Valnoctamide in Mania

• Status: Completed
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Valproic acid is a leading mood stabilizer for the treatment of bipolar disorder. Its well-known teratogenicity limits its use in young women of childbearing age. According to toxicologic studies the teratogenicity of valproate stems from its free carboxylic group. Valnoctamide is an isomer and an analog of valpromide. Unlike valpromide, valnoctamide does not undergo a biotransformation to the corresponding free acid. It is also likely or at least possible that valnoctamide is anti-bipolar. In mice valnoctamide has been shown to be distinctly less teratogenic than valproate. An injection at day 8 of gestation produced only 1% exencephaly (as compared to 0-1% in control mice and 53% in valproate treated mice).

The investigators are performing a double-blind controlled trial of valnoctamide as an anti-bipolar drug. If shown to be anti-bipolar, valnoctamide could be an important valproate substitute for young women with bipolar disorder who are at risk of pregnancy. Patients newly admitted to the Beersheva Mental Health Center may participate if they meet Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV) criteria for mania or schizoaffective disorder, manic type. Patients admitted to the study are treated with risperidone at doses of the physicians' discretion beginning with 2 mg daily on days 1 and 2. Valnoctamide or placebo is begun at doses of 600 mg per day (200 mg three times daily) and increased to 1200 mg (400 mg three times daily) after four days.

Weekly ratings by a psychiatrist blind to the study drug are conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMS), and the Clinical Global Impression (CGI). Weekly blood is drawn for drug levels of valnoctamide to be measured by gas chromatography. Each patient receives valnoctamide or placebo for 5 weeks.

Low teratogenic mood stabilizers are a high priority for current research.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Beersheva Mental Health Center
• Collaborator: Stanley Medical Research Institute

Criteria

Inclusion Criteria:

• Ages 18-60

• Males or females

• DSM-IV criteria for mania or schizoaffective disorder, manic type

• Minimal Young Mania Scale = 20

• Admittance to hospital within previous 72 hours

Exclusion Criteria:

• Any active physical illness

• Pregnancy

• Drug or alcohol abuse

• Suicidal or violent ideation