Clinical trial NCT02381249: The Effect of Satiety Gut Hormone Modulation on Appetitive Drive After Upper Gastrointestinal Surgery
Official title: The Effect of Satiety Gut Hormone Modulation on Appetitive Drive After Upper Gastrointestinal Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Neoplasms
Stomach Neoplasms
Weight Loss
Malnutrition
Pancreatic Neoplasms
Duodenal Neoplasms
Keywords: Esophagectomy
Gastrectomy
Octreotide
Somatostatin
Appetite
Hunger
Glucagon-Like Peptide 1
Peptide YY
Reinforcement
Reward
Psychological Phenomena and Processes
Gastrointestinal Agents
Nutritional Status
Pancreaticoduodenectomy
Whipple Procedure
Lead sponsor: St. James's Hospital, Ireland
Sponsor class: OTHER
Collaborators: name: University College Dublin
name: University of Dublin, Trinity College
name: Göteborg University
First posted: 2015-03-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Improvements to treatment strategies for patients with cancers of the upper gastrointestinal tract have produced a large population of people who remain free from cancer recurrence in the long term following treatment.

Surgery is the cornerstone of treatment for patients with these cancers, but while surgical removal of the tumour may offer the best chance of cure, these are major operations associated with specific long term complications. Weight loss and poor nutrition are common problems among patients who attain long-term cancer remission and cure after surgery. The mechanisms underlying these problems are not well understood and therefore treatment options are limited.

Our research has demonstrated increased levels of chemical messengers (gut hormones) released from the gastrointestinal tract after meals in patients who have previously undergone this type of surgery. These chemical messengers play a role in controlling appetite and interest in food, and increased levels after surgery may reduce interest in eating. Understanding the role of gut hormones in the control of appetite may allow us to use certain medications to block gut hormones and hence increase appetite, allowing patients to eat more and regain weight, preventing nutritional problems after surgery.

In this study, the investigators aim to determine whether exaggerated gut hormone secretion causes reduced appetite and interest in food after surgery. The information gained from this study may help us to develop treatments for patients with weight loss and nutritional problems after surgery.


Eligibility criteria: Inclusion criteria:

1. Surgical procedure: Two-stage, three-stage or transhiatal esophagectomy with gastric conduit reconstruction and pyloroplasty, total gastrectomy with Roux-en-Y reconstruction, pancreaticoduodenectomy, or matched healthy unoperated control subjects
2. Disease-free at least one year post-resection

Exclusion criteria:

1. Pregnancy, breastfeeding
2. Significant and persistent chemoradiotherapy and/or surgical complication
3. Other previous upper gastrointestinal surgery
4. Unwell or unable to eat
5. Other disease or medications which may affect satiety gut hormone responses
6. Active and significant psychiatric illness including substance misuse
7. Cognitive or communication issues or any factors affecting capacity to consent to participation
8. History of significant food allergy, certain dietary restrictions
9. Confirmed or suspected residual or recurrent disease after surgery, second primary malignancy
10. Requiring adjuvant chemotherapy
11. Contraindication to octreotide administration
12. History of eating disorder

Primary outcomes:
measure: Progressive ratio task breakpoint for a sweet-fat reward
timeFrame: 3 hours
Secondary outcomes:
measure: Number of rewards consumed
timeFrame: 3 hours
measure: Subjective symptom score
timeFrame: 3 hours
Other outcomes:
measure: Sigstad score
timeFrame: 3 hours
Locations:
city: Dublin
country: Ireland
facility: Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital
city: Gothenburg
country: Sweden
facility: Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg
Study officials:
affiliation: Department of Surgery, St. James's Hospital
name: John V Reynolds, MCh, FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miras AD, Jackson RN, Jackson SN, Goldstone AP, Olbers T, Hackenberg T, Spector AC, le Roux CW. Gastric bypass surgery for obesity decreases the reward value of a sweet-fat stimulus as assessed in a progressive ratio task. Am J Clin Nutr. 2012 Sep;96(3):467-73. doi: 10.3945/ajcn.112.036921. Epub 2012 Jul 25.
citation: HODOS W. Progressive ratio as a measure of reward strength. Science. 1961 Sep 29;134(3483):943-4. doi: 10.1126/science.134.3483.943.
citation: Miholic J, Orskov C, Holst JJ, Kotzerke J, Pichlmayr R. Postprandial release of glucagon-like peptide-1, pancreatic glucagon, and insulin after esophageal resection. Digestion. 1993;54(2):73-8. doi: 10.1159/000201016.
citation: Haverkort EB, Binnekade JM, Busch OR, van Berge Henegouwen MI, de Haan RJ, Gouma DJ. Presence and persistence of nutrition-related symptoms during the first year following esophagectomy with gastric tube reconstruction in clinically disease-free patients. World J Surg. 2010 Dec;34(12):2844-52. doi: 10.1007/s00268-010-0786-8.
citation: Koizumi M, Hosoya Y, Dezaki K, Yada T, Hosoda H, Kangawa K, Nagai H, Lefor AT, Sata N, Yasuda Y. Postoperative weight loss does not resolve after esophagectomy despite normal serum ghrelin levels. Ann Thorac Surg. 2011 Apr;91(4):1032-7. doi: 10.1016/j.athoracsur.2010.11.072.
citation: le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006 Jan;243(1):108-14. doi: 10.1097/01.sla.0000183349.16877.84.
citation: Elliott JA, Docherty NG, Haag J, Eckhardt HG, Ravi N, Reynolds JV, le Roux CW. Attenuation of satiety gut hormones increases appetitive behavior after curative esophagectomy for esophageal cancer. Am J Clin Nutr. 2019 Feb 1;109(2):335-344. doi: 10.1093/ajcn/nqy324.