Clinical trial NCT00864825: Allopurinol in Schizophrenia: A Randomized Trial Administering Allopurinol vs Placebo as add-on Antipsychotics in Patients With Schizophrenia
Official title: Allopurinol in Schizophrenia: A Randomized Trial Administering Allopurinol vs Placebo as add-on Antipsychotics in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: Schizophrenia
Allopurinol
Add-on-treatment
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2009-03-19
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: PANSS total score.
timeFrame: 6 weeks
Secondary outcomes:
measure: PANSS positive, negative and general psychopathology scales, BACS, CGI, Simpson-Angus Scale.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Bat Yam
country: Israel
facility: Abrabanel Mental Health Center
city: Beer-Yaakov
country: Israel
facility: Beer-Yaakov Mental Health Center
city: Hod Hasharon
country: Israel
facility: Shalvata Mental Health Center
city: Jaffa
country: Israel
facility: Jaffa Mental House Center
city: Jerusalem
country: Israel
facility: Herzog Medical Center, Psychiatry
city: Jerusalem
country: Israel
facility: Kfar Shaul Mental Health Center
city: Nes Ziona
country: Israel
facility: Nes Ziona Mental Health Center
city: Shaar Menashe
country: Israel
facility: Shaar Menashe Mental Health Center
city: Tel Hashomer, Ramat Gan
country: Israel
facility: Sheba Medical Center, Psychiatry Department
city: Zur-Moshe
country: Israel
facility: Lev Hasharon Mental Health Center
city: Bd. Iosif Bulbuca, 156, jud timis
country: Romania
facility: Spitalul Clinic de Urgenta Clinica "E. Pamfil" Timisoara
city: Berceni st., 10-12, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 14
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, Clinica 9
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 10
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 12
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul clinic de Psihiatrie, sectia 13
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 1
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 3
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 6
city: Berceni st., sector 4 Bucharest
country: Romania
facility: Spitalul Clinic, sectia 8
city: Bld Nicolae Grigorescu, no. 41, Sector 3,
country: Romania
facility: Spitalul de Psihiatrie, Titan
city: Bucuresti, Mircea Vulcanescu 88, Str. Vulcanescu, Nr. 88
country: Romania
facility: Spitalul Clinic de Urgenta Militar Sectia Psihiatrie Clinica
city: Cuza Voda st, 36, Oradea
country: Romania
facility: Spitalul de Neuropsihiatrie Oradea
city: Gh. Marinescu st.38 ,Targu-Mures
country: Romania
facility: Clinica de Psihiatrie nr.1
city: Octavian Goga st, 17, Arad
country: Romania
facility: Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
city: Sos Bucium, 36, Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie "Socola"
city: Sos. Stefan Cel Mare Nr. 19-21, sect. 2
country: Romania
facility: Spitalul Clinic Colentina Cabinet Psihiatrie Ambulatoriu
city: Str. Bagdazar 12, Sibiu
country: Romania
facility: Spitalul Clinic de Psihiatrie "Ghe. Preda"
city: Str. Clinicilor nr. 3-5, 3400
country: Romania
facility: Spitalul Clinic Judetean de Urgenta -Cluj
city: Str. I.C.Bratianu Nr. 116, Botosani
country: Romania
facility: Spitalul de Psihiatrie Botosani
city: Str. Prundului 7 - 9, Brasov
country: Romania
facility: Spitalul Clinic de Psihiatrie si Neurologie
city: Str. Victor Babes, nr. 43, Cluj Napoca
country: Romania
facility: Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
city: Str.Mihai Eminescu, Nr.18, Brasov
country: Romania
facility: Spitalul de Psihiatrie si Neurologie
Study officials:
affiliation: Sheba Medical Center
name: Mark Weiser, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weiser M, Gershon AA, Rubinstein K, Petcu C, Ladea M, Sima D, Podea D, Keefe RS, Davis JM. A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder. Schizophr Res. 2012 Jun;138(1):35-8. doi: 10.1016/j.schres.2012.02.014. Epub 2012 Apr 4.