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

Mania Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01092221
• Other study ID #: SHEBA-10-7724-MW-CTIL
• Status: Completed
• Phase: Phase 3
• First received: March 17, 2010
• Last updated: May 6, 2012
• Start date: May 2010
• Est. completion date: April 2011

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 mood stabilizers and/or antipsychotic in the treatment of patients with bipolar disorder, in a manic episode.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• 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. 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.

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

• Mania

Intervention

Drug:
• Allopurinol
Allopurinol 1 capsule 300 mg, BID
• Placebo
Placebo 1 capsule, 300 mg, BID

Locations

Country	Name	City	State
Israel	Beer-Yaakov Mental Health Center	Beer-Yaakov
Israel	Sheba Medical Center	Ramat-Gan
Israel	Lev Hasharon Mental Health Center	Zur-Moshe
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 de Psihiatrie, si Neurologie, Brasov	Brasov
Romania	Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1	Bucharest
Romania	Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11	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 Judetean, de Urgenta,	Cluj-Napoca,	Cluj-Napoca
Romania	Sp. Judetean	Focsani
Romania	Sp de Psihiatrie Galati	Galati
Romania	Spitalul Clinic de Psihiatrie, "Socola",	Iasi
Romania	Spitalul Clinic de Psihiatrie, Socola	Iasi
Romania	Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie	Octavian Goga st, 17, Arad
Romania	Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu	Sibiu
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	Jebel	Timis	Jebel Timis
Romania	Spitalul Clinic de Urgenta Clinica "E. Pamfil"	Timisoara

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	1) Change from baseline to day 42 in the YMRS		from baseline to day 42	No
Primary	2) Change from baseline to day 42 in the CGI-BP scale.		from baseline to day 42	No
Secondary	1) Change from baseline to day 14 in the YMRS		from baseline to day 14	No
Secondary	2) Change from baseline to day 14 in the CGI-BP scale.		from baseline to day 14	No
Secondary	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	No
Secondary	4) Rates of discontinuation in the allopurinol group compared to the placebo group		during the study period (42 days)	No