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Fluoxetine Opens Window to Improve Motor Recovery After Stroke (FLOW)

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ClinicalTrials.gov Identifier: NCT03448159
Recruitment Status : Recruiting
First Posted : February 27, 2018
Last Update Posted : August 20, 2019
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE February 21, 2018
First Posted Date  ICMJE February 27, 2018
Last Update Posted Date August 20, 2019
Actual Study Start Date  ICMJE January 1, 2019
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
Fugl-Meyer Lower Extremity Score [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
Fugl-Meyer Lower Extremity Score [ Time Frame: Following completion of the 12-week exercise intervention ]
Fugl-Meyer Assessment (FMA) scale is an index to assess the sensorimotor impairment in individuals who have had stroke.
Change History Complete list of historical versions of study NCT03448159 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
  • 6 Minute Walk Test / 10 Meter Walk Test [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Ambulatory Function
  • Knee Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement- Lower Limb Strength
  • Berg Balance Assessment [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Balance Function
  • Grip Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Grip Strength
  • Waist-to-Hip Ratio [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement
  • Body Mass Index [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement
  • Stroke Impact Scale [ Time Frame: 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.
  • Fugl-Meyer Lower Extremity Score [ Time Frame: 6-months post-exercise intervention ]
    Impairment Measurement (see description above)
  • Fugl-Meyer Upper Extremity Score [ Time Frame: 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 [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Depression Measurement
  • Simple and Choice Reaction Time Test [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement
  • Trail Making Test - A & B [ Time Frame: 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) [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement
  • Fasting Blood Draws [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Biological Biomarker
Original Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2018)
  • 6 Minute Walk Test / 10 Meter Walk Test [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Ambulatory Function
  • Knee Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement- Lower Limb Strength
  • Berg Balance Assessment [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Balance Function
  • Grip Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Grip Strength
  • Waist-to-Hip Ratio [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement
  • Body Mass Index [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement
  • Stroke Impact Scale [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Functional Measurement
  • Fugl-Meyer Lower Extremity Score [ Time Frame: 6-months post-exercise intervention ]
    Impairment Measurement
  • Fugl-Meyer Upper Extremity Score [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Impairment Measurement
  • Patient Health Questionnaire (PHQ)-9 [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Depression Measurement
  • Simple and Choice Reaction Time Test [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement
  • Trail Making Test - A & B [ Time Frame: 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) [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement
  • Fasting Blood Draws [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Biological Biomarker
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fluoxetine Opens Window to Improve Motor Recovery After Stroke
Official Title  ICMJE FLOW Trial: Fluoxetine to Open the Critical Period Time Window to Improve Motor Recovery After Stroke
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Stroke
  • Cerebrovascular Accident
  • Cerebral Infarction
  • Brain Infarction
  • Brain Ischemia
  • Cerebrovascular Disorders
  • Brain Diseases
  • Central Nervous System Diseases
  • Nervous System Diseases
  • Vascular Diseases
Intervention  ICMJE
  • Drug: Fluoxetine Hydrochloride
    Half of the participants will take fluoxetine for a period of 15-17 weeks (depending on ramp-up period).
    Other Name: Prozac
  • Other: Placebo
    Half of the participants will take the a placebo for a period of 15-17 weeks (depending on ramp-up period).
    Other Name: "Sugar" Pill
  • Behavioral: Exercise Program
    All participants will take part in a 12-week exercise program. The program will run 3 times/week, 1 hour/class.
Study Arms  ICMJE
  • Experimental: 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).
    Interventions:
    • Drug: Fluoxetine Hydrochloride
    • Behavioral: Exercise Program
  • Placebo Comparator: 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).
    Interventions:
    • Other: Placebo
    • Behavioral: Exercise Program
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 21, 2018)
176
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2020
Estimated Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Josie Chundamala, MA, CCRP 416-597-3422 ext 7229 josie.chundamala@uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03448159
Other Study ID Numbers  ICMJE CTO #1465
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Unused blood samples will be processed and centrally stored in cryovials in a minus 80 degrees freezer for future analyses under the supervision of Study Investigator, Dr. Sandra Black (Sunnybrook, M6 West, 2075 Bayview Avenue, Toronto). The intent is to make the stored frozen cryovials available to all Heart and Stroke Foundation Canadian Partnership of Stroke Recovery (CPSR) investigators to apply for access, but it is currently undecided if other researchers will be allowed to apply for access to the samples. Access will be controlled by a Subcommittee of CPSR Investigators who will review and approve requests and oversee access to the biobank. Stored cryovials will remain at Sunnybrook under the supervision of Dr. Sandra Black for a period of up to 10 years.
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: Mark Bayley, MD University Health Network, Toronto
Principal Investigator: Courtney Pollock, PhD University of British Columbia & GF Strong Rehab Centre
Principal Investigator: Bradley MacIntosh, PhD Sunnybrook Health Sciences Centre
Principal Investigator: Sean Dukelow, MD University of Calgary
Principal Investigator: Sepideh Pooyania, MD Riverview Health Centre
Principal Investigator: Michelle Ploughman, PhD Memorial University of Newfoundland
Principal Investigator: Marilyn Mackay-Lyons, PhD Dalhousie University
Principal Investigator: Robert Teasell, MD Parkwood Institute
PRS Account University Health Network, Toronto
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP