Acute Stroke, Stroke, Ischemic
Conditions
Keywords
Motor recovery
Brief summary
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
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.
Interventions
DRUGFluoxetine 20 MG Oral Tablet
Once-daily dosing for 90 days
Sponsors
Muhimbili University of Health and Allied Sciences
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase II study of one dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Participant is 18 years of age or older 2. Participant has experienced a CT-confirmed ischemic stroke w/in 21 days of enrollment
Exclusion criteria
1. NIH Stroke Scale Score \>20 points 2. Unconscious at presentation 3. Hemorrhagic conversion of ischemic infarct 4. transient ischemic symptoms \<24h, 5. Current antidepressant or psychoactive drug use (e.g. SSRI, monoxidase amine inhibitor, benzodiazepine). 6. Current pregnancy. 7. History of recent head trauma. 8. Baseline motor deficits from other etiologies including prior stroke. 9. Dysphagia preventing the swallowing of a pill. 10. Hyponatremia (\<125 mmol/L), hepatic impairment as defined by a serum alanine aminotransferase (ALT) of \>120 U/L. 11. Renal impairment as defined by a creatinine \>180 micromol/L or GFR \<30mL/min/1.73m2. 12. Patients who are moribund for other reasons and unlikely to survive to 90 days will also be excluded from participation. 13. Contraindication to MRI (e.g. piercings/tattoos, electronic/metallic implants, claustrophobia) 14. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Sodium Concentration | 90 days following acute, ischemic stroke | Serum Sodium Concentration was measured in mmol/L. Hyponatremia was considered as \<125 mmol/L. |
| Serum Alanine Aminotransferase (ALT) | 90 days | Hepatic impairment was measured by elevation of hepatic enzyme (serum alanine aminotransferase; ALT) of \>120 U/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fugl-Meyer Motor Scale Score for Assessment of Motor Function After Stroke | 90 days following acute, ischemic 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. |
| Montgomery-Asberg Depression Rating Scale | 90 days following acute, ischemic stroke | 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. |
| Modified Rankin Scale | 90 days following acute, ischemic stroke | 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. |
| The Patient Health Questionnaire-9 (PHQ-9) Scale for Measuring Depression | 90 days following acute ischemic stroke | 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. |
Countries
Tanzania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 20mg Dose Fluoxetine 20 MG Oral Tablet
Fluoxetine 20 MG Oral Tablet: Once-daily dosing for 90 days | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | 20mg Dose |
|---|---|
| Age, Continuous | 52 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Tanzania | 34 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 34 |
| other Total, other adverse events | 2 / 34 |
| serious Total, serious adverse events | 8 / 34 |
Outcome results
Primary
Serum Alanine Aminotransferase (ALT)
Hepatic impairment was measured by elevation of hepatic enzyme (serum alanine aminotransferase; ALT) of \>120 U/L
Time frame: 90 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 20mg Dose | Serum Alanine Aminotransferase (ALT) | 28 U/L |
Primary
Serum Sodium Concentration
Serum Sodium Concentration was measured in mmol/L. Hyponatremia was considered as \<125 mmol/L.
Time frame: 90 days following acute, ischemic stroke
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20mg Dose | Serum Sodium Concentration | 138.7 mmol/L | Standard Deviation 2.9 |
Secondary
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.
Time frame: 90 days following acute, ischemic stroke
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20mg Dose | Fugl-Meyer Motor Scale Score for Assessment of Motor Function After Stroke | 62.7 score on a scale | Standard Deviation 28.1 |
Secondary
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.
Time frame: 90 days following acute, ischemic stroke
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 20mg Dose | Modified Rankin Scale | 2 score on a scale |
Secondary
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.
Time frame: 90 days following acute, ischemic stroke
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20mg Dose | Montgomery-Asberg Depression Rating Scale | 5.6 units on a scale | Standard Deviation 5.5 |
Secondary
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.
Time frame: 90 days following acute ischemic stroke
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20mg Dose | The Patient Health Questionnaire-9 (PHQ-9) Scale for Measuring Depression | 4.6 units on a scale | Standard Deviation 4.1 |