Official Title: “A Double-Blind, Randomized, Placebo-Controlled 4-Week Study on the Efficacy and Safety of the Purinergic Agents Allopurinol and Dipyridamole in Acute Bipolar Mania.”

This study aims to evaluate the potential antimanic efficacy, safety and tolorability of the purinergic agents allopurinol and dipyridamole as an add-on treatment to lithium in a sample of 180 drug-free manic patients enrolled in a double-blind, placebo-controlled design.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Men and women ages 18 to 65 years, who were inpatients with a diagnosis of manic episode were recruited at the emergency room of Espirita Hospital of Porto Alegre (HEPA), Brazil (n=180) between September 2004 and 2006. The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score>22 on the YMRS at screening to be included. Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram. Patients were randomly assigned to allopurinol 600 mg/day, dipyridamole 200mg or placebo as add-on medication lithium treatment for a 4-week, double-blind trial. The use of adjunctive antipsychotic agents (typical or second-generation drugs) was not allowed during the double-blind period. Adjunctive diazepam was used when necessary (maximum dose=20mg/day). Raters (psychiatrists) were trained together to establish reliability (YMRS =0.90). This study was approved by the Espirita Hospital Ethics Committee-IRB. Written informed consent was obtained from all patients and/or family member.

Possible adverse events were monitored weekly during the follow-up period. Regarding primary outcome measures, we compared the percentage of responders according YMRS score decrease of at least 50% among allopurinol, dipyridamole and placebo groups, using fisher exact test.

Also, the percentage of improvement from baseline to endpoint was obtained and compared among groups using analysis of variances (one-way ANOVA) with Duncan post-hoc test. Remission rates (YMRS scores < 12) were also analyzed. P values < 0.05 were considered statistically significant. Besides completers analysis, intention to treat and LOCF were employed to include data from drop-out patients who were evaluated at visit 3. Possible correlations were measured using Pearson test. Fischer exact test and X2 evaluated response and remission rates. Data are presented as mean ± standard deviation.

Intervention(s) in this Clinical Trial

• Drug: Allopurinol
  • Allopurinol 600mg/day bid for 28 days
• Drug: Dipyridamole
  • Dipyridamole 200mg/day bid for 28 days
• Drug: Placebo
  • Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Lithium 900mg/day plus allopurinol 600mg/day
• Active Comparator: 2
• Placebo Comparator: 3

Primary Measures

• This study aimed to evaluate the potential antimanic efficacy, safety and tolerability
  • Time Frame: 28 days
    

Secondary Measures

• Plasma uric acid levels
  • Time Frame: 28 days
    

Inclusion Criteria:

• The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score>22 on the YMRS at screening to be included.All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram

Exclusion Criteria:

• Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. .

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hospital Espirita de Porto Alegre

Overall Clinical Trial Officials and Contacts

Rodrigo Machado-Vieira, MD, MSc, PhD Principal Investigator Staff Member  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00560079

Study ID Number: 03T-356

ClinicalTrials.gov Identifier: NCT00560079

Health Authority: Brazil: Ministry of Health

IRB (Ethic Committee) homepage: project approval citation- Projeto nº003/03