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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00864825
• Other study ID #: SHEBA-09-6893-MW-CTIL
• Status: Completed
• Phase: Phase 4
• First received: March 17, 2009
• Last updated: May 6, 2012
• Start date: August 2009
• Est. completion date: January 2010

Study information

• Verified date: May 2012
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• Allopurinol
Allopurinol 1 capsule 300 mg, or placebo, bid (twice a day) for 42 days.

Locations

Country	Name	City	State
Israel	Abrabanel Mental Health Center	Bat Yam
Israel	Beer-Yaakov Mental Health Center	Beer-Yaakov
Israel	Shalvata Mental Health Center	Hod Hasharon
Israel	Jaffa Mental House Center	Jaffa
Israel	Herzog Medical Center, Psychiatry	Jerusalem
Israel	Kfar Shaul Mental Health Center	Jerusalem
Israel	Nes Ziona Mental Health Center	Nes Ziona
Israel	Shaar Menashe Mental Health Center	Shaar Menashe
Israel	Sheba Medical Center, Psychiatry Department	Tel Hashomer, Ramat Gan
Israel	Lev Hasharon Mental Health Center	Zur-Moshe
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	Spitalul Clinic de Psihiatrie, Clinica 9	Berceni st., 10-12, sector 4, Bucharest
Romania	Spitalul Clinic de Psihiatrie, sectia 1	Berceni st., 10-12, sector 4, Bucharest
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 13	Berceni st., 10-12, sector 4, Bucharest
Romania	Spitalul Clinic de Psihiatrie, sectia 3	Berceni st., 10-12, sector 4, Bucharest
Romania	Spitalul Clinic de Psihiatrie, sectia 6	Berceni st., 10-12, sector 4, Bucharest
Romania	Spitalul Clinic, sectia 8	Berceni st., sector 4 Bucharest
Romania	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	Clinica de Psihiatrie nr.1	Gh. Marinescu st.38 ,Targu-Mures
Romania	Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie	Octavian Goga st, 17, Arad
Romania	Spitalul Clinic de Psihiatrie "Socola"	Sos Bucium, 36, Iasi
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 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	Spitalul Clinic Judetean, Sectia Clinica Psihiatrie	Str. Victor Babes, nr. 43, Cluj Napoca
Romania	Spitalul de Psihiatrie si Neurologie	Str.Mihai Eminescu, Nr.18, Brasov

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Countries where clinical trial is conducted

Israel,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PANSS total score.		6 weeks	No
Secondary	PANSS positive, negative and general psychopathology scales, BACS, CGI, Simpson-Angus Scale.		6 weeks	No