VALID : VAlproate Versus LIthium in Bipolar Disorders

NCT ID: NCT00264173

Last Updated: 2007-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2006-09-30

Brief Summary

Primary Objective :

• To compare the efficacy of valproate to lithium in Bipolar I patients suffering from a manic or a mixed episode according to DSM IV TR (APA 2000) [Diagnostic and Statistical Manual of Mental Disorders (DSM) fourth edition (IV)Text Revision (TR)] and over a periode of 3 weeks and 12 weeks of treatment

Secondary Objective :

• To evaluate the clinical and biological safety of valproate compared to lithium.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Valproate sodium

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with a history of at least one manic episode in the previous three years or before the age of 60 for patients older than 60 at screening, as documented by medical records, or by a relative's report of information corroborating evidence of manic symptomatology for patients already known as bipolar patients. Newly diagnosed patients for bipolar disorder are allowed provided that the diagnosis is based on DSM IV TR[Diagnostic and Statistical Manual of Mental Disorders (DSM) fourth edition (IV)Text Revision (TR)]and that the patient is less than 30 years old.
• Patients with a current diagnosis of Bipolar I Disorder according to DSM IV TR
• Patients suffering from a current manic episode or a mixed episode according to DSM IV TR
• Patients with a minimum total score on the Young Mania Rating Scale (YMRS)of 18 at Screening

• Patients having completed the wash-out period of at least 1 day duration (except for patients receiving no psychiatric treatment or a benzodiazepine at a dose lower than the equivalence of 8 mg of lorazepam and except for patients who only received injectable long-acting neuroleptics at least 7 days prior to Screening)
• Patients with a minimum total score on the Young Mania Rating Scale (YMRS) of 18 at D0

Exclusion Criteria

• Participation in a clinical trial within the three previous months
• Patients with a history of valproate intolerance defined as valproate discontinuation due to medically significant adverse effects
• Patients with a history of lithium intolerance defined as lithium discontinuation due to medically significant adverse effects
• Patients with a Central Nervous System (CNS) neoplasm, demyelinating disease, degenerative neurological disorder, active CNS infection or any progressive disorder that may blur interpretation of the study results
• Patients with a history of seizure disorder, cerebrovascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, known EEG (Electroencephalography) with frank paroxysmal activity or a known CT scan of the brain demonstrating gross structural abnormalities
• Patients with uncontrolled gastro-intestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease
• Patients with renal insufficiency, cardiac insufficiency and Addison's disease
• Patients with past or current pancreatitis
• Patients with acute hepatitis, chronic hepatitis, or family history of severe hepatitis especially drug related, hepatic porphyry
• Patients with a current DSM IV diagnosis of alcohol or substance dependence (with the exception of nicotine or caffeine dependence) or substance abuse with stimulants including but not limited to cocaine, heroin, crack, amphetamines, pseudo-ephedrine, cold medications with phenylephrine or other stimulants. Alcohol or marijuana abuse prior to study entry will be accepted if related to the current manic episode, based on the investigator's judgment
• Pregnancy or lactation. Women of child bearing age should therefore be using a reliable contraceptive method
• Patients that require more than 300 mg of aspirin per day
• Patients with a medical condition which requires the continuous use of a treatment which could interfere with the safety or efficacy evaluation of valproate (anticonvulsant or anticoagulant therapy, zidovudine) or lithium (angiotensin converting enzyme inhibitors, tetracycline, reserpine, calcium channel blockers, triptans)
• Patients who received injectable long-acting neuroleptics less than 7 days prior to Screening
• Patients necessitating an Electro Convulsive Therapy
• Congenital prolongation of the QT interval

• Patients treated with an antidepressant within 5 days prior to randomization (D0)or with fluoxetine within 20 days preceding D0
• Patients with alterations of laboratory tests of potential significance:

• ASAT or ALAT > 3 ULN (Upper Limit of Normal)
• Alkaline phosphatase level > 1.5 ULN
• Serum creatinine > or = to 150 µmol/l
• Hemoglobin < 12 g/dl (men) and <11 g/dl (women)
• Platelets < 150 000 /mm3
• Neutrophils < 1 500 /mm3
• Prothrombin time < 75 %
• TSH (Thyroid-Stimulating Hormone)out of normal ranges
• QTc Bazett > 450 ms for male and > 470 ms for female on ECG (Electrocardiogram).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Principal Investigators

Robert MANFREDI, MD

Role: STUDY_DIRECTOR

Sanofi

Other Identifiers

R_8740

Identifier Type: -

Identifier Source: org_study_id