Progression of Gastroesophageal Reflux Disease and Barrett's Esophagus and the Creation of a Barrett's Registry

Официальное название

A Prospective Study To Define The Role Of Various Factors In Development And Progression Of Gastroesophageal Reflux Disease (GERD) And Barrett's Esophagus And The Creation Of A Registry.

Обзор

The purpose of this study is to determine or evaluate the risk factors such as smoking, family history etc. that cause esophageal cancer and to determine the genetic changes that lead to esophageal cancer. The investigators hypothesis is that systematic collection of data on the natural history of GERD and BE patients and risk factors for development of BE in patients with chronic GERD and progression of BE to dysplasia and adenocarcinoma will provide useful information to develop a decision model for risk stratification and risk reduction strategies in these patients. As of March 17, 2011, 585 patients have consented at the Kansas City VA Medical Center.

Подробное описание

Symptoms of gastroesophageal reflux are common. It affects at least 40% of the adult American population and 40 million American adults experience reflux symptoms on a regular basis. Gastroesophageal reflux disease (GERD) typically affects Caucasians and older males. It is a significant risk factor for development of Barrett's esophagus (BE) and esophageal adenocarcinoma. Approximately 10-15% of patients with chronic GERD are diagnosed with BE, a premalignant lesion for esophageal adenocarcinoma. Adenocarcinoma of the esophagus continues to be the most rapidly increasing incidence cancer in the United States. Based on studies evaluating screening/surveillance strategies, it is clear that it is imperative to identify risk factors that would target those patients with gastroesophageal reflux disease (GERD) and BE that may benefit from screening and surveillance strategies, yet also be practical and cost-effective. A better understanding of the events surrounding the development of BE in patients with chronic GERD, development of dysplastic changes in patients with BE and progression of BE to adenocarcinoma may ultimately help in identifying those patients at increased risk. Thus, our hypothesis is that systematic collection of data on the natural history of GERD and BE patients and risk factors for development of BE in patients with chronic GERD and progression of BE to dysplasia and adenocarcinoma will provide useful information to develop a decision model for risk stratification and risk reduction strategies in these patients. This model will be a useful tool leading to a reduction in overall health care costs.

The study will be conducted at the Kansas City Department of Veterans Affairs Medical Center. This is a prospective cohort study designed to analyze the epidemiologic and genetic factors relevant to development of BE in patients with GERD and its subsequent progression to dysplasia and adenocarcinoma. 1) The consenting patients as well as controls (2:1 ratio) will be asked to fill validated questionnaire on severity of GERD and food frequency. Data regarding medications, family history and social history will also be collected. 2) The endoscopy and pathology reports will be browsed for length of Barrett's esophagus confirmed by histology, length of hiatal hernia and presence of helicobacter pylori. 3) Serum samples from participating patients will be collected and frozen for measurements of insulin, glucose, lipid panel, CRP and adiponectin levels. Biopsies obtained from esophagus during endoscopy and blood samples would be frozen for future biomarker and cDNA microarray studies and histochemistry.

Approximately10-20% of the adult population has GERD and 0.5 to 2% of the adult population (1-4 million individuals) is estimated to have BE and it is a known precursor to esophageal adenocarcinoma. However, we are not yet able to reliably identify those individuals with GERD that are at risk for developing BE and with BE who are at high risk for progressing to esophageal adenocarcinoma. The identification of risk factors as the ultimate goal of this study will enable us to better identify the high-risk patients and provide early intervention and therapeutic strategies in a cost-effective manner.

Первичные конечные точки

• The goal of this study is to follow GERD and BE pts prospectively for development of dysplasia and adenocarcinoma, to identify factors responsible for progression of GERD to BE to dysplasia and adenocarcinoma. [Срок оценки: 5 plus years]

Вторичные конечные точки (1)

• The secondary goal is to create a tissue and serum repository for future biomarker studies. [Срок оценки: 5 plus years]

Критерии участия

All patients must be eligible for care that the Kansas City VA Hospital where this study was approved for enrollment.

Критерии включения

• Kansas City VA Patients with confirmed BE with and without dysplasia and patients with reflux disease (patients/cases); patients with other indicators for endoscopy such as anemia, weight loss, diarrhea, but without GERD and PE (controls).

Критерии исключения

• Patients with uncontrolled significant comorbidities such as cardiovascular, pulmonary, renal, hepatic or metabolic diseases.
• Presence of anticoagulation that would increase risk from biopsies
• Patients unable to provide history
• Patients with dyspepsia

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• Department of Veterans Affairs Medical Center — Kansas City

Публикации

• Sampliner RE; Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol. 2002 Aug;97(8):1888-95. doi: 10.1111/j.1572-0241.2002.05910.x. No abstract available. PMID 12190150
• Haggitt RC. Barrett's esophagus, dysplasia, and adenocarcinoma. Hum Pathol. 1994 Oct;25(10):982-93. doi: 10.1016/0046-8177(94)90057-4. PMID 7927321
• Reid BJ. Barrett's esophagus and esophageal adenocarcinoma. Gastroenterol Clin North Am. 1991 Dec;20(4):817-34. PMID 1787015
• van Sandick JW, van Lanschot JJ, Kuiken BW, Tytgat GN, Offerhaus GJ, Obertop H. Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological stage and clinical outcome of Barrett's carcinoma. Gut. 1998 Aug;43(2):216-22. doi: 10.1136/gut.43.2.216. PMID 10189847
• Gudlaugsdottir S, van Blankenstein M, Dees J, Wilson JH. A majority of patients with Barrett's oesophagus are unlikely to benefit from endoscopic cancer surveillance. Eur J Gastroenterol Hepatol. 2001 Jun;13(6):639-45. doi: 10.1097/00042737-200106000-00005. PMID 11434588
• van der Burgh A, Dees J, Hop WC, van Blankenstein M. Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus. Gut. 1996 Jul;39(1):5-8. doi: 10.1136/gut.39.1.5. PMID 8881798
• O'Connor JB, Falk GW, Richter JE. The incidence of adenocarcinoma and dysplasia in Barrett's esophagus: report on the Cleveland Clinic Barrett's Esophagus Registry. Am J Gastroenterol. 1999 Aug;94(8):2037-42. doi: 10.1111/j.1572-0241.1999.01275.x. PMID 10445525
• Wong A, Fitzgerald RC. Epidemiologic risk factors for Barrett's esophagus and associated adenocarcinoma. Clin Gastroenterol Hepatol. 2005 Jan;3(1):1-10. doi: 10.1016/s1542-3565(04)00602-0. PMID 15645398

Идентификаторы

NCT: NCT00574327 · PS0035

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗