Food Intake and Gut Hormones in Patients Who Have Undergone Upper Gastrointestinal Surgery for Cancer

NCT02385617 | Completed

• 2 other identifiers: CRFSJ 0026REC 2011/27/01
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

Improvements to treatment strategies for patients upper gastrointestinal cancers have produced an increasing population of people who remain free from disease recurrence in the long term. Weight loss and nutritional problems are common among patients who attain long-term remission and cure after surgery for upper gastrointestinal cancers. However, the mechanisms underlying these problems are not well understood. In this study the investigators aim to determine whether reduced food intake after upper gastrointestinal surgery is caused by early satiety related to exaggerated post-prandial gut hormone responses. This is a randomized, double-blind, placebo controlled, crossover study of the effect of 100μg octreotide SC on ad libitum food intake in patients free from complications or recurrence at least one year post-oesophagectomy, gastrectomy or pancreaticoduodenectomy. A comparator group of age, weight and gender matched subjects will be studied concurrently, and caloric intake and subjective symptom scores after administration of octreotide versus placebo among surgical and comparator subjects will be assessed.

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Weight Loss; Malnutrition

Keywords

Glucagon-Like Peptide 1; Peptide YY; Ghrelin; Satiety Response; Appetite; Hunger; Somatostatin; Octreotide; Anastomosis, Roux-en-Y; Digestive System Surgical Procedures; Pharmacologic Actions; Physiological Effects of Drugs; Endocrine System Diseases; Enteroendocrine Cells; Gastrointestinal Agents

Outcome Measures

Primary Outcomes (1)

• Ad libitum calorie intake

  Total kcals consumed

  1 hour

Secondary Outcomes (2)

• Post-prandial satiety gut hormone response

  2 hours

• Subjective symptom scores

  3 hours

Study Arms (4)

Esophagectomy

EXPERIMENTAL

Double blind single dose placebo-octreotide crossover

Drug: Octreotide; Drug: Placebo

Total gastrectomy

EXPERIMENTAL

Double blind single dose placebo-octreotide crossover

Drug: Octreotide; Drug: Placebo

Control - no surgery

ACTIVE COMPARATOR

Double blind single dose placebo-octreotide crossover

Drug: Octreotide; Drug: Placebo

Pancreaticoduodenectomy

EXPERIMENTAL

Double blind single dose placebo-octreotide crossover

Drug: Octreotide; Drug: Placebo

Interventions

Octreotide DRUG

Octreotide 100mcg (1mL) single dose, subcutaneously, into the lower abdomen, 50 minutes prior to eating

Also known as: Sandostatin

Control - no surgery; Esophagectomy; Pancreaticoduodenectomy; Total gastrectomy

Placebo DRUG

0.9% saline (1mL) single dose, subcutaneously, into the lower abdomen, 50 minutes prior to eating

Control - no surgery; Esophagectomy; Pancreaticoduodenectomy; Total gastrectomy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Surgical procedure: Two-stage, three-stage or transhiatal oesophagectomy with gastric conduit reconstruction and pyloroplasty, total gastrectomy with Roux-en-Y reconstruction, pancreaticodueodenectomy, or matched unoperated healthy controls
• At least one year in remission post-resection (surgical groups)

You may not qualify if:

• Pregnancy, breastfeeding
• Significant and persistent chemoradiotherapy and/or surgical complication
• Other previous upper gastrointestinal surgery
• Significant dysphagia or odynophagia, unable to eat
• Other disease or medications which may affect satiety gut hormone responses
• Active and significant psychiatric illness including substance misuse
• Cognitive or communication issues or any factors affecting capacity to consent to participation
• History of significant food allergy, certain dietary restrictions
• Confirmed or suspected residual or recurrent disease after surgery, second primary malignancy
• Other reconstruction (eg colonic or jejunal interposition)
• Any contraindication to octreotide administration

Sponsors & Collaborators

• St. James's Hospital, Ireland: lead
• University College Dublin: collaborator
• University of Dublin, Trinity College: collaborator
• Göteborg University: collaborator

Study Sites (2)

Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital

Dublin, D8, Ireland

Location

Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg

Gothenburg, Sweden

Location

Related Publications (11)

• le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, Lonroth H, Fandriks L, Ghatei MA, Bloom SR, Olbers T. Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg. 2007 Nov;246(5):780-5. doi: 10.1097/SLA.0b013e3180caa3e3.

  PMID: 17968169 BACKGROUND

• Martin L, Lagergren J, Lindblad M, Rouvelas I, Lagergren P. Malnutrition after oesophageal cancer surgery in Sweden. Br J Surg. 2007 Dec;94(12):1496-500. doi: 10.1002/bjs.5881.

  PMID: 17668914 BACKGROUND

• Haverkort EB, Binnekade JM, de Haan RJ, Busch OR, van Berge Henegouwen MI, Gouma DJ. Suboptimal intake of nutrients after esophagectomy with gastric tube reconstruction. J Acad Nutr Diet. 2012 Jul;112(7):1080-7. doi: 10.1016/j.jand.2012.03.032.

  PMID: 22889637 BACKGROUND

• Donohoe CL, McGillycuddy E, Reynolds JV. Long-term health-related quality of life for disease-free esophageal cancer patients. World J Surg. 2011 Aug;35(8):1853-60. doi: 10.1007/s00268-011-1123-6.

  PMID: 21553202 BACKGROUND

• Reynolds JV, McLaughlin R, Moore J, Rowley S, Ravi N, Byrne PJ. Prospective evaluation of quality of life in patients with localized oesophageal cancer treated by multimodality therapy or surgery alone. Br J Surg. 2006 Sep;93(9):1084-90. doi: 10.1002/bjs.5373.

  PMID: 16779881 BACKGROUND

• 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.

  PMID: 8319842 BACKGROUND

• Miras AD, le Roux CW. Mechanisms underlying weight loss after bariatric surgery. Nat Rev Gastroenterol Hepatol. 2013 Oct;10(10):575-84. doi: 10.1038/nrgastro.2013.119. Epub 2013 Jul 9.

  PMID: 23835488 BACKGROUND

• 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.

  PMID: 21440118 BACKGROUND

• Doki Y, Takachi K, Ishikawa O, Miyashiro I, Sasaki Y, Ohigashi H, Nakajima H, Hosoda H, Kangawa K, Sasakuma F, Motoori M, Imaoka S. Ghrelin reduction after esophageal substitution and its correlation to postoperative body weight loss in esophageal cancer patients. Surgery. 2006 Jun;139(6):797-805. doi: 10.1016/j.surg.2005.11.015.

  PMID: 16782437 BACKGROUND

• Miyazaki T, Tanaka N, Hirai H, Yokobori T, Sano A, Sakai M, Inose T, Sohda M, Nakajima M, Fukuchi M, Kato H, Kuwano H. Ghrelin level and body weight loss after esophagectomy for esophageal cancer. J Surg Res. 2012 Jul;176(1):74-8. doi: 10.1016/j.jss.2011.09.016. Epub 2011 Oct 3.

  PMID: 22137988 BACKGROUND

• Elliott JA, Jackson S, King S, McHugh R, Docherty NG, Reynolds JV, le Roux CW. Gut Hormone Suppression Increases Food Intake After Esophagectomy With Gastric Conduit Reconstruction. Ann Surg. 2015 Nov;262(5):824-29; discussion 829-30. doi: 10.1097/SLA.0000000000001465.

  PMID: 26583672 RESULT

Related Links

• Wellcome Trust-HRB Clinical Research Facility
• Conway Institute of Biomolecular and Biomedical Research
• St James's Hospital, Dublin
• University of Gothenburg

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Weight Loss; Malnutrition; Endocrine System Diseases

Interventions

Octreotide

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• John V Reynolds, MCh, FRCS

  Department of Surgery, St. James's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Surgical Research Fellow

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 11, 2015
• Study Start: January 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

SE (1); IE (1)