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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02063425
Recruitment Status : Terminated (Not enough recruitment)
First Posted : February 14, 2014
Last Update Posted : October 20, 2017
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier St Anne

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cerebral Infarction Drug: Fluoxetine Drug: Placebo of fluoxetine Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: "Evaluation by Transcranial Magnetic Stimulation of the Benefit of Fluoxetine on Motor Recovery After Stroke"
Actual Study Start Date : February 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Fluoxetine

Arm Intervention/treatment
Active Comparator: Fluoxetine Drug: Fluoxetine
1 pill of 20mg / day, during 3 months
Other Name: Patients receiving fluoxetine

Placebo Comparator: Placebo Drug: Placebo of fluoxetine
1 pill of 20mg/day, during 3 months
Other Name: Patients receiving placebo




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


  4. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02063425


Locations
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France
Centre Hospitalier Sainte-Anne
Paris, France, 75674
Sponsors and Collaborators
Centre Hospitalier St Anne
Investigators
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Study Director: Jean-Claude BARON, MD Centre Hospitalier Sainte-Anne
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Responsible Party: Centre Hospitalier St Anne
ClinicalTrials.gov Identifier: NCT02063425    
Other Study ID Numbers: D505
2013-001313-32 ( EudraCT Number )
First Posted: February 14, 2014    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2017
Keywords provided by Centre Hospitalier St Anne:
Motor recovery
Fluoxetine
Transcranial magnetic stimulation
stroke
Additional relevant MeSH terms:
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Cerebral Infarction
Infarction
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Brain Infarction
Brain Ischemia
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors