Fluoxetine Opens Window to Improve Motor Recovery After Stroke

Stroke Clinical Trial

— FLOW  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03448159
• Other study ID #: 18-6002
• Secondary ID: CTO #1465
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2019
• Est. completion date: September 30, 2022

Study information

• Verified date: November 2022
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Infarction
• Brain Ischemia
• Central Nervous System Diseases
• Cerebral Infarction
• Cerebrovascular Accident
• Cerebrovascular Disorders
• Infarction
• Nervous System Diseases
• Stroke
• Vascular Diseases

Intervention

Drug:
• Fluoxetine Hydrochloride
Half of the participants will take fluoxetine for a period of 15-17 weeks (depending on ramp-up period).

Other:
• Placebo
Half of the participants will take the a placebo for a period of 15-17 weeks (depending on ramp-up period).

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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	Parkwood Institute	London	Ontario
Canada	Memorial University of Newfoundland	St. John's	Newfoundland and Labrador
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Rehabilitation Institute - University Health Network	Toronto	Ontario
Canada	University of British Columbia & GF Strong Centre	Vancouver	British Columbia
Canada	Riverview Health Centre	Winnipeg	Manitoba

Sponsors (11)

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

Country where clinical trial is conducted

Canada, 

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* Note: There are 51 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fugl-Meyer Lower Extremity Score	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	6 Minute Walk Test / 10 Meter Walk Test	Physical Measurement - Ambulatory Function	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Knee Strength	Physical Measurement- Lower Limb Strength	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Berg Balance Assessment	Physical Measurement - Balance Function	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Grip Strength	Physical Measurement - Grip Strength	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Waist-to-Hip Ratio	Physical Measurement - Health Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Body Mass Index	Physical Measurement - Health Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Stroke Impact Scale	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
Secondary	Fugl-Meyer Lower Extremity Score	Impairment Measurement (see description above)	6-months post-exercise intervention
Secondary	Fugl-Meyer Upper Extremity Score	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
Secondary	Patient Health Questionnaire (PHQ)-9	Depression Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Simple and Choice Reaction Time Test	Cognitive Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Trail Making Test - A & B	Cognitive Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Montreal Cognitive Assessment (including 5 word recall and clock test)	Cognitive Measurement	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention
Secondary	Fasting Blood Draws	Biological Biomarker	Following completion of the 12-week exercise intervention and 6-months post-exercise intervention

External Links

•   Research breakthrough to revolutionize stroke treatment
•   Tracking Heart Disease and Stroke in Canada