Open Label Transdermal Granisetron to Relieve Chronic Nausea and Emesis and to Reduce Medical Utilization in Patients With Gastroparesis
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Number of participants with improvement in chronic nausea and emesis.
研究概览
简要总结
To determine the efficacy of open -label transdermal patch on chronic nausea and emesis in patients with gastroparesis
详细描述
Gastroparesis is a chronic syndrome associated with a delay in stomach emptying. The clinical presentation of gastroparesis is very heterogeneous but can generally categorized into emesis-predominant, regurgitation-predominant and dyspeptic-predominant gastroparesis.
The underlying cause of nausea is very difficult to identify, and physician is often treat nausea symptomatically with anti-nausea and anti-emetic medications.4, 5 Phenothiazine's such as prochlorperazine (Compazine®), promethazine (Phenergan®), and trimethobenzamide (Tigan®) have significant side effects and the potential of withdraw symptoms when these medications are stopped. Serotonin (5- HT3) antagonists have central emetic effects and have been utilized in acute chemotherapy-induced nausea and vomiting. Ondansetron, granisetron, palonosetron, and dolasetron are currently available as 5- HT3 antagonists for nausea and emesis. Oral dissolving and oral tablet formulation is suboptimal in outpatients with frequent emesis. Transdermal formulation may be optimal for patients with prolong nausea and vomiting, but data for chronic symptoms associated with gastroparesis is very limited.
An open-label, uncontrolled treatment pilot study with 2-week cycles of granisetron transdermal patch for 24 weeks in patients with chronic nausea and vomiting associated with gastroparesis
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented delayed gastric emptying by 4-hr gastric scintigraphy using the standard protocol within 12 months.6
- •Symptoms of gastroparesis for >3 months
- •No upper gastrointestinal obstruction by upper endoscopy, barium radiograph, or CT scan.
- •Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V) subscale score of >2.0 during a 2-week run-in period.
排除标准
- •Baseline ECG with QTc >450ms in men or >470ms in women
- •Prolong QT syndrome
- •History of Torsade's de pointes, ventricular tachycardia, cardiomyopathy or implanted cardiac defibrillator
- •Use of cardiovascular antiarrhythmic medications
- •Strong CYP1A1 and CYP3A4 inhibitors that will inhibit metabolism of 5-HT3 antagonists
- •CYP1A1 Inhibitors: pifithrin, ethinyl estradiol, fluvoxamine (Luvox®), mexiletine, miconazole, oltipraz , perazine, rofecoxib, aminobenzotriazole, isoniazid, lidocaine, zileuton (Zyflo®)
- •CYP3A strong inhibitors: boceprevir, cobicistat (Tybost®), conivaptan (Vaprisol®), danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole (Onmel®, Sporanox®), ketoconazole, lopinavir and ritonavir (Kaletra®), paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole (Noxafil®), ritonavir (Norvir®), saquinavir and ritonavir), tipranavir and ritonavir, troleandomycin, voriconazole (Vfend®), clarithromycin (Biaxin®), diltiazem (Cardizem®, Cartia®, Dilacor®, Dilt-CD®, Diltia XT®, Taztia XT®, Tiazac®), idelalisib (Zydelig®), nefazodone (Serzone®), nelfinavir (Viracept®)
- •Serotonergic drugs that may increase the risk of serotonin syndrome
- •Selective serotonin reuptake inhibitors (SSRIs)
- •Selective norepinephrine reuptake inhibitors (SNRIs)
- •Others: monoamine oxidase inhibitors: selegiline (Emsam®), isocarboxazid (Marplan®), pheneizine (Nardil®), tranylcypromine (Parnate®), mirtazapine (Remeron®), fentanyl (Sublimaze®), lithium (Eskalith®, Lithobid®), tramadol (ConZip®, Rybix®, Ryzolt®, Ultram®), intravenous methylene blue
- •Any comorbid condition that may prohibit enrollment
- •Other causes of nausea identified by the investigators other than gastroparesis
- •Any contraindications for 5HT3 receptor antagonists
- •Non-ambulatory patients: bed-ridden, nursing home resident, etc.
- •Unable to give own informed consent
研究组 & 干预措施
Patch arm
Transdermal Granisetron patch to be given for application for 24 weeks with 2 weeks on and one week off pattern for a total of 24 weeks
干预措施: Granisetron (Drug)
结局指标
主要结局
Number of participants with improvement in chronic nausea and emesis.
时间窗: 24 weeks
Incidence of participants who benefitted from the use of the patch at the end of 2 weeks, 8 weeks, 16 weeks and 24 weeks as assessed by the Gastroparesis Cardinal Symptom Index Nausea-Vomiting (GCSI-N/V). Mean subscale scores will compared for improvement every 6 weeks.
次要结局
- Number of participants with reduced medical utilization for gastroparesis.(24 weeks)
研究者
John M. Wo
Professor of Gastroenterology
Indiana University