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
Information source: Sheba Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mania
Intervention: Allopurinol (Drug); Placebo (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Sheba Medical Center Official(s) and/or principal investigator(s): Mark Weiser, Principal Investigator, Affiliation: Sheba Medical Center
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: 1) Change from baseline to day 42 in the YMRS2) Change from baseline to day 42 in the CGI-BP scale.
Secondary outcome: 1) Change from baseline to day 14 in the YMRS2) Change from baseline to day 14 in the CGI-BP scale. 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). 4) Rates of discontinuation in the allopurinol group compared to the placebo group
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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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.
Locations and Contacts
Beer-Yaakov Mental Health Center, Beer-Yaakov 70350, Israel
Sheba Medical Center, Ramat-Gan 52621, Israel
Lev Hasharon Mental Health Center, Zur-Moshe, Israel
Spitalul Clinic de Psihiatrie, sectia 14, Berceni st., 10-12, Bucharest 041902, Romania
Spitalul Clinic de Psihiatrie, sectia 10, Berceni st., 10-12, sector 4, Bucharest 041902, Romania
Spitalul Clinic, sectia 8, Berceni st., sector 4 Bucharest 041902, Romania
Spitalul de Psihiatrie, Titan, Bld Nicolae Grigorescu, no. 41, Sector 3,, Romania
Spitalul de Psihiatrie, si Neurologie, Brasov, Brasov 500123, Romania
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1, Bucharest 041902, Romania
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11, Bucharest 041902, Romania
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12, Bucharest 041902, Romania
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3, Bucharest, Romania
Sp. Judetean, Focsani, Romania
Sp de Psihiatrie Galati, Galati, Romania
Spitalul Clinic de Psihiatrie, "Socola",, Iasi 700282, Romania
Spitalul Clinic de Psihiatrie, Socola, Iasi 700282, Romania
Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie, Octavian Goga st, 17, Arad 310022, Romania
Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu, Sibiu 550245, 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 400012, Romania
Spitalul de Psihiatrie si Neurologie, Str.Mihai Eminescu, Nr.18, Brasov 500079, Romania
Spitalul Clinic de Urgenta Clinica "E. Pamfil", Timisoara 300182, Romania
Spitalul Clinic Judetean, de Urgenta,, Cluj-Napoca,, Cluj-Napoca 400012, Romania
Jebel, Timis, Jebel Timis, Romania
Additional Information
Starting date: May 2010
Last updated: May 6, 2012
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