Allopurinol Add-on Treatment for Refractory Mania
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|ClinicalTrials.gov Identifier: NCT00643123|
Recruitment Status : Completed
First Posted : March 26, 2008
Results First Posted : April 13, 2018
Last Update Posted : May 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Bipolar Disorder Mixed Mania Treatment-Resistant Mania||Drug: Allopurinol Other: Placebo||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Double-Blind, Placebo Controlled Augmentation Study With Allopurinol for Treatment Resistant Mania|
|Study Start Date :||September 2007|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||June 2010|
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.
300-600 mg/day over a 6 week period
Other Name: Zyloprim
Placebo Comparator: Placebo
Subjects will be randomized to placebo and will follow the same protocol as the allopurinol group.
- 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
- Hamilton Depression Scale (HAM-D) [ Time Frame: 7 weeks ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00643123
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|Study Chair:||Itai Danovitch, M.D.||Cedars-Sinai Medical Center|