Clinical trial NCT01092221: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mania
Keywords: mania, allopurinol, add-on treatment
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2010-03-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 1) Change from baseline to day 42 in the YMRS
timeFrame: from baseline to day 42
measure: 2) Change from baseline to day 42 in the CGI-BP scale.
timeFrame: from baseline to day 42
Secondary outcomes:
measure: 1) Change from baseline to day 14 in the YMRS
timeFrame: from baseline to day 14
measure: 2) Change from baseline to day 14 in the CGI-BP scale.
timeFrame: from baseline to day 14
measure: 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).
timeFrame: from baseline to day 42
measure: 4) Rates of discontinuation in the allopurinol group compared to the placebo group
timeFrame: during the study period (42 days)
Other outcomes:
Locations:
city: Beer-Yaakov
country: Israel
facility: Beer-Yaakov Mental Health Center
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
city: Zur-Moshe
country: Israel
facility: Lev Hasharon Mental Health Center
city: Cluj-Napoca,
country: Romania
facility: Spitalul Clinic Judetean, de Urgenta,
state: Cluj-Napoca
city: Timis
country: Romania
facility: Jebel
state: Jebel Timis
city: Berceni st., 10-12, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 14
city: Berceni st., 10-12, sector 4, Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie, sectia 10
city: Berceni st., sector 4 Bucharest
country: Romania
facility: Spitalul Clinic, sectia 8
city: Bld Nicolae Grigorescu, no. 41, Sector 3,
country: Romania
facility: Spitalul de Psihiatrie, Titan
city: Brasov
country: Romania
facility: Spitalul de Psihiatrie, si Neurologie, Brasov
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1
city: Bucharest
country: Romania
facility: Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3
city: Focsani
country: Romania
facility: Sp. Judetean
city: Galati
country: Romania
facility: Sp de Psihiatrie Galati
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie, "Socola",
city: Iasi
country: Romania
facility: Spitalul Clinic de Psihiatrie, Socola
city: Octavian Goga st, 17, Arad
country: Romania
facility: Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
city: Sibiu
country: Romania
facility: Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu
city: Str. I.C.Bratianu Nr. 116, Botosani
country: Romania
facility: Spitalul de Psihiatrie Botosani
city: Str. Victor Babes, nr. 43, Cluj Napoca
country: Romania
facility: Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
city: Str.Mihai Eminescu, Nr.18, Brasov
country: Romania
facility: Spitalul de Psihiatrie si Neurologie
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta Clinica "E. Pamfil"
Study officials:
affiliation: Sheba Medical Center
name: Mark Weiser
role: PRINCIPAL_INVESTIGATOR
References: