REWARD: Resection of the Esophagus and Subsequent Weight Loss

Sponsor

Imperial College London (Other)

Overall Status

Recruiting

CT.gov ID

NCT03377660

Collaborator

University College Dublin (Other), St. James's Hospital, Ireland (Other)

Enrollment

Location

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer Weight Gain Eating Behavior Food Reward	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 Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 1, 2018

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

Change in BOLD signal [Before and after 4 weeks of clinical treatment]
Measure of food reward on fMRI
Change in breakpoint at PRT [Before and after 4 weeks of clinical treatment]
Measure of drive to eat

Secondary Outcome Measures

Correlation of weight change during treatment with BOLD signal changes [Before and after 4 weeks of clinical treatment]
Relationship of food reward changes to weight gain
Correlation of weight change during treatment with PRT breakpoint changes [Before and after 4 weeks of clinical treatment]
Relationship of eating behaviour changes to weight gain

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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