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The Effect of Satiety Gut Hormone Modulation on Appetitive Drive After Upper Gastrointestinal Surgery

Primary Purpose

Esophageal Neoplasms, Stomach Neoplasms, Weight Loss

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Octreotide
Placebo
Sponsored by
St. James's Hospital, Ireland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Esophageal Neoplasms focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital
  • Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Experimental

Arm Label

Esophagectomy

Gastrectomy

Unoperated healthy control

Pancreaticoduodenectomy

Arm Description

Double-blind single dose octreotide-placebo crossover

Double-blind single dose octreotide-placebo crossover

Double-blind single dose octreotide-placebo crossover

Double-blind single dose octreotide-placebo crossover

Outcomes

Primary Outcome Measures

Progressive ratio task breakpoint for a sweet-fat reward

Secondary Outcome Measures

Number of rewards consumed
Subjective symptom score

Full Information

First Posted
March 2, 2015
Last Updated
November 6, 2018
Sponsor
St. James's Hospital, Ireland
Collaborators
University College Dublin, University of Dublin, Trinity College, Göteborg University
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1. Study Identification

Unique Protocol Identification Number
NCT02381249
Brief Title
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

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. James's Hospital, Ireland
Collaborators
University College Dublin, University of Dublin, Trinity College, Göteborg University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Esophagectomy
Arm Type
Experimental
Arm Description
Double-blind single dose octreotide-placebo crossover
Arm Title
Gastrectomy
Arm Type
Experimental
Arm Description
Double-blind single dose octreotide-placebo crossover
Arm Title
Unoperated healthy control
Arm Type
Active Comparator
Arm Description
Double-blind single dose octreotide-placebo crossover
Arm Title
Pancreaticoduodenectomy
Arm Type
Experimental
Arm Description
Double-blind single dose octreotide-placebo crossover
Intervention Type
Drug
Intervention Name(s)
Octreotide
Other Intervention Name(s)
Sandostatin
Intervention Description
Single dose 100mcg octreotide acetate (1mL), subcutaneously to the lower abdomen
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single dose 0.9% saline (1mL), subcutaneously to the lower abdomen
Primary Outcome Measure Information:
Title
Progressive ratio task breakpoint for a sweet-fat reward
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
Number of rewards consumed
Time Frame
3 hours
Title
Subjective symptom score
Time Frame
3 hours
Other Pre-specified Outcome Measures:
Title
Sigstad score
Description
Both categorical and continuous
Time Frame
3 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria: 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 Disease-free at least one year post-resection Exclusion criteria: Pregnancy, breastfeeding Significant and persistent chemoradiotherapy and/or surgical complication Other previous upper gastrointestinal surgery Unwell or 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 Requiring adjuvant chemotherapy Contraindication to octreotide administration History of eating disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John V Reynolds, MCh, FRCS
Organizational Affiliation
Department of Surgery, St. James's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Wellcome Trust-Health Research Board Clinical Research Facility, St. James's Hospital
City
Dublin
ZIP/Postal Code
D8
Country
Ireland
Facility Name
Gastrosurgical Laboratory, Sahlgrenska Academy, University of Gothenburg
City
Gothenburg
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
22836034
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.
Results Reference
background
PubMed Identifier
13714876
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.
Results Reference
background
PubMed Identifier
8319842
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.
Results Reference
background
PubMed Identifier
20842361
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.
Results Reference
background
PubMed Identifier
21440118
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.
Results Reference
background
PubMed Identifier
16371744
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.
Results Reference
background
PubMed Identifier
30722001
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.
Results Reference
derived
Links:
URL
http://www.sjhcrf.ie
Description
Wellcome Trust-HRB Clinical Research Facility
URL
http://www.ucd.ie/conway/
Description
Conway Institute of Biomolecular and Biomedical Research
URL
https://medicine.tcd.ie/surgery/
Description
Department of Surgery, Trinity College Dublin and St. James's Hospital

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The Effect of Satiety Gut Hormone Modulation on Appetitive Drive After Upper Gastrointestinal Surgery

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