Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery

Completed

• Conditions: Nutrition Disorders; Dumping Syndrome; Appetite Disorders; Delayed Gastric Emptying; Esophageal Cancer; Surgery
• Interventions: Drug: Octreotide Acetate; Diagnostic Test: Duodenal biopsy; Drug: Saline Solution; Drug: Paracetamol; Drug: Sulfasalazine

• Registration Number: NCT03734627
• Lead Sponsor: St. James's Hospital, Ireland

Brief Summary

The incidence of oesophagogastric cancer has increased by 400% since the 1970s in Ireland and the United Kingdom. In addition, refinement of perioperative management and the now widespread use of multimodal protocols for patients with locally advanced disease have significantly improved outcomes for patients with oesophagogastric cancer treatable with curative intent. Despite significant advances in chemoradiotherapy, surgical resection remains the primary curative option.

Unintentional weight loss and nutritional complications represent serious concerns for patients after radical resection, even among those who remain free from recurrent disease in the long-term. A study from the Swedish Esophageal and Cardia Cancer Registry reported a mean three year weight loss of 10.8% among disease-free patients, with 33.8% of this cohort demonstrating malnutrition at three years post-oesophagectomy.

Mechanisms contributing to weight loss for disease-free patients after upper gastrointestinal surgery are poorly understood, however an association between increasing magnitude of weight loss and the presence of increased satiety is described. Our recent studies at SJH have demonstrated four fold elevated postprandial satiety gut hormone concentrations after oesophagectomy, compared with baseline preoperative values. Postprandial gut hormone levels correlate significantly with postprandial symptoms and altered appetite at 3 months postoperatively, and with body weight loss at 2 years postoperatively. However, the mechanism leading to exaggerated postprandial gut hormone production after upper gastrointestinal surgery is poorly understood, limiting targeted therapeutic options.

In this study, we aim to characterise the role of altered nutrient transit and enteroendocrine cell function in the pathophysiology of excessive post-prandial gut hormone responses after upper gastrointestinal surgery. To do this, we will measure the gut hormone response to a standardised 400 kcal meal, as per previous studies, while concurrently assessing gastrointestinal transit time, and enteroendocrine cell morphology and function. In this way, we will determine whether the magnitude of the postprandial gut hormone response correlates with the rate of nutrient transit into the enteroendocrine L-cell rich small intestine, and whether enteroendocrine cell adaptation occurs after oesophagectomy.

Furthermore, we have previously observed that gut hormone suppression using octreotide is associated with increased ad libitum among subjects after upper gastrointestinal cancer surgery (Elliott JA et al, Annals of Surgery, 2015). The mechanism of action of octreotide may relate to SSTR-5-mediated negative feedback to the enteroendocrine L-cell, but this medication may additionally reduce enteroendocrine L-cell responses through its inhibitory effect on gastrointestinal motility - reducing the rapidity with which nutrients are delivered to the small intestine - and small intestinal nutrient sensing via inhibition of the Na+-dependent glucose transporter SGLT-18-10. Through conduction of this double-blind, randomised, placebo-controlled crossover study, we aim to establish the mechanism of action of octreotide-mediated increased food intake in patients after gastrointestinal surgery. This may inform the design of future targeted interventions for this patient group.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-01
• Study First Submitted: 2018-11-06
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-08
• Primary Completion: 2021-07-01
• Study Completion: 2021-07-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-12
• Last Update Posted: 2021-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Patient group:

1. History of upper gastrointestinal surgery at least 9 months previously

Control group:

1. Patients with suspected or confirmed non-dysplastic Barrett's oesophagus or reflux who are age, weight and gender matched to the patient cohort

Read More

Exclusion Criteria

1. Pregnancy, breastfeeding
2. Recurrent disease after surgery
3. Other active malignancy
4. Significant psychiatric disorder or cognitive decline or communication impairment limiting capacity to provide informed consent
5. Other disease or medication which may impact gut hormone physiology
6. Previous upper gastrointestinal resection
7. Certain allergies or dietary intolerances
8. Anticoagulants

Patients with contraindications to the study medications (as per www.medicines.ie) will not be automatically excluded, but will be invited to participate in an attenuated protocol where that agent is not given. It is not anticipated that this will be a frequent occurrence, however this strategy will minimise unnecessary participant exclusion.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control - Transit	Octreotide Acetate	-
Control - Transit	Saline Solution	-
Upper Gastrointestinal Surgery - Gut Function	Duodenal biopsy	-
Upper Gastrointestinal Surgery - Transit	Octreotide Acetate	-
Upper Gastrointestinal Surgery - Transit	Saline Solution	-
Upper Gastrointestinal Surgery - Transit	Sulfasalazine	-
Control - Gut Function	Duodenal biopsy	-
Upper Gastrointestinal Surgery - Transit	Paracetamol	-
Control - Transit	Paracetamol	-
Control - Transit	Sulfasalazine	-

Primary Outcome Measures

Name	Time	Method
Area under the curve for paracetamol at 30 minutes after a 400kcal mixed meal stimulus	30 minutes post meal

Secondary Outcome Measures

Name	Time	Method
Peak paracetamol level	Within 300 minutes post meal
GLP-1 area under the curve over 300 minutes after a 400kcal mixed meal stimulus	Within 300 minutes post meal
EORTC health related quality of life	At one year post surgery, on the day of assessment
Glucose area under the curve over 300 minutes after a 400kcal mixed meal stimulus	Within 300 minutes post meal
Insulin area under the curve over 300 minutes after a 400kcal mixed meal stimulus	Within 300 minutes post meal
Visual analogue scales	Within 300 minutes post meal

Trial Locations

Locations (2)

Department of Surgery, St. James's Hospital; 🇮🇪 Dublin, Ireland

Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital; 🇮🇪 Dublin, Ireland