Fluoxetine Opens Window to Improve Motor Recovery After Stroke
- Conditions
- Brain IschemiaCerebrovascular DisordersCentral Nervous System DiseasesNervous System DiseasesBrain InfarctionStrokeCerebral InfarctionBrain DiseasesVascular DiseasesCerebrovascular Accident
- Interventions
- Registration Number
- NCT03448159
- Lead Sponsor
- University Health Network, Toronto
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- 25 years of age or older
- Days post stroke must be between 2 to 12 months when enrolled (i.e. day of consent)
- Patient-reported hemiparesis of the lower extremity
- Patients with subarachnoid hemorrhage
- Pre-morbid modified Rankin score > 2
- Substantial premorbid disability or pre-existing deficit or language comprehension deficit that could interfere with assessments
- Diagnosis of major depressive disorder/anxiety disorder requiring antidepressant use within 6 weeks of enrolment
- Taking neuroleptic drugs, benzodiazepines, monoamine oxidase inhibitors within 30 days of enrolment
- Unstable serious medical condition (e.g., terminal cancer, renal or liver failure, congestive heart failure)
- Resting blood pressure exceeding 180/100mmHg
- Requires more than a one person assist for transfer
- Planned surgery that would affect participation in the trial
- Participating in another formal lower limbs exercise program more than one day per week
- 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)
- History of glaucoma
- Patients with a history of thrombocytopenia or clinically significant bleeding disorder or use of NSAID, ASA or other anticoagulants, at the investigators' discretion
- History of convulsive disorders
- Potential pregnancy (per screening algorithm)
- Patients with an ongoing history of illicit drug use and/or alcohol abuse
- Patient unwilling or unable to comply with trial requirements
- Patient unable to understand English or communicate with the study team with staff support or translation services
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Exercise Program An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. During the 3-5 week ramp up period for the experimental group, these participants will take a placebo identical to the 10mg Prozac capsule. After that, the participant will take a placebo identical to the 20mg Prozac capsule for the duration of the exercise intervention (12 weeks). Fluoxetine Hydrochloride Fluoxetine Hydrochloride Fluoxetine (Prozac) will be administered to this group. A ramp up period of 3-5 weeks will take place where the patient takes 10mg of Prozac per day. After that, the participant will take the regular dose of 20mg for the duration of the exercise intervention (12 weeks). Fluoxetine Hydrochloride Exercise Program Fluoxetine (Prozac) will be administered to this group. A ramp up period of 3-5 weeks will take place where the patient takes 10mg of Prozac per day. After that, the participant will take the regular dose of 20mg for the duration of the exercise intervention (12 weeks). Placebo Placebo An over-encapsulated placebo, or "sugar pill" (so it appears identical to the trial drug) will be administered to this group. During the 3-5 week ramp up period for the experimental group, these participants will take a placebo identical to the 10mg Prozac capsule. After that, the participant will take a placebo identical to the 20mg Prozac capsule for the duration of the exercise intervention (12 weeks).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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.
Simple and Choice Reaction Time Test Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Cognitive Measurement
Berg Balance Assessment Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Physical Measurement - Balance Function
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.
Patient Health Questionnaire (PHQ)-9 Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Depression Measurement
Trail Making Test - A & B Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Cognitive Measurement
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
Knee Strength Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Physical Measurement- Lower Limb Strength
Body Mass Index Following completion of the 12-week exercise intervention and 6-months post-exercise intervention Physical Measurement - Health Measurement
Fugl-Meyer Lower Extremity Score 6-months post-exercise intervention Impairment Measurement (see description above)
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
Trial Locations
- Locations (8)
University of Calgary
🇨🇦Calgary, Alberta, Canada
University of British Columbia & GF Strong Centre
🇨🇦Vancouver, British Columbia, Canada
Riverview Health Centre
🇨🇦Winnipeg, Manitoba, Canada
Parkwood Institute
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Toronto Rehabilitation Institute - University Health Network
🇨🇦Toronto, Ontario, Canada
Dalhousie University
🇨🇦Halifax, Nova Scotia, Canada
Memorial University of Newfoundland
🇨🇦St. John's, Newfoundland and Labrador, Canada