Official Title: “Effects of 3 Months Daily Treatment With Selective Serotonin Reuptake Inhibitor (SSRI, Fluoxetine) on Motor Rehabilitation After Ischemic Stroke. FLAME Trial”

Recovery from stroke is a major process and, except for acute intravenous thrombolysis, no treatment able to enhance recovery has yet been validated. Some drugs may have a positive effect when combined with physical rehabilitation. Previous studies have shown a potential effect of catecholaminergic drugs on cerebral plasticity of stroke patients. In 2001, our group has demonstrated in a small group of stroke patients (n=8) that a single dose of fluoxetine (Selective Serotonin Reuptake Inhibitor - SSRI) improved motor performance and modulated cerebral plasticity. We conducted a phase IIb prospective, double-blind, randomized, placebo controlled study to assess the effect of a daily treatment with fluoxetin (20 mg) on motor performance in patients with mild to severe motor deficit after ischemic stroke.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2009

We project to include in the study a maximum of 168 patients with a recent (5 to 10 days) ischemic stroke and unilateral motor deficit in order to obtain 100 completed patients. Nine stroke centers in France are involved.

Each patient will receive daily, during three months, 20 mg of fluoxetin or placebo.

Patients will be evaluated at inclusion, day 30, M3 (3 months), M12.

Intervention(s) in this Clinical Trial

• Drug: fluoxetine
  • fluoxetine per os 20 mg daily
• Drug: placebo
  • placebo per os daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • fluoxetine
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Progression in the Fugl-Meyer Motor Scale
  • Time Frame: M3 (3 months)
    Safety Issue?: No

Secondary Measures

• Fugl-Meyer Stroke Scale
  • Time Frame: M12 (12 months)
    Safety Issue?: No
• NIH stroke scale
  • Time Frame: M3 and M12
    Safety Issue?: No
• MADRS depression scale
  • Time Frame: M3 and M12
    Safety Issue?: No
• Modified Rankin scale
  • Time Frame: M3 and M12
    Safety Issue?: No
• Mortality
  • Time Frame: M3 and M12
    Safety Issue?: Yes

Inclusion Criteria:

• Men and women aged from 18 to 85
• No motor relapse from a previous stroke
• Inclusion from day 5 to day 10 after stroke
• Ischemic stroke with unilateral motor deficit
• Motor NIHSS ≥ 5 on the affected side of the body
• NIHSS < 20
• Fugl Meyer Motor Scale <55
• Modified Rankin Scale between 1 and 5
• Informed consent obtained from the subject or a member of his family

Exclusion Criteria:

• Pregnant or breast-feeding woman
• Woman able to procreate without valid contraception
• Subject protected by law
• Concomitant disease with unfavourable prognosis within 1 year
• Drug addiction
• Allergy to fluoxetine
• Hepatic failure (TGO and TGP >2N)
• Permanent Renal failure (Creatinin >180micromol/l)
• Patients treated by tricyclic antidepressant, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor (IMAO), and neuroleptics in the past month
• Depression requiring pharmacological treatment
• Previous stroke with motor relapse
• Fugl Meyer Motor Scale > 55
• Modified Rankin Scale = 0 or 6
• Patients needing carotid surgery within 3 months
• Aphasia preventing correct evaluation of motor and depression scales.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Hospital, Toulouse

Overall Clinical Trial Officials and Contacts

François Chollet, PhD Principal Investigator University Hospital, Toulouse  

Overall Contact: François CHOLLET, PhD  chollet.f@chu-toulouse.fr

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00657163

Study ID Number: 0300501

ClinicalTrials.gov Identifier: NCT00657163

Health Authority: France: Afssaps - French Health Products Safety Agency