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

Stroke, Ischemic Clinical Trial

— MAMBO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03728153
• Other study ID #: 2018P001693
• Status: Completed
• Phase: Phase 2
• Start date: November 26, 2019
• Est. completion date: January 6, 2021

Study information

• Verified date: May 2022
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 6, 2021
• Est. primary completion date: January 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Stroke
• Ischemic Stroke
• Stroke
• Stroke, Ischemic

Intervention

Drug:
• Fluoxetine 20 MG Oral Tablet
Once-daily dosing for 90 days

Locations

Country	Name	City	State
Tanzania	Muhimbili National Hospital	Dar es Salaam

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Muhimbili University of Health and Allied Sciences

Country where clinical trial is conducted

Tanzania, 

References & Publications (1)

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. — View Citation

Outcome

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