Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis (AZI)

This study has been terminated.
(Original investigator left this institution, replacement investigator retired and study closed with the IRB.)
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01323582
First received: March 24, 2011
Last updated: July 16, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Gastroparesis
Drug: Erythromycin
Drug: Azithromycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Assessment of gastric emptying with a standardized breath test [ Time Frame: a baseline prior to initiation of treatment and after each 4-week treatment period ] [ Designated as safety issue: No ]
    patients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed


Secondary Outcome Measures:
  • Gastroparesis Cardinal Symptom Index (GCSI) Score [ Time Frame: At baseline prior to initiation of treatment and at 2 and 4 weeks after each treatment period ] [ Designated as safety issue: No ]
    This scoring is based on Likert scale.

  • symptom severity score (SSS) [ Time Frame: At baseline prior to initiation of treatment and at 2 and 4 weeks after each treatment period ] [ Designated as safety issue: No ]
    GI symptoms are scored for their severity and analyzed.

  • Patient Diary on Gastrointestinal Symptoms [ Time Frame: at baseline and every week after that ] [ Designated as safety issue: No ]
    Patients will self report their GI symptoms in a patient diary. This diary will be reviewed at each clinic visit.

  • The SF-36 questionnaire [ Time Frame: at baseline before initiation of the treatment and after completion of each treatment period. ] [ Designated as safety issue: No ]
    It is a generic health status questionnaire.

  • Nepean Dyspepsia Index (NDI) [ Time Frame: at baseline before initiation of the treatment and after completion of each treatment period. ] [ Designated as safety issue: No ]
    A measure of symptom status and quality of life in functional dyspepsia.


Enrollment: 37
Study Start Date: February 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: erythromycin
200mg/5ml elixir administered orally three times a day half an hour prior to meals.
Drug: Erythromycin
200mg/5ml elixir administered orally three times a day half an hour prior to meals.
Other Name: Erythromycin ethylsuccinate
Experimental: Azithromycin
The dose of Azithromycin given will be determined based on our dose response curve however the appearance of the medication and administration period will be identical to that of Erythromycin, i.e. 5ml elixir administered orally three times a day half an hour prior to meals. The total daily dosage of Azithromycin however will not exceed 400mg.
Drug: Azithromycin
The dose of Azithromycin given will be determined based on our dose response curve however the appearance of the medication and administration period will be identical to that of Erythromycin, i.e. 5ml elixir administered orally three times a day half an hour prior to meals. The total daily dosage of Azithromycin however will not exceed 400mg.
Other Name: azithromycin

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01323582

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Phillip P Toskes, MD University of Florida
  More Information

Publications:
Lee JS, Camilleri M, Zinsmeister A, et al. Accurate simple measurement of gastric emptying by 13C octanoic acid breath test (OBT) in diabetes. Gastroenterology 1999; 116: G4207.

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01323582     History of Changes
Other Study ID Numbers: 645-2008
Study First Received: March 24, 2011
Last Updated: July 16, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Florida:
Gastroparesis
Gastroparesis Treatment
Gastric Emptying
Prokinetic Agents
Macrolides
Erythromycin
Azithromycin
Erythromycin Cardiac Side-effects
Erythromycin drug interactions
AZI

Additional relevant MeSH terms:
Gastroparesis
Digestive System Diseases
Gastrointestinal Diseases
Neurologic Manifestations
Paralysis
Signs and Symptoms
Stomach Diseases
Erythromycin
Erythromycin Estolate
Erythromycin Ethylsuccinate
Erythromycin stearate
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014