Fluoxetine on Motor Rehabilitation After Ischemic Stroke

Condition(s) targeted: Ischemic Stroke; Motor Impairment

Intervention: fluoxetine (Drug); placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University Hospital, Toulouse

Official(s) and/or principal investigator(s):
François Chollet, PhD, Principal Investigator, Affiliation: University Hospital, Toulouse

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

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.

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

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

Primary outcome: Progression in the Fugl-Meyer Motor Scale

Secondary outcome:

Fugl-Meyer Stroke Scale

NIH stroke scale

MADRS depression scale

Modified Rankin scale

Mortality

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.

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Both.

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.

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

University Hospital Purpan, Toulouse 31059, France; Recruiting
François Chollet, MD, Principal Investigator
Jean Tardy, MD, Sub-Investigator
Jean-François Albucher, Sub-Investigator

University Hospital, Besançon 25030, France; Recruiting
Thierry Moulin, Principal Investigator

University Hospital, Dijon 21000, France; Recruiting
Maurice Giroud, Principal Investigator

University Hospital, Grenoble 38048, France; Recruiting
Marc Hommel, Principal Investigator

University Hospital, Nantes 44093, France; Recruiting
Benoit Guillon, Principal Investigator

University Hospital Sainte Anne, Paris 75674, France; Recruiting
Jean-Louis MAS, Principal Investigator

University Hospital Pitié Salpétrière, Paris 75651, France; Recruiting
Yves Samson, Principal Investigator

University Hospital René Dubos, Cergy-Pontoise 95303, France; Recruiting
Jérome Servan, Principal Investigator

University Hospital Rangueil, Toulouse 31052, France; Recruiting
Vincent Larrue, Principal Investigator
Jean Tardy, MD, Sub-Investigator

Related publications:

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.

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.

Starting date: March 2005
Ending date: March 2010
Last updated: April 11, 2008