Clinical trial NCT03448159: Fluoxetine Opens Window to Improve Motor Recovery After Stroke
Official title: FLOW Trial: Fluoxetine to Open the Critical Period Time Window to Improve Motor Recovery After Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Cerebrovascular Accident
Cerebral Infarction
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Keywords: Stroke
Exercise
Fluoxetine
Randomized Control Trial
Rehabilitation
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: University of British Columbia
name: Sunnybrook Health Sciences Centre
name: University of Calgary
name: Dalhousie University
name: Parkwood Hospital, London, Ontario
name: Riverview Health Centre Foundation
name: Memorial University of Newfoundland
name: Applied Health Research Centre
name: Brain Canada
name: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery
First posted: 2018-02-27
Enrollment: 52
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: Intervention group (will receive the trial drug, fluoxetine, as well as an exercise intervention) Arm 2: Placebo group (will receive a placebo as well as an exercise intervention
Primary purpose: TREATMENT

Brief summary: The FLOW trial is a randomized placebo-controlled trial analyzing the effect of coupling an anti-depressant, fluoxetine (Prozac), and exercise to improve motor recovery following a stroke.

Detailed description: FLOW Trial is a randomized, placebo-controlled, blinded phase II trial evaluating the efficacy of coupling antidepressant therapy (e.g., selective serotonin reuptake inhibitor - fluoxetine) with exercise rehabilitation across multiple Canadian sites in 176 stroke patients. 88 patients will be enrolled in each arm of the study. Both groups will receive an exercise program in addition to standard of care rehabilitation, but only one group (the intervention group) will receive the active drug fluoxetine.

Study participants will be evaluated at baseline, post-exercise program and 6-months post-exercise program. While enrolled in the study, participants will be required to take part in a 12 week, 3 times per week exercise program. Evaluators and patients will be blind to the treatment administered. The trial is constructed with randomization to remove selection and allocation biases and to ensure greater validity in observed differences in the outcome measures. The Applied Health Research Centre (AHRC) in Toronto will act as the coordinating and analysis center.

Eligibility criteria: Inclusion Criteria:

1. 25 years of age or older
2. Days post stroke must be between 2 to 12 months when enrolled (i.e. day of consent)
3. Patient-reported hemiparesis of the lower extremity

Exclusion Criteria:

1. Patients with subarachnoid hemorrhage
2. Pre-morbid modified Rankin score \> 2
3. Substantial premorbid disability or pre-existing deficit or language comprehension deficit that could interfere with assessments
4. Diagnosis of major depressive disorder/anxiety disorder requiring antidepressant use within 6 weeks of enrolment
5. Taking neuroleptic drugs, benzodiazepines, monoamine oxidase inhibitors within 30 days of enrolment
6. Unstable serious medical condition (e.g., terminal cancer, renal or liver failure, congestive heart failure)
7. Resting blood pressure exceeding 180/100mmHg
8. Requires more than a one person assist for transfer
9. Planned surgery that would affect participation in the trial
10. Participating in another formal lower limbs exercise program more than one day per week
11. History of QT prolongation or concomitant use of clearly identified potential QT prolonging drugs, at the investigators discretion (e.g. amiodarone, bepridil, dysopyramide, dofetilide, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol, phenothiazines, pimozide, ziprasidone, TCAs, halofantrine, cisapride, and probucol)
12. History of glaucoma
13. Patients with a history of thrombocytopenia or clinically significant bleeding disorder or use of NSAID, ASA or other anticoagulants, at the investigators' discretion
14. History of convulsive disorders
15. Potential pregnancy (per screening algorithm)
16. Patients with an ongoing history of illicit drug use and/or alcohol abuse
17. Patient unwilling or unable to comply with trial requirements
18. Patient unable to understand English or communicate with the study team with staff support or translation services

Primary outcomes:
measure: Fugl-Meyer Lower Extremity Score
timeFrame: Following completion of the 12-week exercise intervention
Secondary outcomes:
measure: 6 Minute Walk Test / 10 Meter Walk Test
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Knee Strength
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Berg Balance Assessment
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Grip Strength
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Waist-to-Hip Ratio
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Body Mass Index
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Stroke Impact Scale
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Fugl-Meyer Lower Extremity Score
timeFrame: 6-months post-exercise intervention
measure: Fugl-Meyer Upper Extremity Score
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Patient Health Questionnaire (PHQ)-9
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Simple and Choice Reaction Time Test
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Trail Making Test - A & B
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Montreal Cognitive Assessment (including 5 word recall and clock test)
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
measure: Fasting Blood Draws
timeFrame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia & GF Strong Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Riverview Health Centre
state: Manitoba
city: St. John's
country: Canada
facility: Memorial University of Newfoundland
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Rehabilitation Institute - University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Mark Bayley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia & GF Strong Rehab Centre
name: Courtney Pollock, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Bradley MacIntosh, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Sean Dukelow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Riverview Health Centre
name: Sepideh Pooyania, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial University of Newfoundland
name: Michelle Ploughman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dalhousie University
name: Marilyn Mackay-Lyons, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Parkwood Institute
name: Robert Teasell, MD
role: PRINCIPAL_INVESTIGATOR
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