Brain Diseases, Brain Infarction, Brain Ischemia, Central Nervous System Diseases, Cerebral Infarction, Cerebrovascular Accident, Cerebrovascular Disorders, Nervous System Diseases, Stroke, Vascular Diseases
Conditions
Keywords
Stroke, Exercise, Fluoxetine, Randomized Control Trial, Rehabilitation
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.
Interventions
Half of the participants will take fluoxetine for a period of 15-17 weeks (depending on ramp-up period).
OTHERPlacebo
Half of the participants will take the a placebo for a period of 15-17 weeks (depending on ramp-up period).
BEHAVIORALExercise Program
All participants will take part in a 12-week exercise program. The program will run 3 times/week, 1 hour/class.
Sponsors
University of British Columbia
Sunnybrook Health Sciences Centre
University of Calgary
Dalhousie University
Parkwood Hospital, London, Ontario
Riverview Health Centre Foundation
Memorial University of Newfoundland
Applied Health Research Centre
Brain Canada
Heart and Stroke Foundation Canadian Partnership for Stroke Recovery
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fugl-Meyer Lower Extremity Score | Following completion of the 12-week exercise intervention | Fugl-Meyer Lower Extremity Assessment assesses motor and sensorimotor impairment in the lower extremities. Total score is between 0 and 34. Sub-scales include: proximal (0-18), knee/ankle (0-10) and coordination/speed (0-6). Higher scores indicate better performance. Sub-scale scores are summed to calculate total score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Knee Strength | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement- Lower Limb Strength |
| Berg Balance Assessment | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement - Balance Function |
| Grip Strength | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement - Grip Strength |
| Waist-to-Hip Ratio | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement - Health Measurement |
| Body Mass Index | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement - Health Measurement |
| Stroke Impact Scale | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Stroke-specific, self-report, health status measure. Assesses multiple domains on a 5-point Likert scale. Domains include: strength (4-20), hand function (5-25), activities of daily living/instrumental activities of daily living (10-50), mobility (9-45), communication (7-35), emotion (9-45), memory and thinking (7-35), and participation (8-40). An extra question asks that the patient rate on a scale from 0 - 100 how much they feel that he/she has recovered from his/her stroke. The 4 physical domains (strength, hand function, mobility and activities of daily living) can be summed together to create a single, physical dimension score (28-140) while all other domains should remain separate. Higher scores indicate better function. |
| 6 Minute Walk Test / 10 Meter Walk Test | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Physical Measurement - Ambulatory Function |
| Fugl-Meyer Upper Extremity Score | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Fugl-Meyer Upper Extremity Assessment assesses motor and sensorimotor impairment in the upper extremities. There is no total score for this measure. Sub-scales include: upper extremity (0-36), wrist (0-10), hand (0-14), coordination/speed (0-6) (which can be combined to form a total motor function score out of 66), and sensation (0-4). Higher scores indicate better performance. |
| Patient Health Questionnaire (PHQ)-9 | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Depression Measurement |
| Simple and Choice Reaction Time Test | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Cognitive Measurement |
| Trail Making Test - A & B | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Cognitive Measurement |
| Montreal Cognitive Assessment (including 5 word recall and clock test) | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Cognitive Measurement |
| Fasting Blood Draws | Following completion of the 12-week exercise intervention and 6-months post-exercise intervention | Biological Biomarker |
| Fugl-Meyer Lower Extremity Score | 6-months post-exercise intervention | Impairment Measurement (see description above) |
Countries
Canada
Outcome results
None listed