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

Study Overview
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Brief Summary
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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.

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

Conditions
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Esophageal Neoplasms, Stomach Neoplasms, Weight Loss, Malnutrition, Pancreatic Neoplasms, Duodenal Neoplasms

Intervention / Treatment
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* Drug: Octreotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esophagectomy<br>Double-blind single dose octreotide-placebo crossover | Drug: Octreotide<br>* Single dose 100mcg octreotide acetate (1mL), subcutaneously to the lower abdomen<br>* Other names: Sandostatin;Drug: Placebo<br>* Single dose 0.9% saline (1mL), subcutaneously to the lower abdomen<br>|
| Experimental: Gastrectomy<br>Double-blind single dose octreotide-placebo crossover | Drug: Octreotide<br>* Single dose 100mcg octreotide acetate (1mL), subcutaneously to the lower abdomen<br>* Other names: Sandostatin;Drug: Placebo<br>* Single dose 0.9% saline (1mL), subcutaneously to the lower abdomen<br>|
| Active Comparator: Unoperated healthy control<br>Double-blind single dose octreotide-placebo crossover | Drug: Octreotide<br>* Single dose 100mcg octreotide acetate (1mL), subcutaneously to the lower abdomen<br>* Other names: Sandostatin;Drug: Placebo<br>* Single dose 0.9% saline (1mL), subcutaneously to the lower abdomen<br>|
| Experimental: Pancreaticoduodenectomy<br>Double-blind single dose octreotide-placebo crossover | Drug: Octreotide<br>* Single dose 100mcg octreotide acetate (1mL), subcutaneously to the lower abdomen<br>* Other names: Sandostatin;Drug: Placebo<br>* Single dose 0.9% saline (1mL), subcutaneously to the lower abdomen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progressive ratio task breakpoint for a sweet-fat reward |  | 3 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of rewards consumed |  | 3 hours | 
| Subjective symptom score |  | 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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