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

Information source: University of Florida
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Gastroparesis

Intervention: Erythromycin (Drug); Azithromycin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Florida

Official(s) and/or principal investigator(s):
Baharak Moshiree, MD, MS, Principal Investigator, Affiliation: University of Florida

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.

Clinical Details

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

Primary outcome: Assessment of gastric emptying with a standardized breath test

Secondary outcome:

Gastroparesis Cardinal Symptom Index (GCSI) Score

symptom severity score (SSS)

Patient Diary on Gastrointestinal Symptoms

The SF-36 questionnaire

Nepean Dyspepsia Index (NDI)

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

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Locations and Contacts

University of Florida, Gainesville, Florida, United States; Recruiting
Lasheaka V McClellan, Phone: 352-392-6293, Email: Lasheaka.McClellan@medicine.ufl.edu
Cheryl Curington, BS, Phone: (352)392-6293, Email: Cheryl.Curington@medicine.ufl.edu
Baharak Moshiree, MD, MS, Principal Investigator
Additional Information

Related publications:

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Talley NJ, Locke GR 3rd, Lahr BD, Zinsmeister AR, Tougas G, Ligozio G, Rojavin MA, Tack J. Functional dyspepsia, delayed gastric emptying, and impaired quality of life. Gut. 2006 Jul;55(7):933-9. Epub 2005 Dec 1.

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Nyrén O, Adami HO, Bates S, Bergström R, Gustavsson S, Lööf L, Sjödén PO. Self-rating of pain in nonulcer dyspepsia. A methodological study comparing a new fixed-point scale and the visual analogue scale. J Clin Gastroenterol. 1987 Aug;9(4):408-14.

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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.

Talley NJ, Haque M, Wyeth JW, Stace NH, Tytgat GN, Stanghellini V, Holtmann G, Verlinden M, Jones M. Development of a new dyspepsia impact scale: the Nepean Dyspepsia Index. Aliment Pharmacol Ther. 1999 Feb;13(2):225-35.

Starting date: February 2009
Last updated: September 16, 2011

Page last updated: December 08, 2011

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