ManiaPhase 3NCT01092221
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
A Phase 3 study testing Allopurinol in people with Mania, run by Sheba Medical Center at 24 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mania
- What is being tested?
- Allopurinol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 24 sitesin 2 countries
- Study dates
- May 2010to Apr 2011
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
Romania21 sites
Spitalul Clinic de Psihiatrie, sectia 14
Berceni St., 10-12, Bucharest, 041902
Spitalul Clinic de Psihiatrie, sectia 10
Berceni St., 10-12, Sector 4, Bucharest, 041902
Spitalul Clinic, sectia 8
Berceni St., Sector 4 Bucharest, 041902
Spitalul de Psihiatrie, Titan
Bld Nicolae Grigorescu, No. 41, Sector 3,
Spitalul de Psihiatrie, si Neurologie, Brasov
Brasov, Brașov County, 500123
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 12
Bucharest, Bucharest, 041902
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 1
Bucharest, Bucharest, 041902
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 3
Bucharest, Bucharest
Spitalul Clinic de Psihiatrie "Prof.Al. Obregia" Sectia 11
Bucharest, 041902
Spitalul Clinic Judetean, de Urgenta,
Cluj-Napoca, Cluj-Napoca, 400012
Sp. Judetean
Focşani, Focsani
Sp de Psihiatrie Galati
Galati, Galați County
Spitalul Clinic de Psihiatrie, "Socola",
Iași, Iaşi, 700282
Spitalul Clinic de Psihiatrie, Socola
Iași, Iaşi, 700282
Spitalul Clinic Judetean De Urgenta, Clinica Psihiatrie
Octavian Goga St, 17, Arad, 310022
Spitalul Clinic de Psihiatrie, "Ghe. Preda" Sibiu
Sibiu, Sibiu County, 550245
Spitalul de Psihiatrie Botosani
Str. I.C.Bratianu Nr. 116, Botosani
Spitalul Clinic Judetean, Sectia Clinica Psihiatrie
Str. Victor Babes, Nr. 43, Cluj Napoca, 400012
Spitalul de Psihiatrie si Neurologie
Str.Mihai Eminescu, Nr.18, Brasov, 500079
Spitalul Clinic de Urgenta Clinica "E. Pamfil"
Timișoara, Timisoara, 300182
Jebel
Timuș, Jebel Timis
Israel3 sites
Beer-Yaakov Mental Health Center
Beer-Yaakov, 70350
Sheba Medical Center
Ramat Gan, 52621
Lev Hasharon Mental Health Center
Tsur Moshe
About this study
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.
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.
Read the 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.
- Conditions
- Mania
- Being tested
- Allopurinol, Placebo
- Keywords
- mania, allopurinol, add-on treatment
- Medical subject headings
- Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Also called Alloril, Zylol, Zyloric
Allopurinol 1 capsule 300 mg, BID
PlaceboDrug
Placebo 1 capsule, 300 mg, BID
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol | Experimental | Not described Receives: Drug: Allopurinol |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
1) Change from baseline to day 42 in the YMRS
Measured: from baseline to day 42
2) Change from baseline to day 42 in the CGI-BP scale.
Measured: from baseline to day 42
Secondary outcomes (4)
1) Change from baseline to day 14 in the YMRS
Measured: from baseline to day 14
2) Change from baseline to day 14 in the CGI-BP scale.
Measured: from baseline to day 14
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).
Measured: from baseline to day 42
4) Rates of discontinuation in the allopurinol group compared to the placebo group
Measured: during the study period (42 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2010 (estimated)
- Study startMay 2010
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ManiaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Mark Weiser, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01092221
- Sponsor's protocol ID
- SHEBA-10-7724-MW-CTIL
- Status last verified
- May 2012
- First submitted
- 17 Mar 2010
- Last updated
- 8 May 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01092221
- Acronym / sponsor ID
- SHEBA-10-7724-MW-CTIL
- Conditions
- Mania
- Keywords
- mania, allopurinol, add-on treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- May 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 24 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allopurinol | Experimental | Drug: Allopurinol |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopurinolAlso: Alloril, Zylol, ZyloricAllopurinol 1 capsule 300 mg, BID | Drug | Allopurinol |
| PlaceboPlacebo 1 capsule, 300 mg, BID | Drug | Placebo |
Primary outcome
1) Change from baseline to day 42 in the YMRS
Time frame: from baseline to day 42
2) Change from baseline to day 42 in the CGI-BP scale.
Time frame: from baseline to day 42
4 secondary outcomes
1) Change from baseline to day 14 in the YMRS
Time frame: from baseline to day 14
2) Change from baseline to day 14 in the CGI-BP scale.
Time frame: from baseline to day 14
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
4) Rates of discontinuation in the allopurinol group compared to the placebo group
Time frame: during the study period (42 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Weiser principal investigator
Sheba Medical Center
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Allopurinol in people with Mania, run by Sheba Medical Center at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Romania, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1) Change from baseline to day 42 in the YMRS (time frame: from baseline to day 42). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2012.