Allopurinol Add-on Treatment for Refractory Mania

NCT00643123 | Completed Phase 4 Results

• 1 other identifier: IRB8981
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for treatment resistant mania and mixed mania.

Conditions

Bipolar Disorder; Mixed Mania; Treatment-Resistant Mania

Keywords

Bipolar Disorder; Mania; Mixed mania; Allopurinol; Treatment-Resistant mania

Outcome Measures

Primary Outcomes (1)

• 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

  7 weeks (Baseline and 6 weeks (or last visit date) after baseline

Secondary Outcomes (1)

• Hamilton Depression Scale (HAM-D)

  7 weeks

Study Arms (2)

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.

Drug: Allopurinol

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to placebo and will follow the same protocol as the allopurinol group.

Other: Placebo

Interventions

Allopurinol DRUG

300-600 mg/day over a 6 week period

Also known as: Zyloprim

Allopurinol

Placebo OTHER

Inactive substance

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• 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.

  PMID: 22420596 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Mania

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Felicia Mayes
• Organization: Cedars Sinai Medical Center

mayesf@cshs.org

310-423-0825

Study Officials

• Itai Danovitch, M.D.

  Cedars-Sinai Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman, Department of Psychiatry

Study Record Dates

• First Submitted: March 20, 2008
• First Posted: March 26, 2008
• Study Start: September 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: May 8, 2019
• Results First Posted: April 13, 2018

Record last verified: 2019-05

Locations

US (1)