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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

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.

Condition or disease Intervention/treatment Phase
Stroke Cerebrovascular Accident Cerebral Infarction Brain Infarction Brain Ischemia Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Drug: Fluoxetine Hydrochloride Other: Placebo Behavioral: Exercise Program Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
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
Official Title: FLOW Trial: Fluoxetine to Open the Critical Period Time Window to Improve Motor Recovery After Stroke
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).
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

Behavioral: Exercise Program
All participants will take part in a 12-week exercise program. The program will run 3 times/week, 1 hour/class.

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).
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Knee Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement- Lower Limb Strength

  3. Berg Balance Assessment [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Balance Function

  4. Grip Strength [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Grip Strength

  5. Waist-to-Hip Ratio [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement

  6. Body Mass Index [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Physical Measurement - Health Measurement

  7. 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.

  8. Fugl-Meyer Lower Extremity Score [ Time Frame: 6-months post-exercise intervention ]
    Impairment Measurement (see description above)

  9. 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.

  10. Patient Health Questionnaire (PHQ)-9 [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Depression Measurement

  11. Simple and Choice Reaction Time Test [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement

  12. Trail Making Test - A & B [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Cognitive Measurement

  13. 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

  14. Fasting Blood Draws [ Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention ]
    Biological Biomarker



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03448159


Contacts
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Contact: Josie Chundamala, MA, CCRP 416-597-3422 ext 7229 josie.chundamala@uhn.ca

Locations
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Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Nick Cunningham    403-944-4050    nick.cunningham@ucalgary.ca   
Principal Investigator: Sean Dukelow, MD         
Canada, British Columbia
University of British Columbia & GF Strong Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 2G9
Contact: Courtney Pollock    604-827-1631    courtney.pollock@ubc.ca   
Principal Investigator: Courtney Pollock, PhD         
Canada, Manitoba
Riverview Health Centre Recruiting
Winnipeg, Manitoba, Canada, R3L 2P4
Contact: Sepideh Pooyania    204-478-6219    spooyania@rhc.mb.ca   
Principal Investigator: Sepideh Pooyania, MD         
Canada, Newfoundland and Labrador
Memorial University of Newfoundland Recruiting
St. John's, Newfoundland and Labrador, Canada, A1A 1E5
Contact: Marie Curtis    709-777-2082    marie.curtis@mun.ca   
Principal Investigator: Michelle Ploughman, PhD         
Canada, Nova Scotia
Dalhousie University Recruiting
Halifax, Nova Scotia, Canada, B3H 3J5
Contact: Melanie Dunlop    902-473-1401    Melanie.Dunlop@nshealth.ca   
Principal Investigator: Marilyn Mackay-Lyons, PhD         
Canada, Ontario
Parkwood Institute Recruiting
London, Ontario, Canada, N6C 0A7
Contact: Mitch Longval    519-646-6100 ext 42739    Mitch.longval@sjhc.london.on.ca   
Principal Investigator: Robert Teasell, MD         
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Ellen Cohen    416-480-6100 ext 85406    ecohen@sri.utoroton.ca   
Principal Investigator: Bradley MacIntosh, PhD         
Toronto Rehabilitation Institute - University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2A2
Contact: Evan Foster    416-597-3422 ext 3362    Evan.Foster@uhn.ca   
Principal Investigator: Mark Bayley, MD         
Sponsors and Collaborators
University Health Network, Toronto
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
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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

Additional Information:
Publications:

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03448159     History of Changes
Other Study ID Numbers: CTO #1465
First Posted: February 27, 2018    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
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.

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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
Keywords provided by University Health Network, Toronto:
Stroke
Exercise
Fluoxetine
Randomized Control Trial
Rehabilitation
Additional relevant MeSH terms:
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Stroke
Cerebral Infarction
Brain Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Brain Ischemia
Brain Infarction
Vascular Diseases
Infarction
Nervous System Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
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