Improving Tolerance of Treatment of Pulmonary MAC Infections (ITT-MAC)

Improving Tolerance of Treatment of Pulmonary Mycobacterium Avium Complex Infections

The purpose of this study is to improve tolerance of treatment of pulmonary Mycobacterium avium Complex disease via the use of therapeutic drug monitoring and the addition of anti-nausea medication or dietary supplements to the patients' daily drug regimen. The aims of this study are to use (1) Zofran® (Ondansetron 8mg), an anti-nausea medication or (2) a dietary supplement to decrease medication related gastrointestinal side effects of medications used to treat Mycobacterium avium Complex.

Study Overview

• Status: Withdrawn
• Conditions: Adverse Effects; Mycobacterium Avium Complex
• Intervention / Treatment: Drug: Zofran (8mg); Dietary supplement: Ensure

Detailed Description

As part of this study, investigators will review medical records to be sure that the patient meets the required criteria and is healthy enough to take part in this study.

The study will consist of five separate visits to the Clinical research Center at the University of Florida and each visit will last anywhere from 6-8 hours. Patients will be given a diary of questionnaires where they will record when they take their medication and any side effects they might have. Patients will also have Electrocardiograms (ECGs) to make sure they are healthy enough to be a participant in the study and to measure the effects of their medication on their heart. During this study, patients will continue treatment of their Mycobacterium avium Complex infections. Patients will be observed taking their medication on each of the five separate days. On each of these days patients will have blood drawn at 2 and 6 hours after their drugs are taken in order to measure drug levels in their blood. We will also use this blood to measure levels of proteins and hormones and to make sure the medications are not affecting the patient's heart. The patient will fill out several questionnaires and do a dietary assessment online. Investigators will assess the patient's body make-up using a device called the Bod Pod. The patient will also be assigned to one of two treatment groups: (1) Ondansetron 8mg (Zofran®, GlaxoSmithKline, Research Triangle Park, NC) every morning before breakfast versus (2) a dietary supplement prior to taking daily medication. The patient will be assigned to the first treatment group for a period of two weeks. On the third study visit investigators will switch the patient to the second group.

Although the incidence of tuberculosis has decreased in the United States over the last few decades, the incidence of chronic pulmonary infections with nontuberculous mycobacteria (NTM) appears to be increasing. Unfortunately, a common problem in the management of these infections is the inability of elderly patients to tolerate the currently recommended multidrug regimen of (1) azithromycin or clarithromycin, (2) rifampin or rifabutin, and (3) ethambutol. The most frequent adverse reactions of MAC treatment are gastrointestinal (GI), most commonly associated with the macrolides and rifampin. Although macrolide toxicity is generally dose-related, the role of routine monitoring of drug concentrations and subsequent dose adjustment has not been studied. The role of anti-emetics or dietary supplements to mitigate these symptoms is also not defined.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Physician diagnosis of Mycobacterium avium Complex with nodular bronchiectasis
• On daily treatment for Mycobacterium avium Complex consisting of 250mg of Azithromycin, 600mg of Rifampin, and 15mg/kg of Ethambutol
• Experiencing gastrointestinal symptoms due to their multi-drug treatment regimen
• Has access to the internet

Exclusion Criteria:

• Claustrophobia
• Currently smokes cigarettes
• Persons with disseminated Mycobacterium avium Complex infections
• Persons with a known and diagnosed immunosuppressive disorder (i.e. cancer, HIV)
• Persons with physician diagnosed Irritable Bowel Syndrome, Crohn's Disease, or Ulcerative Colitis
• Persons with moderate to severe kidney or liver dysfunction
• Persons who are co-colonized with an NTM aside from Mycobacterium avium Complex
• Persons who initially present with a prolonged QT interval (defined as greater 500 milliseconds) on any baseline ECG
• Previous adverse reaction or allergy to Zofran (Ondansetron)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Zofran (8mg); Participant will take Zofran (8mg) once per day before taking their antibiotic regimen	Drug: Zofran (8mg); Subject will take 8mg of Zofran before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks; Other Names: Ondansetron
ACTIVE_COMPARATOR: Ensure; Subject will drink a can of Ensure before taking their antibiotic regimen	Dietary supplement: Ensure; Subject will drink one cam of Ensure before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks; Other Names: Ensure Plus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gastroparesis Cardinal Symptom Index Score	A survey instrument used to assess the severity of patient-reported gastrointestinal symptoms in clinical trials	Change from baseline at the end of nine weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leptin	Leptin is a natural hormone produced by your body's fat cells and acts as a signal which tells your brain you are no longer hungry	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QTc on Electrocardiogram greater than 500 milliseconds	To determine if the drug-drug interaction of azithromycin and Zofran (ondansetron) causes significant prolongation of the corrected QT (QTc) interval in this population of older female patients	Change from baseline at the end of nine weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Kevin P Fennelly, MD, MPH, University of Florida

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (ESTIMATE): November 1, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 4, 2013
• Last Update Submitted That Met QC Criteria: April 2, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Mycobacterium avium-intracellulare Infection; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Ondansetron
• Other Study ID Numbers: 187-2012