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

Phase 3

Completed

• Conditions: Mania
• Interventions: Drug: Allopurinol; Drug: Placebo

• Registration Number: NCT01092221
• 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 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.

Study Timeline

• Study First Submitted: 2010-03-17
• Study First Submitted QC: 2010-03-23
• Study First Posted: 2010-03-24
• Study Start: 2010-05
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-06
• Last Update Posted: 2012-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

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.

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. 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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allopurinol	Allopurinol	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
1) Change from baseline to day 42 in the YMRS	from baseline to day 42
2) Change from baseline to day 42 in the CGI-BP scale.	from baseline to day 42

Secondary Outcome Measures

Name	Time	Method
1) Change from baseline to day 14 in the YMRS	from baseline to day 14
2) Change from baseline to day 14 in the CGI-BP scale.	from baseline to day 14
3) Change in the PANSS activation subscale score (total score of 6 PANSS items: Hostility, poor impulse control, excitement, uncooperativeness, poor rapport, and tension) from baseline to final assessment (Day 42).	from baseline to day 42
4) Rates of discontinuation in the allopurinol group compared to the placebo group	during the study period (42 days)

Trial Locations

Locations (24)

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

Sheba Medical Center; 🇮🇱 Ramat-Gan, Israel

Spitalul de Psihiatrie, si Neurologie, Brasov; 🇷🇴 Brasov, Romania

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

Spitalul Clinic Judetean, de Urgenta,; 🇷🇴 Cluj-Napoca,, Cluj-Napoca, Romania

Spitalul Clinic de Psihiatrie, Socola; 🇷🇴 Iasi, Romania

Jebel; 🇷🇴 Timis, Jebel Timis, Romania

Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu; 🇷🇴 Sibiu, Romania

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

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12; 🇷🇴 Bucharest, Romania

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3; 🇷🇴 Bucharest, Romania

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1; 🇷🇴 Bucharest, 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

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

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

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

Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11; 🇷🇴 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

Sp. Judetean; 🇷🇴 Focsani, Romania

Sp de Psihiatrie Galati; 🇷🇴 Galati, Romania

Spitalul Clinic de Urgenta Clinica "E. Pamfil"; 🇷🇴 Timisoara, Romania