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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01092221
First received: March 17, 2010
Last updated: May 6, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Mania
Drug: Allopurinol
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • 1) Change from baseline to day 42 in the YMRS [ Time Frame: from baseline to day 42 ] [ Designated as safety issue: No ]
  • 2) Change from baseline to day 42 in the CGI-BP scale. [ Time Frame: from baseline to day 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1) Change from baseline to day 14 in the YMRS [ Time Frame: from baseline to day 14 ] [ Designated as safety issue: No ]
  • 2) Change from baseline to day 14 in the CGI-BP scale. [ Time Frame: from baseline to day 14 ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: from baseline to day 42 ] [ Designated as safety issue: No ]
  • 4) Rates of discontinuation in the allopurinol group compared to the placebo group [ Time Frame: during the study period (42 days) ] [ Designated as safety issue: No ]

Enrollment: 180
Study Start Date: May 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allopurinol Drug: Allopurinol
Allopurinol 1 capsule 300 mg, BID
Other Name: Alloril, Zylol, Zyloric
Placebo Comparator: Placebo Drug: Placebo
Placebo 1 capsule, 300 mg, BID
Other Name: placebo

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092221

Locations
Israel
Beer-Yaakov Mental Health Center
Beer-Yaakov, Israel, 70350
Sheba Medical Center
Ramat-Gan, Israel, 52621
Lev Hasharon Mental Health Center
Zur-Moshe, Israel
Romania
Spitalul Clinic Judetean, de Urgenta,
Cluj-Napoca,, Cluj-Napoca, Romania, 400012
Jebel
Timis, Jebel Timis, Romania
Spitalul Clinic de Psihiatrie, sectia 14
Berceni st., 10-12, Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie, sectia 10
Berceni st., 10-12, sector 4, Bucharest, Romania, 041902
Spitalul Clinic, sectia 8
Berceni st., sector 4 Bucharest, Romania, 041902
Spitalul de Psihiatrie, Titan
Bld Nicolae Grigorescu, no. 41, Sector 3,, Romania
Spitalul de Psihiatrie, si Neurologie, Brasov
Brasov, Romania, 500123
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3
Bucharest, Romania
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11
Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12
Bucharest, Romania, 041902
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1
Bucharest, Romania, 041902
Sp. Judetean
Focsani, Romania
Sp de Psihiatrie Galati
Galati, Romania
Spitalul Clinic de Psihiatrie, "Socola",
Iasi, Romania, 700282
Spitalul Clinic de Psihiatrie, Socola
Iasi, Romania, 700282
Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
Octavian Goga st, 17, Arad, Romania, 310022
Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu
Sibiu, Romania, 550245
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, 400012
Spitalul de Psihiatrie si Neurologie
Str.Mihai Eminescu, Nr.18, Brasov, Romania, 500079
Spitalul Clinic de Urgenta Clinica "E. Pamfil"
Timisoara, Romania, 300182
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Mark Weiser Sheba Medical Center
  More Information

No publications provided

Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01092221     History of Changes
Other Study ID Numbers: SHEBA-10-7724-MW-CTIL
Study First Received: March 17, 2010
Last Updated: May 6, 2012
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
mania, allopurinol, add-on treatment

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Allopurinol
Antipsychotic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Antimetabolites
Protective Agents
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 26, 2014