Clinical trial NCT03728153: Measuring Ambulation, Motor, and Behavioral Outcomes With Post-Stroke Fluoxetine in Tanzania
Official title: MAMBO: Measuring Ambulation, Motor, and Behavioral Outcomes With Post-Stroke Fluoxetine in Tanzania
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Stroke
Stroke, Ischemic
Keywords: Motor recovery
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Muhimbili University of Health and Allied Sciences
First posted: 2018-11-01
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase II study of one dose
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Serum Sodium Concentration
timeFrame: 90 days following acute, ischemic stroke
measure: Serum Alanine Aminotransferase (ALT)
timeFrame: 90 days
Secondary outcomes:
measure: Fugl-Meyer Motor Scale Score for Assessment of Motor Function After Stroke
timeFrame: 90 days following acute, ischemic stroke
measure: Montgomery-Asberg Depression Rating Scale
timeFrame: 90 days following acute, ischemic stroke
measure: Modified Rankin Scale
timeFrame: 90 days following acute, ischemic stroke
measure: The Patient Health Questionnaire-9 (PHQ-9) Scale for Measuring Depression
timeFrame: 90 days following acute ischemic stroke
Other outcomes:
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili National Hospital
Study officials:
affiliation: Massachusetts General Hospital
name: Farrah J Mateen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vogel AC, Okeng'o K, Chiwanga F, Ismail SS, Buma D, Pothier L, Mateen FJ. MAMBO: Measuring ambulation, motor, and behavioral outcomes with post-stroke fluoxetine in Tanzania: Protocol of a phase II clinical trial. J Neurol Sci. 2020 Jan 15;408:116563. doi: 10.1016/j.jns.2019.116563. Epub 2019 Nov 6.