Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Information source: University of Florida
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Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Gastroparesis
Intervention: Erythromycin (Drug); Azithromycin (Drug)
Phase: Phase 2
Sponsored by: University of Florida
Official(s) and/or principal investigator(s):
Baharak Moshiree, MD, Principal Investigator, Affiliation: University of Florida
Erythromycin is effectively used in the treatment of Gastroparesis (GP) patients. In
susceptible patients however, it has been associated with sudden cardiac death due to
prolongation of QT intervals and subsequent cardiac risks through its interaction some other
drugs. Azithromycin (AZI) is a macrolide antibiotic but does not have the mentioned druf
interactions , has fewer gastrointestinal side effects, and fewer risks of QT prolongation
and cardiac arrhythmias. Consequently, AZI avoids drawbacks of dosing with erythromycin and
may be preferred as a prokinetic agent in patients on other concomitant medications.
We hope to demonstrate the effectiveness of Azithromycin (AZI) as compared to Erythromycin
in the treatment of Gastroparesis (GP), and later, form the framework for larger
randomized-controlled parallel studies to investigate use of AZI for treatment of GP.
Our novel hypothesis is to determine whether AZI can be used to treat GP.
Official title: Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Time in Minutes for 50% of the Ingested Meal to Empty the Stomach With a Standardized Breath Test: Half the of the Week 11 Value (Period 2) Less Half the of the Week 4 Value (Period 1). This Estimates the Effect Size.
Gastroparesis Cardinal Symptom Index (GCSI) Score
TLAG (Time From Ingestion of Meal to Start of Gastric Emptying)
Change in Time to 50% Gastric Emptying: Post Test Less Baseline Pooled Over Orderings
Change in Time to 50% Emptying: Post Test Less Baseline Pooled Over Orderings
Gastroparesis Cardinal Symptom Index (GCSI) Score Change From Baseline to Post Treatment
Does GCSI Score Improve (Lower) on Treatment, Pooling the AZ Patients Over Their Treatment Periods? Endpoint is Difference in Post-test Less Baseline
Gastroparesis (GP) is a chronic gastrointestinal motility disorder resulting from delayed
transit of gastric contents from the stomach into the duodenum in the absence of mechanical
outlet obstruction. The symptoms of GP are variable but include early satiety, bloating,
nausea, vomiting, and epigastric abdominal pain. Although the true prevalence of the
disorder is unknown, symptoms suggestive of GP are present in 7-15% of the population with
an estimated one-third of diabetic patients in tertiary care settings having abnormal
gastric emptying studies. Yet, despite the significant healthcare and economic costs due to
frequent hospitalization in these patients, treatment of GP is difficult due to the lack of
available treatment options and the often potential side effects of available prokinetic
agents, including cardiac side effects such as QT prolongation, sudden cardiac death, and
torsade de pointes.
One such medication used for treatment of GP is erythromycin. Erythromycin has its
drawbacks. Several reports of cardiac arrhythmias associated with use of either oral or
intravenous (IV) Erythromycin have been reported. This finding sparked our interest in
another macrolide, Azithromycin (AZI), which does not have the drug-drug interactions as
seen with erythromycin and is not metabolized by the CYP3A inhibitors, therefore having
fewer cardiac side effects.
In This study our primary goal is to determine whether AZI can be used to treat GP.
Minimum age: 18 Years.
Maximum age: 65 Years.
- presenting to gastroenterology motility specialty clinics at the University of
Florida (UF), who meet the clinical and radiologic diagnostic criteria for diagnosis
- Any history of mechanical obstruction
- Gastrointestinal malignancy
- Current use of prokinetics such as cisapride, pimozide, or anticholinergic
medication which cannot be discontinued 72 hrs prior to study
- Abnormal upper endoscopy with finding of erosions or ulcerations
- Helicobacter pylori infection in past 6 months
- Recent abdominal surgery < 6 months
- Cardiac history with EKG finding of QTC > 450 done on a screening test
- Detected renal or hepatic dysfunction described as a GFR <10 ml/min and ALT/AST
values > 2 times the normal level in our laboratory
- Allergy to macrolide antibiotics
- Psychiatric history other than anxiety or depression
- Predominant symptoms of irritable bowel syndrome such as constipation or diarrhea
- Uncontrolled diabetes with fasting blood glucose levels > 180 mg/dL, due to effect of
hyperglycemia on gastric emptying. For patients with diabetes, blood glucose levels
will be recorded in a patient diary.
- Pregnant or nursing females
- Any history of myasthenia gravis
- Current use of Coumadin, lovastatin, simvastatin Nelfinavir, theophylline, digoxin,
ergotamine/dihydroergotamine products, benzodiazepines, and sildenafil (this will be
discontinued for the duration of the clinical trial if subject is on this
- History of elevated liver function studies or CPKs.
- Pregnancy : A urine pregnancy test will be performed at the beginning of each
treatment period and only subjects who are not pregnant will be enrolled for the
Locations and Contacts
University of Florida, Gainesville, Florida 32610, United States
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Starting date: February 2009
Last updated: December 4, 2014