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

University Health Network, Toronto

Status and phase: Completed; Phase 2

Conditions: Brain Ischemia; Cerebrovascular Accident; Cerebral Infarction; Stroke; Brain Infarction; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases

Treatments: Behavioral: Exercise Program; Other: Placebo; Drug: Fluoxetine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03448159

18-6002

CTO #1465

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: 25+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

Fluoxetine Hydrochloride

Experimental group

Description:

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).

Treatment:

Behavioral: Exercise Program

Drug: Fluoxetine Hydrochloride

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Behavioral: Exercise Program

Other: Placebo