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

Phase 4

Completed

• Conditions: Schizophrenia; Schizoaffective Disorder
• Interventions: Drug: Allopurinol

• Registration Number: NCT00864825
• Lead Sponsor: Sheba Medical Center

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2009-03-17
• Study First Submitted QC: 2009-03-18
• Study First Posted: 2009-03-19
• Study Start: 2009-08
• Primary Completion: 2009-12
• Study Completion: 2010-01
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-06
• Last Update Posted: 2012-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 248

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allopurinol	Allopurinol	-
Placebo	Allopurinol	-

Primary Outcome Measures

Name	Time	Method
PANSS total score.	6 weeks

Secondary Outcome Measures

Name	Time	Method
PANSS positive, negative and general psychopathology scales, BACS, CGI, Simpson-Angus Scale.	6 weeks

Trial Locations

Locations (33)

Sheba Medical Center, Psychiatry Department; 🇮🇱 Tel Hashomer, Ramat Gan, Israel

Spitalul Clinic, sectia 8; 🇷🇴 Berceni st., sector 4 Bucharest, Romania

Spitalul Clinic de Urgenta Clinica "E. Pamfil" Timisoara; 🇷🇴 Bd. Iosif Bulbuca, 156, jud timis, Romania

Shalvata Mental Health Center; 🇮🇱 Hod Hasharon, Israel

Jaffa Mental House Center; 🇮🇱 Jaffa, Israel

Beer-Yaakov Mental Health Center; 🇮🇱 Beer-Yaakov, Israel

Herzog Medical Center, Psychiatry; 🇮🇱 Jerusalem, Israel

Shaar Menashe Mental Health Center; 🇮🇱 Shaar Menashe, Israel

Nes Ziona Mental Health Center; 🇮🇱 Nes Ziona, Israel

Lev Hasharon Mental Health Center; 🇮🇱 Zur-Moshe, Israel

Spitalul clinic de Psihiatrie, sectia 13; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul de Neuropsihiatrie Oradea; 🇷🇴 Cuza Voda st, 36, Oradea, 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

Spitalul de Psihiatrie si Neurologie; 🇷🇴 Str.Mihai Eminescu, Nr.18, Brasov, Romania

Kfar Shaul Mental Health Center; 🇮🇱 Jerusalem, Israel

Abrabanel Mental Health Center; 🇮🇱 Bat Yam, Israel

Spitalul Clinic de Psihiatrie, sectia 1; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul Clinic de Psihiatrie "Socola"; 🇷🇴 Sos Bucium, 36, Iasi, Romania

Spitalul Clinic Judetean de Urgenta -Cluj; 🇷🇴 Str. Clinicilor nr. 3-5, 3400, Romania

Spitalul Clinic de Psihiatrie, Clinica 9; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul Clinic de Psihiatrie, sectia 3; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Clinica de Psihiatrie nr.1; 🇷🇴 Gh. Marinescu st.38 ,Targu-Mures, Romania

Spitalul Clinic de Psihiatrie, sectia 14; 🇷🇴 Berceni st., 10-12, Bucharest, Romania

Spitalul Clinic de Urgenta Militar Sectia Psihiatrie Clinica; 🇷🇴 Bucuresti, Mircea Vulcanescu 88, Str. Vulcanescu, Nr. 88, Romania

Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie; 🇷🇴 Octavian Goga st, 17, Arad, Romania

Spitalul Clinic de Psihiatrie, sectia 10; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul Clinic de Psihiatrie, sectia 12; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul Clinic de Psihiatrie, sectia 6; 🇷🇴 Berceni st., 10-12, sector 4, Bucharest, Romania

Spitalul de Psihiatrie, Titan; 🇷🇴 Bld Nicolae Grigorescu, no. 41, Sector 3,, Romania

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

Spitalul Clinic Judetean, Sectia Clinica Psihiatrie; 🇷🇴 Str. Victor Babes, nr. 43, Cluj Napoca, Romania