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:
Sheba Medical Center
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
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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:
- 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.
Contacts and Locations
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 May 16, 2013