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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01719042
Recruitment Status : Withdrawn (No recruitment was achievable)
First Posted : November 1, 2012
Last Update Posted : April 4, 2013
Information provided by (Responsible Party):
University of Florida

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Mycobacterium Avium Complex Adverse Effects Drug: Zofran (8mg) Dietary Supplement: Ensure Phase 2

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  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Improving Tolerance of Treatment of Pulmonary Mycobacterium Avium Complex Infections
Study Start Date : January 2013
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

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 Name: 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 Name: Ensure Plus

Primary Outcome Measures :
  1. Change in Gastroparesis Cardinal Symptom Index Score [ Time Frame: Change from baseline at the end of nine weeks ]
    A survey instrument used to assess the severity of patient-reported gastrointestinal symptoms in clinical trials

Secondary Outcome Measures :
  1. Leptin [ Time Frame: Baseline ]
    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

Other Outcome Measures:
  1. Change in QTc on Electrocardiogram greater than 500 milliseconds [ Time Frame: Change from baseline at the end of nine weeks ]
    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01719042

Sponsors and Collaborators
University of Florida
Principal Investigator: Kevin P Fennelly, MD, MPH University of Florida

Responsible Party: University of Florida Identifier: NCT01719042     History of Changes
Other Study ID Numbers: 187-2012
First Posted: November 1, 2012    Key Record Dates
Last Update Posted: April 4, 2013
Last Verified: April 2013

Additional relevant MeSH terms:
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Nontuberculous
Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents