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

• ClinicalTrials.gov Identifier: NCT03728153
• Recruitment Status: Not yet recruiting
• First Posted: November 1, 2018
• Last Update Posted: June 5, 2019
• Sponsor: Massachusetts General Hospital
• Collaborator: Muhimbili University of Health and Allied Sciences
• Information provided by (Responsible Party): Farrah Mateen, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Stroke; Stroke, Ischemic	Drug: Fluoxetine 20 MG Oral Tablet	Phase 2

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 14 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. 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, evaluate participant mRS, and inquire about tolerability issues. Completion of the 90-day visit and associated assessments is considered the study endpoint.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Phase II study of one dose
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MAMBO: Measuring Ambulation, Motor, and Behavioral Outcomes With Post-Stroke Fluoxetine in Tanzania
• Estimated Study Start Date: September 1, 2019
• Estimated Primary Completion Date: February 29, 2020
• Estimated Study Completion Date: October 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: 20mg dose; Fluoxetine 20 MG Oral Tablet	Drug: Fluoxetine 20 MG Oral Tablet; Once-daily dosing for 90 days; Other Name: Prozac 20 MG Oral Tablet

Outcome Measures

Primary Outcome Measures :

1. Serum sodium or elevation of hepatic enzyme (ALT) [ Time Frame: 30 days following acute, ischemic stroke ]
   hyponatremia (<125 mmol/L); hepatic impairment as defined by a serum alanine aminotransferase (ALT) of >120 U/L,
2. Serum sodium or elevation of hepatic enzyme (ALT) [ Time Frame: 60 days following acute, ischemic stroke ]
   hyponatremia (<125 mmol/L); hepatic impairment as defined by a serum alanine aminotransferase (ALT) of >120 U/L,
3. Serum sodium or elevation of hepatic enzyme (ALT) [ Time Frame: 90 days following acute, ischemic stroke ]
   hyponatremia (<125 mmol/L); hepatic impairment as defined by a serum alanine aminotransferase (ALT) of >120 U/L,

Secondary Outcome Measures :

1. Fugl-Meyer Motor Scale Score for assessment of motor function after stroke [ Time Frame: 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.
2. Montgomery-Asberg Depression Rating Scale [ Time Frame: 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.
3. modified Rankin Scale [ Time Frame: <14 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.
4. modified Rankin Scale [ Time Frame: 30 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.
5. modified Rankin Scale [ Time Frame: 60 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.
6. modified Rankin Scale [ Time Frame: 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.
7. The PHQ-9 scale for measuring depression [ Time Frame: 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

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Participant is 18 years of age or older
2. Participant has experienced a CT-confirmed ischemic stroke w/in 14 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.

Contacts and Locations

Contacts

Contact: Farrah J Mateen, MD, PhD; 6177264540; fmateen@partners.org

Contact: Andre C Vogel, BA; 6177264540; avogel@partners.org

Sponsors and Collaborators

Massachusetts General Hospital

Muhimbili University of Health and Allied Sciences

Investigators

• Principal Investigator: Farrah J Mateen, MD, PhD; Massachusetts General Hospital

More Information

Publications:

GBD 2015 Neurological Disorders Collaborator Group. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. 2017 Nov;16(11):877-897. doi: 10.1016/S1474-4422(17)30299-5. Epub 2017 Sep 17.

Walker RW, Viney R, Green L, Mawanswila M, Maro VP, Gjertsen C, Godfrey H, Smailes R, Gray WK. Trends in stroke admissions to a Tanzanian hospital over four decades: a retrospective audit. Trop Med Int Health. 2015 Oct;20(10):1290-6. doi: 10.1111/tmi.12547. Epub 2015 Jun 1.

Stenumgård PS, Rakotondranaivo MJ, Sletvold O, Follestad T, Ellekjær H. Stroke in a resource-constrained hospital in Madagascar. BMC Res Notes. 2017 Jul 24;10(1):307. doi: 10.1186/s13104-017-2627-4.

Seremwe F, Kaseke F, Chikwanha TM, Chikwasha V. Factors associated with hospital arrival time after the onset of stroke symptoms: A cross-sectional study at two teaching hospitals in Harare, Zimbabwe. Malawi Med J. 2017 Jun;29(2):171-176.

Baatiema L, Chan CKY, Sav A, Somerset S. Interventions for acute stroke management in Africa: a systematic review of the evidence. Syst Rev. 2017 Oct 24;6(1):213. doi: 10.1186/s13643-017-0594-4. Review.

Okeng'o K, Chillo P, Gray WK, Walker RW, Matuja W. Early Mortality and Associated Factors among Patients with Stroke Admitted to a Large Teaching Hospital in Tanzania. J Stroke Cerebrovasc Dis. 2017 Apr;26(4):871-878. doi: 10.1016/j.jstrokecerebrovasdis.2016.10.037. Epub 2016 Nov 29.

Ezejimofor MC, Uthman OA, Maduka O, Ezeabasili AC, Onwuchekwa AC, Ezejimofor BC, Asuquo E, Chen YF, Stranges S, Kandala NB. Stroke survivors in Nigeria: A door-to-door prevalence survey from the Niger Delta region. J Neurol Sci. 2017 Jan 15;372:262-269. doi: 10.1016/j.jns.2016.11.059. Epub 2016 Nov 25.

Fugl-Meyer AR, Jääskö L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13.

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9.

• Responsible Party: Farrah Mateen, Associate Professor, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03728153 History of Changes
• Other Study ID Numbers: 2018P001693
• First Posted: November 1, 2018
• Last Update Posted: June 5, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Contingent upon the requirements of the Tanzanian National Medical Institute for Research

• 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

Keywords provided by Farrah Mateen, Massachusetts General Hospital:

Motor recovery

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Fluoxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors