Allopurinol for Mania: A Randomized Trial Administering Allopurinol vs. Placebo as add-on to Mood Stabilizers and/or Antipsychotics in Patients in a Bipolar Manic Episode

NCT ID: NCT01092221

Last Updated: 2012-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-04-30

Brief Summary

The objective of the study is to evaluate the efficacy of allopurinol, compared to placebo, as add-on to mood stabilizers and/or antipsychotic in the treatment of patients with bipolar disorder, in a manic episode.

Detailed Description

An emerging body of evidence supports a role for dysfunctional purinergic related neurotransmission in mood disorders [1, 2]. 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 striatum. Increased adenosynergic 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.

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

Conditions

Mania

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, BID

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo 1 capsule, 300 mg, BID

Interventions

Allopurinol

Allopurinol 1 capsule 300 mg, BID

Intervention Type: DRUG

Placebo

Placebo 1 capsule, 300 mg, BID

Intervention Type: DRUG

Other Intervention Names

Alloril, Zylol, Zyloric

Eligibility Criteria

Inclusion Criteria

1. Male or female, 18-65 years of age, inclusive

2. 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 bipolar I disorder with the current episode manic (296.4x) or mixed (296.6x), as confirmed by the Modified Structured Clinical Interview for DSM-IV (SCID). In order to ensure that this is an acute manic episode, we will verify that the current manic episode was preceded by a period of euthymia or depression. If inpatients, subjects will be included only up to 14 days after admission. Subjects with psychotic features will be included in the study.

5. YMRS> 17

6. Patients receiving one or multiple mood stabilizers, and/or one or more anti-psychotics.

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. Currently taking any of the following medications: warfarin, amoxicilline, ampicilline, theophylline, or mycophenolate mofetil.

5. Likely allergy or sensitivity to Allopurinol

6. At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.

7. 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.

8. 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

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

Beer-Yaakov Mental Health Center

Beer-Yaakov, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Lev Hasharon Mental Health Center

Tsur Moshe, , Israel

Spitalul de Psihiatrie, si Neurologie, Brasov

Brasov, Brașov County, Romania

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12

Bucharest, Bucharest, Romania

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1

Bucharest, Bucharest, Romania

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3

Bucharest, Bucharest, Romania

Spitalul Clinic Judetean, de Urgenta,

Cluj-Napoca, Cluj-Napoca, Romania

Sp. Judetean

Focşani, Focsani, Romania

Sp de Psihiatrie Galati

Galati, Galați County, Romania

Spitalul Clinic de Psihiatrie, "Socola",

Iași, Iaşi, Romania

Spitalul Clinic de Psihiatrie, Socola

Iași, Iaşi, Romania

Jebel

Timuș, Jebel Timis, Romania

Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu

Sibiu, Sibiu County, Romania

Spitalul Clinic de Urgenta Clinica "E. Pamfil"

Timișoara, Timisoara, Romania

Spitalul Clinic de Psihiatrie, sectia 14

Berceni St., 10-12, Bucharest, , Romania

Spitalul Clinic de Psihiatrie, sectia 10

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 Psihiatrie "Prof.Al. Obregia" Sectia 11

Bucharest, , Romania

Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie

Octavian Goga St, 17, Arad, , Romania

Spitalul de Psihiatrie Botosani

Str. I.C.Bratianu Nr. 116, Botosani, , 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

Other Identifiers

SHEBA-10-7724-MW-CTIL

Identifier Type: -

Identifier Source: org_study_id