Courcoulas Anita P, Stefater Margaret A, Shirley Eleanor, Gourash William F, Stylopoulos Nicholas
University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
Endocrinology, Boston Children's Hospital, Boston, MA, United States.
JMIR Res Protoc. 2019 Jan 24;8(1):e12459. doi: 10.2196/12459.
Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the best treatment for severe obesity and its complications including type 2 diabetes mellitus (T2DM). Understanding the mechanisms responsible for the beneficial metabolic effects will help to engineer ways to improve the procedure or produce these effects without surgery.
The aim is to present data on recruitment and feasibility of a translational study designed to collect intestinal samples before and after bariatric surgery. The goal of biobanking is to allow future studies to test the hypothesis that the mechanism of action of RYGB involves specific changes in the postsurgical short- and long-term metabolism and morphology of the jejunum (Roux limb). Specifically, to test whether the intestine enhances its metabolism and activity after RYGB and increases its fuel utilization, we designed a prospective, longitudinal study, which involved the recruitment of candidates for RYGB with and without T2DM. We describe the tissue bank that we have generated, and our experience, hoping to further facilitate the performance of longitudinal mechanistic studies in human patients undergoing bariatric surgery and especially those involving post-RYGB intestinal biology.
We conducted a trial to characterize the effects of RYGB on intestinal metabolism. Intestinal tissue samples were collected from the jejunum at surgery, 1, 6, and 12 months postoperatively for the analysis of intestinal gene expression and metabolomic and morphologic changes. The target number of patients who completed at least the 6-month follow-up was 26, and we included a 20% attrition rate, increasing the total number to 32.
To enroll 26 patients, we had to approach 79 potential participants. A total of 37 agreed to participate and started the study; 33, 30, and 26 active participants completed their 1-month, 6-month, and 12-month studies, respectively. Three participants withdrew, and 30 participants are still active. Altruism and interest in research were the most common reasons for participation. Important factors for feasibility and successful retention included (1) large volume case flow, (2) inclusion and exclusion criteria broad enough to capture a large segment of the patient population but narrow enough to ensure the completion of study aims and protection of safety concerns, (3) accurate assessment of willingness and motivation to participate in a study, (4) seamless integration of the recruitment process into normal clinical flow, (5) financial reimbursement and nonfinancial rewards and gestures of appreciation, and (6) nonburdensome follow-up visits and measures and reasonable time allotted.
Human translational studies of the intestinal mechanisms of metabolic and weight changes after bariatric surgery are important and feasible. A tissue bank with unique samples has been established that could be used by investigators in many research fields, further enabling mechanistic studies on the effects of bariatric surgery.
ClinicalTrials.gov NCT02710370; https://clinicaltrials.gov/ct2/show/NCT02710370 (Archived by WebCite at http://www.webcitation.org/75HrQT8Dl).
减重手术，尤其是 Roux-en-Y 胃旁路术（RYGB），是治疗重度肥胖及其并发症（包括 2 型糖尿病（T2DM））的最佳方法。了解产生有益代谢效应的机制将有助于设计出改进该手术的方法，或在不进行手术的情况下产生这些效应。
本研究旨在展示一项转化研究的招募情况和可行性数据，该研究旨在收集减重手术前后的肠道样本。生物样本库的目标是使未来的研究能够检验以下假设：RYGB 的作用机制涉及术后空肠（Roux 袢）短期和长期代谢及形态的特定变化。具体而言，为了检验 RYGB 术后肠道是否增强了其代谢和活性并增加了燃料利用，我们设计了一项前瞻性纵向研究，该研究招募了患有和未患有 T2DM 的 RYGB 候选患者。我们描述了已建立的组织库以及我们的经验，希望能进一步推动对接受减重手术的人类患者，尤其是涉及 RYGB 术后肠道生物学的纵向机制研究。
我们进行了一项试验，以表征 RYGB 对肠道代谢的影响。在手术时、术后 1 个月、6 个月和 12 个月从空肠收集肠道组织样本，用于分析肠道基因表达、代谢组学和形态学变化。完成至少 6 个月随访的目标患者数量为 26 例，我们设定了 20%的损耗率，将总数增加到 32 例。
为招募 26 名患者，我们不得不联系 79 名潜在参与者。共有 37 人同意参与并开始研究；分别有 33 名、30 名和 26 名活跃参与者完成了他们的 1 个月、6 个月和 12 个月研究。3 名参与者退出，30 名参与者仍在参与。利他主义和对研究的兴趣是参与的最常见原因。可行性和成功保留的重要因素包括：（1）大量病例流；（2）纳入和排除标准足够宽泛以涵盖大部分患者群体，但又足够狭窄以确保完成研究目标并保障安全问题；（3）准确评估参与研究的意愿和动机；（4）将招募过程无缝整合到正常临床流程中；（5）经济补偿以及非经济奖励和感谢表示；（6）随访访问和措施不繁重且分配合理时间。
关于减重手术后肠道代谢和体重变化机制的人体转化研究是重要且可行的。已建立了一个拥有独特样本的组织库，可供许多研究领域的研究人员使用，进一步推动了对减重手术效果的机制研究。
ClinicalTrials.gov NCT02710370；https://clinicaltrials.gov/ct2/show/NCT02710370（由 WebCite 存档于 http://www.webcitation.org/75HrQT8Dl）
