Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Condition: Gastroparesis
MeSH terms: Gastroparesis
Intervention: Erythromycin; Azithromycin
Intervention description: 200mg/5ml elixir administered orally three times a day half an hour prior to meals.; The dose of Azithromycin given was determined based on the following study on 10 healthy subjects. In random order, each of ten healthy subjects underwent OBT studies following administration of AZI, at doses of 50mg, 100mg, and 133mg. The T½ and Tlag was then compared for the three doses by a randomized block analysis using Analysis of Variance followed by Tukey's multiple comparison. Results: The T½ for each of the respective doses of AZI (50mg, 100mg, and 133mg) was 129 ± 27, 128 ± 31, and 128 ± 16 minutes (p = 0.98). This data suggested that AZI at doses of 50mg, 100mg and 133 mg have fairly similar activity in its effects on gastric emptying in healthy subjects. Based on this analysis , we decided to use a dose of 50 mg/5 ml for administered TID prior to meals.
Intervention MeSH terms: Azithromycin; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin stearate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Gastroparesis; Gastroparesis Treatment; Gastric Emptying; Prokinetic Agents; Macrolides; Erythromycin; Azithromycin; Erythromycin Cardiac Side-effects; Erythromycin drug interactions; AZI

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  presenting to gastroenterology motility specialty clinics at the University of Florida
             (UF), who meet the clinical and radiologic diagnostic criteria for diagnosis of GP

        Exclusion Criteria:

          -  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 medication).

          -  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
             study.