Clinical trial NCT01323582: Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Official title: Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gastroparesis
Keywords: Gastroparesis
Gastroparesis Treatment
Gastric Emptying
Prokinetic Agents
Macrolides
Erythromycin
Azithromycin
Erythromycin Cardiac Side-effects
Erythromycin drug interactions
AZI
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Metabolic Solutions Inc.
First posted: 2011-03-25
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: 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.
timeFrame: Weeks 4 and 11 (end of periods)
measure: Gastroparesis Cardinal Symptom Index (GCSI) Score
timeFrame: Weeks 4 and 11 (end of periods)
Secondary outcomes:
measure: NDI Score
timeFrame: Weeks 4 and 11 (end of periods)
measure: TLAG (Time From Ingestion of Meal to Start of Gastric Emptying)
timeFrame: Weeks 4 and 11 (end of periods)
measure: Change in Time to 50% Gastric Emptying: Post Test Less Baseline Pooled Over Orderings
timeFrame: Baseline and end of treatment period
measure: Change in Time to 50% Emptying: Post Test Less Baseline Pooled Over Orderings
timeFrame: at baseline before initiation of the treatment and after completion of each treatment period.
measure: Gastroparesis Cardinal Symptom Index (GCSI) Score Change From Baseline to Post Treatment
timeFrame: Baseline and end of treatment period
measure: Does GCSI Score Improve (Lower) on Treatment, Pooling the AZ Patients Over Their Treatment Periods? Endpoint is Difference in Post-test Less Baseline
timeFrame: Baseline and end of treatment period
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Baharak Moshiree, MD
role: PRINCIPAL_INVESTIGATOR
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