Comparison of Two Macrolides, Azithromycin and Erythromycin, for Symptomatic Treatment of Gastroparesis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •presenting to gastroenterology motility specialty clinics at the University of Florida (UF), who meet the clinical and radiologic diagnostic criteria for diagnosis of GP
排除标准
- •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.
研究组 & 干预措施
erythromycin
200mg/5ml elixir administered orally three times a day half an hour prior to meals.
干预措施: Erythromycin (Drug)
Azithromycin
The dose of Azithromycin was determined based on our dose response curve obtained on 10 healthy subjects who were given three different doses of Azithromycin, 50 mg, 100 mg and 133 mg and underwent breath testing to determine the gastric emptying half-time. These doses were determined based on a maximum safe dosage per day of Azithromycin of 400 mg given the medication would then be administered three times daily before meals. The appearance of the medication (azithromycin) and administration period was then 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 was determined after obtaining the dose- response analysis.
干预措施: Azithromycin (Drug)
结局指标
主要结局
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.
时间窗: Weeks 4 and 11 (end of periods)
Patients will be given a standardized meal enriched with a labeled material and the breath samples are then collected and analyzed. The estimated time to empty 50% (t 1/2) of the accumulated contents is recorded. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
Gastroparesis Cardinal Symptom Index (GCSI) Score
时间窗: Weeks 4 and 11 (end of periods)
This is a Validated instrument for measuring symptom severity in patients with gastroparesis. This scoring is based on a Likert Scale from (0-5) with zero being no symptoms and five being very severe symptoms on 9 subscales, making the overall score range from 0-45. The higher the score, the more severe patient's symptoms. Reference for GCSI: Revicki DA, REntz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptoms severity measure: the Gastroparesis Cardinal Symptom Index. Ailment Pharm Ther 2003; 18: 141:50. Because the difference is RX-B -RX A in one group and RX A -RX B in the other, the difference between these two estimates twice the effect size. Hence the Half is applied, as is standard in the two sample method for crossover studies.
次要结局
- NDI Score(Weeks 4 and 11 (end of periods))
- Change in Time to 50% Gastric Emptying: Post Test Less Baseline Pooled Over Orderings(Baseline and end of treatment period)
- TLAG (Time From Ingestion of Meal to Start of Gastric Emptying)(Weeks 4 and 11 (end of periods))
- Change in Time to 50% Emptying: Post Test Less Baseline Pooled Over Orderings(at baseline before initiation of the treatment and after completion of each treatment period.)
- Gastroparesis Cardinal Symptom Index (GCSI) Score Change From Baseline to Post Treatment(Baseline and end of treatment period)
- Does GCSI Score Improve (Lower) on Treatment, Pooling the AZ Patients Over Their Treatment Periods? Endpoint is Difference in Post-test Less Baseline(Baseline and end of treatment period)