Allopurinol in Schizophrenia: A Randomized Trial Administering Allopurinol vs Placebo as add-on Antipsychotics in Patients With Schizophrenia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00864825
First received: March 17, 2009
Last updated: May 6, 2012
Last verified: May 2012
  Purpose

The objective of the study is to evaluate the efficacy of allopurinol, compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Allopurinol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Allopurinol in Schizophrenia: A Randomized Trial Administering Allopurinol vs Placebo as add-on Antipsychotics in Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • PANSS total score. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PANSS positive, negative and general psychopathology scales, BACS, CGI, Simpson-Angus Scale. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 248
Study Start Date: August 2009
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allopurinol Drug: Allopurinol
Allopurinol 1 capsule 300 mg, or placebo, bid (twice a day) for 42 days.
Other Name: Alloril, Zylol, Zyloric
Placebo Comparator: Placebo Drug: Allopurinol
Allopurinol 1 capsule 300 mg, or placebo, bid (twice a day) for 42 days.
Other Name: Alloril, Zylol, Zyloric

Detailed Description:

An emerging body of evidence supports a purinergic hypothesis for schizophrenia. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists and there is a well characterized antagonistic interaction between adenosine and dopamine receptors in the ventral striatum1. Increased adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. It has been theorized that adenosine may exert some of its antipsychotic effects through modulation of glutamatergic transmission.

Three double-blind, randomized, placebo-controlled trials have showed statistically significant greater improvements in PANSS scores in the allopurinol groups vs. placebo groups. These empiric data, together with the theoretical and basic science background cited, provide the impetus for this proposed study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18-65 years of age, inclusive
  2. Because gout is relatively rare in women of childbearing age, there are few reports describing the use of allopurinol during pregnancy; in those there were no adverse fetal outcomes attributable to allopurinol. Therefore, only 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]) can be included in the trial.
  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 as confirmed by SCID
  5. Symptoms: 4 (moderate) or above on CGI-S AND >= 4 (moderate) score on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution.
  6. Must be on any antipsychotic drug for at least 2 weeks prior to the baseline visit, at doses within the PORT criteria. Patients receiving higher doses will have their records reviewed to insure that dose is required. Patients receiving two anti-psychotics, or IM depot antipsychotics can also be included.
  7. Inpatients or outpatients.

Exclusion Criteria:

  1. Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
  2. Pregnant or breast-feeding
  3. Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, , kidney disease, impaired liver functioning
  4. Likely allergy or sensitivity to allopurinol
  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. Suffers from a significant Substance Dependence disorder based on DSM-IV criteria within the 3 months prior to Screening, or is deemed by the Investigator to have a high risk of substance use during the study. Patients with a history of 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 brain trauma.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00864825

Locations
Israel
Abrabanel Mental Health Center
Bat Yam, Israel, 59436
Beer-Yaakov Mental Health Center
Beer-Yaakov, Israel, 70350
Shalvata Mental Health Center
Hod Hasharon, Israel
Jaffa Mental House Center
Jaffa, Israel, 66849
Herzog Medical Center, Psychiatry
Jerusalem, Israel, 91351
Kfar Shaul Mental Health Center
Jerusalem, Israel
Nes Ziona Mental Health Center
Nes Ziona, Israel
Shaar Menashe Mental Health Center
Shaar Menashe, Israel, 38814
Sheba Medical Center, Psychiatry Department
Tel Hashomer, Ramat Gan, Israel
Lev Hasharon Mental Health Center
Zur-Moshe, Israel
Romania
Spitalul Clinic de Urgenta Clinica "E. Pamfil" Timisoara
Bd. Iosif Bulbuca, 156, jud timis, Romania
Spitalul Clinic de Psihiatrie, sectia 14
Berceni st., 10-12, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 10
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul clinic de Psihiatrie, sectia 13
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 6
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 1
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 12
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 3
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, Clinica 9
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic, sectia 8
Berceni st., sector 4 Bucharest, Romania, 041902
Spitalul de Psihiatrie, Titan
Bld Nicolae Grigorescu, no. 41, Sector 3,, Romania
Spitalul Clinic de Urgenta Militar Sectia Psihiatrie Clinica
Bucuresti, Mircea Vulcanescu 88, Str. Vulcanescu, Nr. 88, Romania
Spitalul de Neuropsihiatrie Oradea
Cuza Voda st, 36, Oradea, Romania, 410097
Clinica de Psihiatrie nr.1
Gh. Marinescu st.38 ,Targu-Mures, Romania, 540139
Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
Octavian Goga st, 17, Arad, Romania, 310022
Spitalul Clinic de Psihiatrie "Socola"
Sos Bucium, 36, Iasi, Romania, 700282
Spitalul Clinic Colentina Cabinet Psihiatrie Ambulatoriu
Sos. Stefan Cel Mare Nr. 19-21, sect. 2, Romania
Spitalul Clinic de Psihiatrie "Ghe. Preda"
Str. Bagdazar 12, Sibiu, Romania, 550245
Spitalul Clinic Judetean de Urgenta -Cluj
Str. Clinicilor nr. 3-5, 3400, Romania
Spitalul de Psihiatrie Botosani
Str. I.C.Bratianu Nr. 116, Botosani, Romania
Spitalul Clinic de Psihiatrie si Neurologie
Str. Prundului 7 - 9, Brasov, Romania, 500123
Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
Str. Victor Babes, nr. 43, Cluj Napoca, Romania, 400012
Spitalul de Psihiatrie si Neurologie
Str.Mihai Eminescu, Nr.18, Brasov, Romania, 500079
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Mark Weiser, MD Sheba Medical Center
  More Information

No publications provided by Sheba Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00864825     History of Changes
Other Study ID Numbers: SHEBA-09-6893-MW-CTIL
Study First Received: March 17, 2009
Last Updated: May 6, 2012
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
Schizophrenia
Allopurinol
Add-on-treatment

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Allopurinol
Antipsychotic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 28, 2014