Clinical trial NCT00732251: Allopurinol Maintenance Study for Bipolar Disorder
Official title: An Open Label, Naturalistic Study With Allopurinol Augmentation for Prevention of Mania in Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bipolar Disorder
Mania
Mixed Mania
Keywords: Bipolar Disorder
Stable Bipolar Disorder
Mania
Mixed mania
Allopurinol
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: West Coast College of Biological Psychiatry Inc
First posted: 2008-08-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for the prevention of mania in bipolar disorder patients with currently stable mood.

Detailed description: The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for the prevention of mania in bipolar disorder patients with currently stable mood. Bipolar disorder is a mental disorder with severe mood swings (mania and depression). Despite the development of medications for mania, they may have significant side effects, high costs and the need for serum level monitoring. These factors adversely affect medication compliance in bipolar patients. One recent study indicated the efficacy of allopurinol in the treatment of bipolar mania. Our hypothesis is that the addition of allopurinol to standard medications for bipolar disorder will decrease the recurrences of manic episodes compared to standard medications.

This study will recruit bipolar disorder patients currently mood stable on a therapeutic dose of an anti-manic medication. Stable mood will be defined as a Young Mania Rating Scale score ≤10 and Hamilton Depression Rating Scale ≤10. Subjects must have a diagnosis of bipolar disorder confirmed by the Mini International Neuropsychiatric Interview. Young Mania Rating Scale and Mini International Neuropsychiatric Interview are common research questionnaires used in bipolar disorder studies. Potential subjects will be identified and approached during an outpatient clinical visit by a member of the research team and identified by their treating physicians and referred to the researchers.

This study involves adding allopurinol to subjects' current bipolar medications. This study will be a open label, naturalistic study. The subject will be examined monthly for manic symptoms for 2 years. Semi-structured interviews and study questionnaires will be administered to subjects at each visit. Monthly Follow-up Study Visits (once per month for 2 years - Months 1-5, 7-11, 13-17, 19-23) may be conducted either in-person or over the phone. All of the questionnaires will be administered by a clinician if the visit is completed over the phone. However, the 6-month interval visits (Months 6, 12, 18, and 24) must be done at the research center.

The primary outcome measure will be the number of manic episodes in the 2 year study period. A manic episode will be defined by a Young Mania Rating Scale score ≥20.

Eligibility criteria: Inclusion Criteria:

1. Subjects must be between ages 18 and 70.
2. Subjects must meet diagnostic and statistical manual of mental disorders 4th edition criteria for bipolar disorder confirmed by the Mini International Neuropsychiatric Interview.
3. Subjects must be taking at least one medication for mania at a therapeutic dose for at least 2 weeks.
4. Subjects must have been diagnosed with bipolar disorder, type 1, for at least 2 years prior to baseline.
5. Subjects must have adequate response to medications as evidenced by Young Mania Rating Scale score less than or equal to 10 at screening and at baseline.
6. Subjects must have adequate response to medications as evidenced by Hamilton Depression Rating Scale score less than or equal to 10 at screening and at baseline.
7. Subjects must have had at least 1 manic episode in the 2 year period prior to entering the study.
8. 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. Acceptable methods of birth control during this study are regular use of contraceptive pills, intra-uterine devices, barrier methods or abstinence. Female subjects must also have a negative urine pregnancy test at screening, baseline and other time points throughout the study.
9. Subjects must be able and willing to comply with self-administration of medication or have consistent help/support available.
10. 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.
11. Subjects must be able and willing to meet or perform study requirements (e.g. answer self-administered questionnaires).
12. Subjects must be willing to allow study staff to contact subject's regular psychiatrist while the subject is in the study.

Exclusion Criteria:

1. Subjects who are unable to provide informed consent.
2. 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 acquired immunodeficiency syndrome (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.
3. Subjects who develop a medical condition during participation which can affect mood stability (i.e. seizure disorder, brain tumors, brain trauma, stroke, multiple sclerosis, etc.)
4. Subjects who develop substance abuse or dependence during participation in the study.
5. Subjects taking azathioprine, mercaptopurine, apalcillin, and/or amoxicillin.
6. Subjects who have been intoxicated with alcohol or drugs within the last 72hrs.
7. Subjects with a history of severe pre-existing gastrointestinal narrowing or inability to swallow oral study medication whole with the aid of water.
8. Female subjects who are pregnant or nursing.
9. Subjects who have previously participated in this study.
10. Subjects with an anticipated life expectancy of 6 months or less.
11. Subjects who have received an experimental drug or used an experimental medical device within 1 month of screening.

Primary outcomes:
measure: Number of Manic Episodes According to the Young Mania Rating Scale
timeFrame: 2 Years
Secondary outcomes:
measure: Number of Depressive Episodes Per Patient Visit According to the Hamilton Depression Scale
timeFrame: 2 years
measure: Number of Psychiatric Hospitalizations
timeFrame: 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Itai Danovitch, MD
role: STUDY_CHAIR
References: