Bipolar DisorderPhase 4NCT00643123
Allopurinol Add-on Treatment for Refractory Mania
A Phase 4 study testing Allopurinol in people with Bipolar Disorder and Mixed Mania, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for treatment resistant mania and mixed mania. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bipolar Disorder, Mixed Mania, Treatment-Resistant Mania
- What is being tested?
- Allopurinol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Jun 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must be between ages 18 and 70.
- Subjects must meet DSM-IV criteria for bipolar disorder, most recent episode manic or mixed, at the time of screening confirmed by the Mini International Neuropsychiatric Interview (MINI).
- Subjects must be taking at least one medication for mania (lithium, valproic acid, carbamazepine) at a therapeutic dose for at least 4 weeks.
- Subjects must have non-response or partial response to medications as evidenced by Young Mania Rating Scale (YMRS) score greater than or equal to 14 at screening and at baseline.
- Female subjects must be either postmenopausal for at least 1 year, surgically sterile, abstinent or practicing an effective method of birth control if sexually active. Female subjects must also have a negative urine pregnancy test at screening, baseline and other time points throughout the study.
- Subjects must be able and willing to comply with self-administration of medication or have consistent help/support available.
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- Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
- Subjects must be able and willing to meet or perform study requirements (e.g. answer self-administered questionnaires).
- Subjects must be willing to allow study staff to contact subject's regular psychiatrist while the subject is in the study.
Who cannot join
- Subjects who are unable to provide informed consent.
- Subjects with a serious, unstable medical illness (such as cardiovascular, respiratory, neurologic, hematologic, renal, hepatic, endocrine, immunologic, or other systemic illness), a history of cerebrovascular disease, uncontrolled diabetes mellitus or AIDS. Subjects with chronic illness must be stable and otherwise physically healthy on the basis of a physical examination, medical history, electrocardiogram and the results of blood biochemistry, hematology tests and a urinalysis.
- Subjects with a history of substance abuse or dependence (excluding nicotine and caffeine) according to DSM-IV criteria within last 4 weeks.
- Subjects taking azathioprine, mercaptopurine, apalcillin, and/or amoxicillin.
- Subjects taking dopamine agonists and/or anti-psychotics.
- Subjects who have been intoxicated with alcohol or illicit drugs within 3 days prior to baseline.
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- Subjects with a history of severe pre-existing gastrointestinal narrowing or inability to swallow oral study medication whole with the aid of water.
- Female subjects who are pregnant or nursing.
- Subjects who have previously participated in this study.
- Subjects with an anticipated life expectancy of 6 months or less.
- Subjects who have received an experimental drug or used an experimental medical device within 1 month of screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: A Double-Blind, Placebo Controlled Augmentation Study With Allopurinol for Treatment Resistant Mania
The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for treatment resistant mania and mixed mania.
Read the detailed description
Bipolar disorder is a severe mental disorder with episodes of mania and depression. Current medications for mania can have significant side effects, high costs and the need for blood monitoring. The purpose of this research study is to study the effectiveness of allopurinol, in combination with lithium or valproic acid or carbamazepine, for treatment-resistant bipolar mania and mixed mania. This research study is designed to test the safety and/or effectiveness of allopurinol that has been approved by the U.S. Food and Drug Administration (FDA) for recurrent calcium renal calculus, gout, hyperuricemia (cancer and tumor lysis syndrome), but it is not approved for use in treatment-resistant bipolar mania or mixed mania.
Participants in this double-blind study will be randomly assigned to one of two study groups. The first group will receive the study medication of allopurinol while the second group will receive a placebo. These will be taken in conjunction with current medications and doses. The study will last for 7 weeks (an initial screening, a baseline visit and 4 follow-up visits at weeks 1,2,4, and 6). The initial screening visit will be used to determine whether or not the subject is able to participate in the study. The following will be conducted during the screening visit: Review of medical and psychiatric history along with standard psychiatric assessment exams; Physical examination, including review of prior and current medications and adverse drug effects; An electrocardiogram (ECG) - a painless test which is done by attaching straps or pads to your limbs and chest and recording the electrical pattern of your heart, will be done to record your heart rhythm; About 5 tablespoons of blood will be drawn to assess basic laboratory values that show if you are healthy enough to participate in the study; Blood levels of lithium, valproic acid, and/or carbamazepine will be measured; A urine sample will be collected to test for the presence of illegal drugs and for pregnancy test (if you are a female of child-bearing potential); Collection of demographic data (e.g., age, gender, marital status, social and vocational status) and other information including health beliefs, and knowledge of illness. At the baseline visit the participant will be given questionnaires related to mood, quality of life, disability, medications, and side effects. The participant's vitals (temperature, weight, heart rate, and blood pressure) will be measured. The participant will be randomized to treatment (300 mg of allopurinol/day) or placebo. After week one at the Week 1 visit, those that have tolerated the dosage of allopurinol will get an increased dosage. The participant will also complete a set of questionnaires. Vitals will be taken. The remaining follow-up visits will be similar to visit one except that there will be no more increases in dosage; Week 2 will include a blood draw to measure levels of lithium, valproic acid, and/or carbamazepine in the participant's blood, and the final visit at Week 6 will in addition include a blood draw, and exit physical exam, and a urine sample will be collected.
- Conditions
- Bipolar Disorder, Mixed Mania, Treatment-Resistant Mania
- Being tested
- Allopurinol, Placebo
- Keywords
- Bipolar Disorder, Mania, Mixed mania, Allopurinol, Treatment-Resistant mania
- Medical subject headings
- Bipolar Disorder, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Also called Zyloprim
300-600 mg/day over a 6 week period
PlaceboOther
Inactive substance
| Study group | Role | What they receive |
|---|---|---|
| Allopurinol | Experimental | Subjects will be randomized to allopurinol at a fixed dose of 300 mg/day for the first week and then 600mg/day while continuing their current medications during the 7-week study. A battery of assessments will be administered at baseline and weeks 1, 2, 4, 6 after baseline. At each assessment, subjects will also be asked about side effects including potential side effects of allopurinol. Side effects will be assessed by the Treatment Emergent Side Effects Scale. Serum levels of lithium, valproic acid, carbamazepine, atypical antipsychotics or atypical antipsychotic metabolite, uric acid blood levels will be drawn at screen and at week 6 after baseline. Subjects taking only lithium, valproic acid, and/or carbamazepine will also have their serum levels drawn at week 2. Receives: Drug: Allopurinol |
| Placebo | Placebo comparator | Subjects will be randomized to placebo and will follow the same protocol as the allopurinol group. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Young Mania Rating Scale (YMRS)
The YMRS is an 11-item, clinician-administered rating scale to assess the severity of manic symptoms before, during and after treatment. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. A score of 0 indicates the behavior is absent, whereas a score of 4 or 8 indicates the behavior is present and severe.
The change in score between Baseline and the Completion Visit will be reported. Ideally, the two time points will be Baseline and 6 Weeks after Baseline, but, if a subject terminates early, his/her last YMRS score will be carried forward to the final visit.
The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms. A score of 0-12 indicates the absence of mania or a very mild manic state, a score of 13-20 or higher indicates a mild man
Measured: 7 weeks (Baseline and 6 weeks (or last visit date) after baseline
Secondary outcomes (1)
Hamilton Depression Scale (HAM-D)
The Hamilton Depression Rating Scale (HAM-D) is a clinician-administered tool used to determine a patient's level of depression before, during, and after treatment. A 28-item HAM-D form was used but only the first 17 questions are used in the assessment for depression. Of the first 17 questions, eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. The sum of the scores from the first 17 questions is: 0-7 = normal, 8-13 = mild depression, 14-18 = moderate depression, 19-22=severe depression and ≥ 23=very severe depression.
Questions 18-28 are scored similarly and assess sleep disorders, paranoid behavior, motor dysfunction, psychosis, and weight gain, etc.
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2008 (estimated)
- Study startSep 2007
- Primary completionJun 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Principal investigator, Itai Danovitch, Cedars-Sinai Medical Center
- Investigators
- Itai Danovitch, M.D., Study chair, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00643123
- Sponsor's protocol ID
- IRB8981
- Status last verified
- May 2019
- First submitted
- 20 Mar 2008
- Last updated
- 8 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Fan A, Berg A, Bresee C, Glassman LH, Rapaport MH. Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study. Bipolar Disord. 2012 Mar;14(2):206-10. doi: 10.1111/j.1399-5618.2012.01001.x.
PubMed 22420596
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo Controlled Augmentation Study With Allopurinol for Treatment Resistant Mania
- ClinicalTrials.gov ID
- NCT00643123
- Acronym / sponsor ID
- IRB8981
- Conditions
- Bipolar Disorder, Mixed Mania, Treatment-Resistant Mania
- Keywords
- Bipolar Disorder, Mania, Mixed mania, Allopurinol, Treatment-Resistant mania
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Sep 2007
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 26 Mar 2008 (estimated)
- Results
- Posted 13 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for treatment resistant mania and mixed mania.
Detailed description
Bipolar disorder is a severe mental disorder with episodes of mania and depression. Current medications for mania can have significant side effects, high costs and the need for blood monitoring. The purpose of this research study is to study the effectiveness of allopurinol, in combination with lithium or valproic acid or carbamazepine, for treatment-resistant bipolar mania and mixed mania. This research study is designed to test the safety and/or effectiveness of allopurinol that has been approved by the U.S. Food and Drug Administration (FDA) for recurrent calcium renal calculus, gout, hyperuricemia (cancer and tumor lysis syndrome), but it is not approved for use in treatment-resistant bipolar mania or mixed mania.
Participants in this double-blind study will be randomly assigned to one of two study groups. The first group will receive the study medication of allopurinol while the second group will receive a placebo. These will be taken in conjunction with current medications and doses. The study will last for 7 weeks (an initial screening, a baseline visit and 4 follow-up visits at weeks 1,2,4, and 6). The initial screening visit will be used to determine whether or not the subject is able to participate in the study. The following will be conducted during the screening visit: Review of medical and psychiatric history along with standard psychiatric assessment exams; Physical examination, including review of prior and current medications and adverse drug effects; An electrocardiogram (ECG) - a painless test which is done by attaching straps or pads to your limbs and chest and recording the electrical pattern of your heart, will be done to record your heart rhythm; About 5 tablespoons of blood will be drawn to assess basic laboratory values that show if you are healthy enough to participate in the study; Blood levels of lithium, valproic acid, and/or carbamazepine will be measured; A urine sample will be collected to test for the presence of illegal drugs and for pregnancy test (if you are a female of child-bearing potential); Collection of demographic data (e.g., age, gender, marital status, social and vocational status) and other information including health beliefs, and knowledge of illness. At the baseline visit the participant will be given questionnaires related to mood, quality of life, disability, medications, and side effects. The participant's vitals (temperature, weight, heart rate, and blood pressure) will be measured. The participant will be randomized to treatment (300 mg of allopurinol/day) or placebo. After week one at the Week 1 visit, those that have tolerated the dosage of allopurinol will get an increased dosage. The participant will also complete a set of questionnaires. Vitals will be taken. The remaining follow-up visits will be similar to visit one except that there will be no more increases in dosage; Week 2 will include a blood draw to measure levels of lithium, valproic acid, and/or carbamazepine in the participant's blood, and the final visit at Week 6 will in addition include a blood draw, and exit physical exam, and a urine sample will be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Allopurinol | Experimental | Drug: AllopurinolSubjects will be randomized to allopurinol at a fixed dose of 300 mg/day for the first week and then 600mg/day while continuing their current medications during the 7-week study. A battery of assessments will be administered at baseline and weeks 1, 2, 4, 6 after baseline. At each assessment, subjects will also be asked about side effects including potential side effects of allopurinol. Side effects will be assessed by the Treatment Emergent Side Effects Scale. Serum levels of lithium, valproic acid, carbamazepine, atypical antipsychotics or atypical antipsychotic metabolite, uric acid blood levels will be drawn at screen and at week 6 after baseline. Subjects taking only lithium, valproic acid, and/or carbamazepine will also have their serum levels drawn at week 2. |
| Placebo | Placebo comparator | Other: PlaceboSubjects will be randomized to placebo and will follow the same protocol as the allopurinol group. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects must be between ages 18 and 70.
- Subjects must meet DSM-IV criteria for bipolar disorder, most recent episode manic or mixed, at the time of screening confirmed by the Mini International Neuropsychiatric Interview (MINI).
- Subjects must be taking at least one medication for mania (lithium, valproic acid, carbamazepine) at a therapeutic dose for at least 4 weeks.
- Subjects must have non-response or partial response to medications as evidenced by Young Mania Rating Scale (YMRS) score greater than or equal to 14 at screening and at baseline.
- Female subjects must be either postmenopausal for at least 1 year, surgically sterile, abstinent or practicing an effective method of birth control if sexually active. Female subjects must also have a negative urine pregnancy test at screening, baseline and other time points throughout the study.
Key exclusion criteria (11 listed)
- Subjects who are unable to provide informed consent.
- Subjects with a serious, unstable medical illness (such as cardiovascular, respiratory, neurologic, hematologic, renal, hepatic, endocrine, immunologic, or other systemic illness), a history of cerebrovascular disease, uncontrolled diabetes mellitus or AIDS. Subjects with chronic illness must be stable and otherwise physically healthy on the basis of a physical examination, medical history, electrocardiogram and the results of blood biochemistry, hematology tests and a urinalysis.
- Subjects with a history of substance abuse or dependence (excluding nicotine and caffeine) according to DSM-IV criteria within last 4 weeks.
- Subjects taking azathioprine, mercaptopurine, apalcillin, and/or amoxicillin.
- Subjects taking dopamine agonists and/or anti-psychotics.
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: Zyloprim300-600 mg/day over a 6 week period | Drug | Allopurinol |
| PlaceboInactive substance | Other | Placebo |
Primary outcome
Young Mania Rating Scale (YMRS)
Time frame: 7 weeks (Baseline and 6 weeks (or last visit date) after baseline
The YMRS is an 11-item, clinician-administered rating scale to assess the severity of manic symptoms before, during and after treatment. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. A score of 0 indicates the behavior is absent, whereas a score of 4 or 8 indicates the behavior is present and severe. The change in score between Baseline and the Completion Visit will be reported. Ideally, the two time points will be Baseline and 6 Weeks after Baseline, but, if a subject terminates early, his/her last YMRS score will be carried forward to the final visit. The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms. A score of 0-12 indicates the absence of mania or a very mild manic state, a score of 13-20 or higher indicates a mild man
1 secondary outcome
Hamilton Depression Scale (HAM-D)
Time frame: 7 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22420596Fan A, Berg A, Bresee C, Glassman LH, Rapaport MH. Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study. Bipolar Disord. 2012 Mar;14(2):206-10. doi: 10.1111/j.1399-5618.2012.01001.x.
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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.
Itai Danovitch, M.D. study chair
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Allopurinol in people with Bipolar Disorder and Mixed Mania, run by Cedars-Sinai Medical Center at 1 site in United States.
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 9 inclusion and 11 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 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Young Mania Rating Scale (YMRS) (time frame: 7 weeks (Baseline and 6 weeks (or last visit date) after baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00643123, which also lists 1 linked publication.
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 2019.