Clinical trial NCT03377660: Resection of the Esophagus and Subsequent Weight Loss
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
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Esophageal Cancer
Weight Gain
Eating Behavior
Food Reward
Keywords: Esophagectomy
Unintentional weight loss
Gut hormones
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University College Dublin
name: St. James's Hospital, Ireland
First posted: 2017-12-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in BOLD signal
timeFrame: Before and after 4 weeks of clinical treatment
measure: Change in breakpoint at PRT
timeFrame: Before and after 4 weeks of clinical treatment
Secondary outcomes:
measure: Correlation of weight change during treatment with BOLD signal changes
timeFrame: Before and after 4 weeks of clinical treatment
measure: Correlation of weight change during treatment with PRT breakpoint changes
timeFrame: Before and after 4 weeks of clinical treatment
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Conway Institute, UCD
Study officials:
References: