Measuring Ambulation, Motor, and Behavioral Outcomes With Post-Stroke Fluoxetine in Tanzania

Study Overview
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Brief Summary
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This is a phase II, randomized study of 120 adults age 18 or above who will prescribed 20mg daily Fluoxetine for 90 days following acute, ischemic stroke.

Detailed Description
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This is a prospective, phase II study of fluoxetine for motor recovery post-stroke in adults with new-onset ischemic stroke in urban Tanzania. Participants will be enrolled at the Muhimbili National Hospital (MNH) in Dar Es Salaam after confirmation of exclusion and inclusion criteria, including a head CT. Participants will be enrolled within 21 days of acute, ischemic stroke. The study will utilize a novel method for monitoring patient medication adherence: electronic pill bottles that can record medication use events. The primary goals of this study are to assess the safety and tolerability of fluoxetine post-stroke to evaluate the feasibility of conducting a larger, phase III study in the future. Vital status will be monitored throughout the study's enrollment period. At enrollment, participants will have cognitive tests administered, receive lumbar puncture, and receive an MRI brain. After discharge from the hospital, participants will be seen at 30-, 60-, and 90-days post-enrollment for an in-person study visit. At each time point, investigators will draw 10-15 mL of blood; download medication adherence data from participants' electronic pill bottles; and inquire about adverse events and evaluate patient disability through the modified Rankin Scale. If participants stop taking their daily pill, stroke specific reasons for non-adherence will be inquired including dysphagia, self-administration, and other concerns. Primary assessments will be for safety and tolerability, as well as measurement of the Fugl-Meyer Motor Scale. Medication use data will also be collected through the electronic pill bottle, which will be returned to study investigators. As secondary assessments, the PHQ-9, and the Asberg Depressive Symptom Questionnaire will be administered. All 90-day assessments will be administered by senior site investigators, who will take a final 10-15mL blood draw to test for serum sodium and liver enzymes, possible adverse events related to long-term fluoxetine use, conduct a second MRI brain, evaluate participant mRS, and inquire about tolerability issues. Completion of the 90-day visit and associated assessments is considered the study endpoint.

Official Title
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MAMBO: Measuring Ambulation, Motor, and Behavioral Outcomes With Post-Stroke Fluoxetine in Tanzania

Conditions
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Acute Stroke, Stroke, Ischemic

Intervention / Treatment
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* Drug: Fluoxetine 20 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is 18 years of age or older Participant has experienced a CT-confirmed ischemic stroke w/in 21 days of enrollment Exclusion Criteria: NIH Stroke Scale Score >20 points Unconscious at presentation Hemorrhagic conversion of ischemic infarct transient ischemic symptoms <24h, Current antidepressant or psychoactive drug use (e.g. SSRI, monoxidase amine inhibitor, benzodiazepine). Current pregnancy. History of recent head trauma. Baseline motor deficits from other etiologies including prior stroke. Dysphagia preventing the swallowing of a pill. Hyponatremia (<125 mmol/L), hepatic impairment as defined by a serum alanine aminotransferase (ALT) of >120 U/L. Renal impairment as defined by a creatinine >180 micromol/L or GFR <30mL/min/1.73m2. Patients who are moribund for other reasons and unlikely to survive to 90 days will also be excluded from participation. Contraindication to MRI (e.g. piercings/tattoos, electronic/metallic implants, claustrophobia) Contraindication to lumbar puncture (e.g. infection at site of needle insertion, evidence of elevated ICP, coagulopathy/thrombocytopenia or use of therapeutic anticoagulation, or a history of LP complications).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Phase II study of one dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20mg dose<br>Fluoxetine 20 MG Oral Tablet | Drug: Fluoxetine 20 MG Oral Tablet<br>* Once-daily dosing for 90 days<br>* Other names: Prozac 20 MG Oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Sodium Concentration | Serum Sodium Concentration was measured in mmol/L. Hyponatremia was considered as <125 mmol/L. | 90 days following acute, ischemic stroke | 
| Serum Alanine Aminotransferase (ALT) | Hepatic impairment was measured by elevation of hepatic enzyme (serum alanine aminotransferase; ALT) of >120 U/L | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Motor Scale Score for Assessment of Motor Function After Stroke | The Fugl Meyer motor scale is used to assess post-stroke motor recovery in stroke patients. It is scored on a scale from 0 to 100, with lower scores indicating greater disability. It evaluates both lower and upper extremities for motor performance: 66 points are allocated to the upper extremities, 34 to the lower extremities. The two extremities are summed to achieve the total score. | 90 days following acute, ischemic stroke | 
| Montgomery-Asberg Depression Rating Scale | 10-item questionnaire used to evaluate the severity of a patient's depressive symptoms. Each item is scored on a scale from 0 to 6, the scores are summed, and the total score (0 to 60 points) is reported. The greater the score, the more severe the degree of depression. | 90 days following acute, ischemic stroke | 
| Modified Rankin Scale | Validated instrument for measuring the degree of disability in stroke patients. The modified Rankin Scale is based on a physicians subjective evaluation. The scale ranges from 0, indicating perfect health, to 6, indicating that the patient is dead. | 90 days following acute, ischemic stroke | 
| The Patient Health Questionnaire-9 (PHQ-9) Scale for Measuring Depression | The PHQ-9 is a validated 9-point questionnaire for measuring depression symptom severity. Each question is scored from 0-3. Answers are summed and the total score (0 to 27) is reported. The greater the score, the greater the severity of depression. | 90 days following acute ischemic stroke | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Motor recovery