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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke, Ischemic; Acute Stroke
• Intervention / Treatment: Drug: Fluoxetine 20 MG Oral Tablet

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania
    • Muhimbili National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 20mg dose; Fluoxetine 20 MG Oral Tablet	Drug: Fluoxetine 20 MG Oral Tablet; Once-daily dosing for 90 days; Other Names: Prozac 20 MG Oral Tablet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Muhimbili University of Health and Allied Sciences
• Investigators: Principal Investigator: Farrah J Mateen, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2019
• Primary Completion (Actual): January 6, 2021
• Study Completion (Actual): January 6, 2021

Study Registration Dates

• First Submitted: October 29, 2018
• First Submitted That Met QC Criteria: October 30, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 2, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Motor recovery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: 2018P001693

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Contingent upon the requirements of the Tanzanian National Medical Institute for Research

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes