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

This study has been withdrawn prior to enrollment.
(No recruitment was achievable)
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01719042
First received: October 22, 2012
Last updated: April 2, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Mycobacterium Avium Complex
Adverse Effects
Drug: Zofran (8mg)
Dietary Supplement: Ensure
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Improving Tolerance of Treatment of Pulmonary Mycobacterium Avium Complex Infections

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Change in Gastroparesis Cardinal Symptom Index Score [ Time Frame: Change from baseline at the end of nine weeks ] [ Designated as safety issue: No ]
    A survey instrument used to assess the severity of patient-reported gastrointestinal symptoms in clinical trials


Secondary Outcome Measures:
  • Leptin [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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:
  • Change in QTc on Electrocardiogram greater than 500 milliseconds [ Time Frame: Change from baseline at the end of nine weeks ] [ Designated as safety issue: Yes ]
    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


Enrollment: 0
Study Start Date: January 2013
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01719042

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

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01719042     History of Changes
Other Study ID Numbers: 187-2012
Study First Received: October 22, 2012
Last Updated: April 2, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Atypical
Anti-Bacterial Agents
Ondansetron
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Antipruritics
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

ClinicalTrials.gov processed this record on July 24, 2014