH, Austin JS, Veitch TA, Lee JY, Koopman WJ, Krumdieck CL, Alarcon GS. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994 Dec 1;121(11):833-41. doi: 10.7326/0003-4819-121-11-199412010-00002.
PubMed 7978695Myint AM. Kynurenines: from the perspective of major psychiatric disorders. FEBS J. 2012 Apr;279(8):1375-85. doi: 10.1111/j.1742-4658.2012.08551.x. Epub 2012 Mar 27.
PubMed 22404766
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Double Blind Placebo Controlled 12 Week Trial of Methotrexate Added to Treatment As Usual in Early Schizophrenia
- ClinicalTrials.gov ID
- NCT02074319
- Acronym / sponsor ID
- RECOVERY / RECOVERY-001
- Keywords
- Schizophrenia, Anti-Inflammatory, Methotrexate, Psychosis Not Otherwise Specified
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Pakistan Institute of Living and LearningUniversity, hospital or other
- Collaborators
- Abbasi Shaheed Hospital, Dow University of Health Sciences, Karwan e Hayat, Karachi, Pakistan, Institute of Behavioural Sciences, Karachi, Pakistan
- Study start
- Dec 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 28 Feb 2014 (estimated)
- 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.
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 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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: MethotrexateMatching placebo for methotrexate |
| Methotrexate | Experimental | Drug: MethotrexateMethotrexate 10 mg once a week orally |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| MethotrexateTreatment as usual or standard treatment for psychosis will be common in all arms | Drug | Methotrexate, Placebo |
Primary outcome
Positive and Negative Syndrome Scale PANSS
Time frame: 3 months
PANSS is an assessment measures to assess severity of symptoms of schizophrenia
1 secondary outcome
CogState
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2015.
- Background: PubMed 22526685Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941. Epub 2012 Apr 23.
- Background: PubMed 19091984Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci. 2008 Dec 17;28(51):13957-66. doi: 10.1523/JNEUROSCI.4457-08.2008.
- Background: PubMed 19589054Bernstein HG, Steiner J, Bogerts B. Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy. Expert Rev Neurother. 2009 Jul;9(7):1059-71. doi: 10.1586/ern.09.59.
- Background: PubMed 22917959Busse S, Busse M, Schiltz K, Bielau H, Gos T, Brisch R, Mawrin C, Schmitt A, Jordan W, Muller UJ, Bernstein HG, Bogerts B, Steiner J. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations? Brain Behav Immun. 2012 Nov;26(8):1273-9. doi: 10.1016/j.bbi.2012.08.005. Epub 2012 Aug 14.
- Background: PubMed 15914465Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005 Jun;57(2):163-72. doi: 10.1124/pr.57.2.3.
- Background: PubMed 19837763Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med. 2009 Nov;50(11):1801-7. doi: 10.2967/jnumed.109.066647. Epub 2009 Oct 16.
- Background: PubMed 16580814Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS. Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006 Nov;20(6):532-45. doi: 10.1016/j.bbi.2006.02.002. Epub 2006 Apr 3.
- Background: PubMed 1974941Godfrey PS, Toone BK, Carney MW, Flynn TG, Bottiglieri T, Laundy M, Chanarin I, Reynolds EH. Enhancement of recovery from psychiatric illness by methylfolate. Lancet. 1990 Aug 18;336(8712):392-5. doi: 10.1016/0140-6736(90)91942-4.
- Background: PubMed 16368293Gong K, Zhang Z, Sun X, Zhang X, Li A, Yan J, Luo Q, Gao Y, Feng Y. The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure. Am Heart J. 2006 Jan;151(1):62-8. doi: 10.1016/j.ahj.2005.02.040.
- Background: PubMed 15639649Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. doi: 10.1016/j.clim.2004.09.001.
- Background: PubMed 22624729Mansur RB, Zugman A, Asevedo EM, da Cunha GR, Bressan RA, Brietzke E. Cytokines in schizophrenia: possible role of anti-inflammatory medications in clinical and preclinical stages. Psychiatry Clin Neurosci. 2012 Jun;66(4):247-60. doi: 10.1111/j.1440-1819.2012.02354.x.
- Background: PubMed 21641581Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011 Oct 1;70(7):663-71. doi: 10.1016/j.biopsych.2011.04.013. Epub 2011 Jun 8.
- Website of Pakistan Institute of Learning and LivingLink provided by the sponsor.
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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.
Prof Imran B Chaudhry, MD principal investigator
University of Manchester
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methotrexate in people with Schizophrenia and Schizoaffective Disorder, run by Pakistan Institute of Living and Learning at 4 sites in Pakistan.
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 9 inclusion and 9 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: finished, as of the sponsor's last update on 22 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positive and Negative Syndrome Scale PANSS (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02074319, which also lists 23 linked publications.
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 22 Sep 2015.