Resection of the Esophagus and Subsequent Weight Loss (REWARD)

The Effect of Clinical Treatment for Unintentional Weight Loss on Food Reward and Appetitive Behaviour in Patients Who Have Lost >10% of Their Body Weight After Undergoing Curative Surgery for Oesophageal Cancer

The investigators aim to ascertain how food reward signals and eating behaviour relates to the gut-brain pathway in weight-losing patients after curative surgery for oesophageal cancer, and how this pathway responds to clinical treatment for this unintentional weight loss. The primary outcomes are the blood oxygen level dependent (BOLD) signal on functional MRI (fMRI), and the breakpoint during the progressive ratio task (PRT - a measure of eating behaviour), how these differ in response to multiple clinical treatment options, as well as how they relate to weight gain while on treatment.

Study Overview

• Status: Terminated
• Conditions: Esophageal Cancer; Weight Gain; Eating Behavior; Food Reward
• Intervention / Treatment: Other: Clinical treatment

Detailed Description

The incidence of cancer of the oesophagus (food pipe) is increasing. Improvements in treatment strategies have resulted in more people who remain free from cancer recurrence in the long term following treatment.

Surgery is the cornerstone of treatment for patients with oesophageal cancer, but while surgical removal of the tumour (oesophagectomy) may offer the best chance of cure, these are major operations associated with specific long term complications. Poor appetite, weight loss and nutritional impairment are common problems among patients who attain long-term cancer remission and cure after surgery.

A new clinic has been established to treat patients who are in remission but who have lost more than 10% of their body weight secondary to the effects of the surgery and struggling to regain weight. These patients will be treated as per standard of care with medications to aid weight gain.

The investigators are interested to conduct research into how the reward value of food changes during the clinical treatment pathway. The hypothesis is that there will be an increased reward response to food after medication use, the magnitude of which will correlate with weight gain. To assess this, patients who are already part of this clinic will be approached to have fMRI that can demonstrate changes in brain reward centres as well as a Progressive Ratio Task, which is a direct measure of appetitive behaviour. Changes in brain reward centre responses and appetitive behaviour will be correlated with changes in weight after pharmacotherapy. This may further inform future clinical protocols to provide improved precision medicine.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland
    • Conway Institute, UCD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

A cohort of post-esophagectomy patients at least 1 year after curative surgery, but struggling with unintentional weight loss of at least 10% baseline body weight, and thus candidates for clinical treatment.

Description

Inclusion Criteria:

1. History of esophagectomy with gastric conduit reconstruction
2. Recurrence-free at least 12 months post-operatively
3. Weight loss ≥10% from premorbid weight, or requiring ongoing caloric supplementation
4. Due to undergo clinical treatment for weight loss with Sandostatin or Mirtazapine

Exclusion Criteria:

1. Pregnancy, breastfeeding
2. Significant and persistent chemoradiotherapy and/or surgical complication
3. Other active malignancy
4. Exocrine pancreatic insufficiency detected using fecal elastase
5. Uncontrolled diabetes mellitus
6. Significant psychiatric disorder or cognitive decline or communication impairment limiting capacity to provide informed consent
7. Severe dysphagia
8. Other disease or medication which may impact gut hormone physiology
9. History of significant food allergy, certain dietary restrictions
10. Any definite contraindication to somatostatin analogue administration
11. Claustrophobia, or any absolute contraindication to MRI scanning
12. Metallic implants, precluding fMRI

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sandostatin; This cohort will be the group who are undergoing routine clinical treatment with a long-acting somatostatin analogue to minimise abnormal gut hormone signalling, and thus reduce early satiety.	Other: Clinical treatment; Patients undergo clinical treatment as indicated, they are studied before and after.
Mirtazapine; This cohort will be the group who are undergoing routine clinical treatment with a tetracyclic antidepressant to stimulate appetite.	Other: Clinical treatment; Patients undergo clinical treatment as indicated, they are studied before and after.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BOLD signal	Measure of food reward on fMRI	Before and after 4 weeks of clinical treatment
Change in breakpoint at PRT	Measure of drive to eat	Before and after 4 weeks of clinical treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of weight change during treatment with BOLD signal changes	Relationship of food reward changes to weight gain	Before and after 4 weeks of clinical treatment
Correlation of weight change during treatment with PRT breakpoint changes	Relationship of eating behaviour changes to weight gain	Before and after 4 weeks of clinical treatment

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: University College Dublin; St. James's Hospital, Ireland

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Esophagectomy; Gut hormones; Unintentional weight loss
• Additional Relevant MeSH Terms: Body Weight Changes; Weight Loss; Body Weight; Weight Gain
• Other Study ID Numbers: CRFSJ0148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No