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

NCT ID: NCT00864825

Last Updated: 2012-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2010-01-31

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Allopurinol

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Allopurinol

Intervention Type: DRUG

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

Interventions

Allopurinol

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

Intervention Type: DRUG

Other Intervention Names

Alloril, Zylol, Zyloric

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Weiser, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

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

Ness 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

Tsur Moshe, , Israel

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 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 1

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, , Romania

Countries

Israel; Romania

References

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.

Reference Type: DERIVED

PMID: 22483162 (View on PubMed)

Other Identifiers

SHEBA-09-6893-MW-CTIL

Identifier Type: -

Identifier Source: org_study_id