"Evaluation by Transcranial Magnetic Stimulation of the Benefit of Fluoxetine on Motor Recovery After Stroke" (EFLUSTIM)

October 18, 2017 updated by: Centre Hospitalier St Anne

The objective of this study is to better characterize the mechanisms of action of fluoxetine in motor recovery and more specifically to identify the neurophysiological substrate underlying fluoxetine-induced motor recovery in stroke.

In this study, the investigators propose to use transcranial magnetic stimulation (TMS) to assess the effect of a chronic treatment of fluoxetine on corticospinal excitability and integrity.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Recently, a phase IIb clinical trial (Chollet et al., 2011 - FLAME study) revealed that early administration of standard-dose oral fluoxetine (a selective serotonin re-uptake inhibitor widely used as antidepressant) to patients with subacute ischaemic stroke and moderate to severe motor deficit in the upper extremity enhanced motor recovery after 3 months, as assessed by the Fugl-Meyer motor scale, suggesting that fluoxetine could be a promising drug to promote recovery in stroke patients. However, the mechanisms, and their specificity, by which fluoxetine improves motor function after stroke remain poorly understood.

The overall objective of this proposal is to better characterize the mechanisms of action of fluoxetine in motor recovery and more specifically to identify the neurophysiological substrate underlying fluoxetine-induced motor recovery in stroke.

The corticospinal system plays a key role in voluntary activation of upper limb muscles. Its integrity has been related to spontaneous (but incomplete) recovery after stroke. So far, the effect of fluoxetine on corticospinal excitability and integrity has been poorly explored although this drug appears promising to promote motor recovery.

In this study, the investigators propose to use transcranial magnetic stimulation (TMS) to assess the effect of a chronic treatment of fluoxetine on corticospinal excitability and integrity. The investigators believe that this approach will be suitable to determine the mechanisms of action of this drug on motor recovery after stroke.

The investigators will assess in a double-blind, monocentric (Saint-Anne Hospital Stroke center), randomised, placebo-controlled study, the effect of a chronic treatment of fluoxetine on corticospinal excitability and integrity using TMS in 40 patients suffering from ischaemic stroke with hemiplegia or hemiparesis affecting motor hand functions.

By coupling TMS, visuomotor grip tracking task and several clinical scales, the investigators' results will allow a more system-specific assessment than the Fugl-Meyer motor scale of fluoxetine-induced motor hand recovery in stroke. We believe that this study will support the beneficial effect of fluoxetine to promote motor recovery in stroke and will open new vistas for treatment options using fluoxetine in patients with motor impairments. It is expected that this study will provide preliminary data that will be subsequently used to design new, more focused, clinical trials.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75674
        • Centre Hospitalier Sainte-Anne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Man and women, aged from 18 to 80 years.
  • Social security affiliation
  • Inclusion from day 3 to day 15 after stroke or brain haemorrhage
  • Hemiparesia with upper limb motor deficit (Fugl-Meyer score - hand < or = 10)
  • Informed consent

Exclusion Criteria:

  • Score NIHSS > 20
  • Depression (criteria DSM5-R) with MADRS score > 19
  • History of recurrent bipolar or depressive disorders.
  • History of behavior or suicidal idea
  • Family history of extension of the interval QT or congenital long interval QT
  • History of clinical stroke
  • Aphasia preventing correct evaluation of motor and depression scales.
  • Patients treated by antidepressant drugs, monoamine oxidase inhibitor (IMAO), and neuroleptics in the past month
  • Benzodiazepines within 48 hours preceding inclusion.
  • Intolerance or allergy to fluoxetine (Sandoz® 20 mg pill)
  • Severe swallowing disorders preventing oral administration of the treatment
  • Planned carotid surgery
  • Pregnant or breast-feeding woman
  • Hepatic failure (TGO and TGP >2N); severe renal failure (creatinine >180micromol/l)
  • Concomitant severe disease not allowing follow-up.
  • Participation to another therapeutic study.
  • Contraindication to MRI and TMS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo of fluoxetine
1 pill of 20mg/day, during 3 months
Other Names:
  • Patients receiving placebo
Active Comparator: Fluoxetine
Drug: Fluoxetine
1 pill of 20mg / day, during 3 months
Other Names:
  • Patients receiving fluoxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Slope of the curve of recruitment of the PEMs
Time Frame: M3
Significant difference, between the treated group and the group control, of the slope of the curve of recruitment of the PEMs between the beginning (D0) and the end of the treatment (processing) (M3).
M3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Slope of recruitment of the PEMs
Time Frame: D0, M3, M6
Effect of a first dose of fluoxétine on the slope of recruitment of the PEMs.
D0, M3, M6
Slope of recruitment of the PEMs
Time Frame: D0, M3, M6
Persistence of fluoxétine effect on the slope of recruitment of the PEMs to M6.
D0, M3, M6
Index finger force control in paretic hand under time-course of treatment of Fluoxetine
Time Frame: D0, M3, M6

A visuomotor tracking task is used to measure accuracy of force control (NewtonSecond, Ns) and time taken to release force (release duration, ms). Performance between time-points will be measured (Ns, before-after treatment).

Effects of fluoxetine on force control parameters (e.g., accuracy and release duration) in paretic hand.
D0, M3, M6
in index finger force control in non-paretic hand under time-course of treatment of Fluoxetine
Time Frame: D0, M3, M6
Same visuomotor tracking mesures as above but acquired in non-paretic hand. Effects of fluoxetine on the non-affected hand (error, Ns; release duration, ms).
D0, M3, M6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier St Anne

Investigators

  • Study Director: Jean-Claude BARON, MD, Centre Hospitalier Sainte-Anne

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2014

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

January 6, 2014

First Submitted That Met QC Criteria

February 13, 2014

First Posted (Estimate)

February 14, 2014

Study Record Updates

Last Update Posted (Actual)

October 20, 2017

Last Update Submitted That Met QC Criteria

October 18, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D505
  • 2013-001313-32 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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