Clinical trial NCT00657163: Fluoxetine on Motor Rehabilitation After Ischemic Stroke
Official title: Effects of 3 Months Daily Treatment With Selective Serotonin Reuptake Inhibitor (SSRI, Fluoxetine) on Motor Rehabilitation After Ischemic Stroke. FLAME Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke
Motor Impairment
Keywords: Stroke recovery
Pharmacological modulation
Selective Serotonin Reuptake Inhibitor (SSRI)
Fluoxetine
Brain plasticity
Ischemic Stroke and Motor impairment
Modulation of recovery and cerebral plasticity by Fluoxetine
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2008-04-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression in the Fugl-Meyer Motor Scale
timeFrame: M3 (3 months)
Secondary outcomes:
measure: Fugl-Meyer Stroke Scale
timeFrame: M12 (12 months)
measure: NIH stroke scale
timeFrame: M3 and M12
measure: MADRS depression scale
timeFrame: M3 and M12
measure: Modified Rankin scale
timeFrame: M3 and M12
measure: Mortality
timeFrame: M3 and M12
Other outcomes:
Locations:
city: Besançon
country: France
facility: University Hospital
city: Cergy-Pontoise
country: France
facility: University Hospital René Dubos
city: Dijon
country: France
facility: University Hospital
city: Grenoble
country: France
facility: University Hospital
city: Nantes
country: France
facility: University Hospital
city: Paris
country: France
facility: University Hospital Pitié Salpétrière
city: Paris
country: France
facility: University Hospital Sainte Anne
city: Toulouse
country: France
facility: University Hospital Rangueil
city: Toulouse
country: France
facility: University Hospital Purpan
Study officials:
affiliation: University Hospital, Toulouse
name: François Chollet, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pariente J, Loubinoux I, Carel C, Albucher JF, Leger A, Manelfe C, Rascol O, Chollet F. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol. 2001 Dec;50(6):718-29. doi: 10.1002/ana.1257.
citation: Dam M, Tonin P, De Boni A, Pizzolato G, Casson S, Ermani M, Freo U, Piron L, Battistin L. Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Stroke. 1996 Jul;27(7):1211-4. doi: 10.1161/01.str.27.7.1211.
citation: Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.