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

November 1, 2022 updated by: University Health Network, Toronto

FLOW Trial: Fluoxetine to Open the Critical Period Time Window to Improve Motor Recovery After Stroke

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • University of Calgary
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 2G9
        • University of British Columbia & GF Strong Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3L 2P4
        • Riverview Health Centre
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1A 1E5
        • Memorial University of Newfoundland
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3J5
        • Dalhousie University
    • Ontario
      • London, Ontario, Canada, N6C 0A7
        • Parkwood Institute
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 2A2
        • Toronto Rehabilitation Institute - University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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).
Behavioral: Exercise Program
All participants will take part in a 12-week exercise program. The program will run 3 times/week, 1 hour/class.
Other: Placebo
Half of the participants will take the a placebo for a period of 15-17 weeks (depending on ramp-up period).
Other Names:
  • "Sugar" Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Following completion of the 12-week exercise intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Knee Strength
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Physical Measurement- Lower Limb Strength
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Berg Balance Assessment
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Physical Measurement - Balance Function
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Grip Strength
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Physical Measurement - Grip Strength
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Waist-to-Hip Ratio
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Physical Measurement - Health Measurement
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Body Mass Index
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Physical Measurement - Health Measurement
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
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.
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Fugl-Meyer Lower Extremity Score
Time Frame: 6-months post-exercise intervention
Impairment Measurement (see description above)
6-months post-exercise intervention
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.
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Patient Health Questionnaire (PHQ)-9
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Depression Measurement
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Simple and Choice Reaction Time Test
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Cognitive Measurement
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Trail Making Test - A & B
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Cognitive Measurement
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
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
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Fasting Blood Draws
Time Frame: Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Biological Biomarker
Following completion of the 12-week exercise intervention and 6-months post-exercise intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Sunnybrook Health Sciences Centre
University of British Columbia
University of Calgary
Dalhousie University
Memorial University of Newfoundland
Applied Health Research Centre
Parkwood Hospital, London, Ontario
Brain Canada
Riverview Health Centre Foundation
Heart and Stroke Foundation Canadian Partnership for Stroke Recovery

Investigators

  • 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: Robert Teasell, MD, Parkwood Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Actual)

September 30, 2022

Study Completion (Actual)

September 30, 2022

Study Registration Dates

First Submitted

February 21, 2018

First Submitted That Met QC Criteria

February 21, 2018

First Posted (Actual)

February 27, 2018

Study Record Updates

Last Update Posted (Actual)

November 4, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-6002
  • CTO #1465 (Other Identifier: Clinical Trials Ontario)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD 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.

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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