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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

Primary Purpose

Mania

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Allopurinol
Placebo
Sponsored by
Sheba Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mania focused on measuring mania, allopurinol, add-on treatment

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beer-Yaakov Mental Health Center
  • Sheba Medical Center
  • Lev Hasharon Mental Health Center
  • Spitalul Clinic Judetean, de Urgenta,
  • Jebel
  • Spitalul Clinic de Psihiatrie, sectia 14
  • Spitalul Clinic de Psihiatrie, sectia 10
  • Spitalul Clinic, sectia 8
  • Spitalul de Psihiatrie, Titan
  • Spitalul de Psihiatrie, si Neurologie, Brasov
  • Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11
  • Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12
  • Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1
  • Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3
  • Sp. Judetean
  • Sp de Psihiatrie Galati
  • Spitalul Clinic de Psihiatrie, "Socola",
  • Spitalul Clinic de Psihiatrie, Socola
  • Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
  • Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu
  • Spitalul de Psihiatrie Botosani
  • Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
  • Spitalul de Psihiatrie si Neurologie
  • Spitalul Clinic de Urgenta Clinica "E. Pamfil"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Allopurinol

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

1) Change from baseline to day 14 in the YMRS
2) 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

Full Information

First Posted
March 17, 2010
Last Updated
May 6, 2012
Sponsor
Sheba Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01092221
Brief 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
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

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sheba Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mania
Keywords
mania, allopurinol, add-on treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allopurinol
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Other Intervention Name(s)
Alloril, Zylol, Zyloric
Intervention Description
Allopurinol 1 capsule 300 mg, BID
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1 capsule, 300 mg, BID
Primary Outcome Measure Information:
Title
1) Change from baseline to day 42 in the YMRS
Time Frame
from baseline to day 42
Title
2) Change from baseline to day 42 in the CGI-BP scale.
Time Frame
from baseline to day 42
Secondary Outcome Measure Information:
Title
1) Change from baseline to day 14 in the YMRS
Time Frame
from baseline to day 14
Title
2) Change from baseline to day 14 in the CGI-BP scale.
Time Frame
from baseline to day 14
Title
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
Title
4) Rates of discontinuation in the allopurinol group compared to the placebo group
Time Frame
during the study period (42 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18-65 years of age, inclusive 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. Willing and able to provide informed consent, after the nature of the study has been fully explained 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. YMRS> 17 Patients receiving one or multiple mood stabilizers, and/or one or more anti-psychotics. Inpatients or outpatients. Exclusion Criteria: Unwilling or unable, in the opinion of the Investigator, to comply with study instructions Pregnant or breast-feeding Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning). Currently taking any of the following medications: warfarin, amoxicilline, ampicilline, theophylline, or mycophenolate mofetil. Likely allergy or sensitivity to Allopurinol At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others. 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. Concurrent delirium, mental retardation, drug-induced psychosis, or history of brain trauma.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Weiser
Organizational Affiliation
Sheba Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beer-Yaakov Mental Health Center
City
Beer-Yaakov
ZIP/Postal Code
70350
Country
Israel
Facility Name
Sheba Medical Center
City
Ramat-Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Lev Hasharon Mental Health Center
City
Zur-Moshe
Country
Israel
Facility Name
Spitalul Clinic Judetean, de Urgenta,
City
Cluj-Napoca,
State/Province
Cluj-Napoca
ZIP/Postal Code
400012
Country
Romania
Facility Name
Jebel
City
Timis
State/Province
Jebel Timis
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie, sectia 14
City
Berceni st., 10-12, Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie, sectia 10
City
Berceni st., 10-12, sector 4, Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul Clinic, sectia 8
City
Berceni st., sector 4 Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul de Psihiatrie, Titan
City
Bld Nicolae Grigorescu, no. 41, Sector 3,
Country
Romania
Facility Name
Spitalul de Psihiatrie, si Neurologie, Brasov
City
Brasov
ZIP/Postal Code
500123
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11
City
Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12
City
Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1
City
Bucharest
ZIP/Postal Code
041902
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3
City
Bucharest
Country
Romania
Facility Name
Sp. Judetean
City
Focsani
Country
Romania
Facility Name
Sp de Psihiatrie Galati
City
Galati
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie, "Socola",
City
Iasi
ZIP/Postal Code
700282
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie, Socola
City
Iasi
ZIP/Postal Code
700282
Country
Romania
Facility Name
Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
City
Octavian Goga st, 17, Arad
ZIP/Postal Code
310022
Country
Romania
Facility Name
Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu
City
Sibiu
ZIP/Postal Code
550245
Country
Romania
Facility Name
Spitalul de Psihiatrie Botosani
City
Str. I.C.Bratianu Nr. 116, Botosani
Country
Romania
Facility Name
Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
City
Str. Victor Babes, nr. 43, Cluj Napoca
ZIP/Postal Code
400012
Country
Romania
Facility Name
Spitalul de Psihiatrie si Neurologie
City
Str.Mihai Eminescu, Nr.18, Brasov
ZIP/Postal Code
500079
Country
Romania
Facility Name
Spitalul Clinic de Urgenta Clinica "E. Pamfil"
City
Timisoara
ZIP/Postal Code
300182
Country
Romania

12. IPD Sharing Statement

Learn more about this trial

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

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