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Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery (EndoGut)

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ClinicalTrials.gov Identifier: NCT03734627
Recruitment Status : Enrolling by invitation
First Posted : November 8, 2018
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Dr Jessie A Elliott, St. James's Hospital, Ireland

Tracking Information
First Submitted Date November 6, 2018
First Posted Date November 8, 2018
Last Update Posted Date November 8, 2018
Actual Study Start Date July 1, 2016
Estimated Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 6, 2018)
Area under the curve for paracetamol at 30 minutes after a 400kcal mixed meal stimulus [ Time Frame: 30 minutes post meal ]
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: November 6, 2018)
  • Peak paracetamol level [ Time Frame: Within 300 minutes post meal ]
  • GLP-1 area under the curve over 300 minutes after a 400kcal mixed meal stimulus [ Time Frame: Within 300 minutes post meal ]
  • Glucose area under the curve over 300 minutes after a 400kcal mixed meal stimulus [ Time Frame: Within 300 minutes post meal ]
  • Insulin area under the curve over 300 minutes after a 400kcal mixed meal stimulus [ Time Frame: Within 300 minutes post meal ]
  • Visual analogue scales [ Time Frame: Within 300 minutes post meal ]
  • EORTC health related quality of life [ Time Frame: At one year post surgery, on the day of assessment ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 6, 2018)
  • Duodenal enteroendocrine cell density [ Time Frame: At one year post surgery, on the day of assessment ]
  • Duodenal enteroendocrine L-cell density [ Time Frame: At one year post surgery, on the day of assessment ]
  • Duodenal enteroendocrine cell mRNA expression profile [ Time Frame: At one year post surgery, on the day of assessment ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery
Official Title Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery
Brief Summary

The incidence of oesophagogastric cancer has increased by 400% since the 1970s in Ireland and the United Kingdom. In addition, refinement of perioperative management and the now widespread use of multimodal protocols for patients with locally advanced disease have significantly improved outcomes for patients with oesophagogastric cancer treatable with curative intent. Despite significant advances in chemoradiotherapy, surgical resection remains the primary curative option.

Unintentional weight loss and nutritional complications represent serious concerns for patients after radical resection, even among those who remain free from recurrent disease in the long-term. A study from the Swedish Esophageal and Cardia Cancer Registry reported a mean three year weight loss of 10.8% among disease-free patients, with 33.8% of this cohort demonstrating malnutrition at three years post-oesophagectomy.

Mechanisms contributing to weight loss for disease-free patients after upper gastrointestinal surgery are poorly understood, however an association between increasing magnitude of weight loss and the presence of increased satiety is described. Our recent studies at SJH have demonstrated four fold elevated postprandial satiety gut hormone concentrations after oesophagectomy, compared with baseline preoperative values. Postprandial gut hormone levels correlate significantly with postprandial symptoms and altered appetite at 3 months postoperatively, and with body weight loss at 2 years postoperatively. However, the mechanism leading to exaggerated postprandial gut hormone production after upper gastrointestinal surgery is poorly understood, limiting targeted therapeutic options.

In this study, we aim to characterise the role of altered nutrient transit and enteroendocrine cell function in the pathophysiology of excessive post-prandial gut hormone responses after upper gastrointestinal surgery. To do this, we will measure the gut hormone response to a standardised 400 kcal meal, as per previous studies, while concurrently assessing gastrointestinal transit time, and enteroendocrine cell morphology and function. In this way, we will determine whether the magnitude of the postprandial gut hormone response correlates with the rate of nutrient transit into the enteroendocrine L-cell rich small intestine, and whether enteroendocrine cell adaptation occurs after oesophagectomy.

Furthermore, we have previously observed that gut hormone suppression using octreotide is associated with increased ad libitum among subjects after upper gastrointestinal cancer surgery (Elliott JA et al, Annals of Surgery, 2015). The mechanism of action of octreotide may relate to SSTR-5-mediated negative feedback to the enteroendocrine L-cell, but this medication may additionally reduce enteroendocrine L-cell responses through its inhibitory effect on gastrointestinal motility - reducing the rapidity with which nutrients are delivered to the small intestine - and small intestinal nutrient sensing via inhibition of the Na+-dependent glucose transporter SGLT-18-10. Through conduction of this double-blind, randomised, placebo-controlled crossover study, we aim to establish the mechanism of action of octreotide-mediated increased food intake in patients after gastrointestinal surgery. This may inform the design of future targeted interventions for this patient group.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
  • Plasma
  • Serum
  • Duodenal biopsies
Sampling Method Probability Sample
Study Population Patients at least 9 months post upper gastrointestinal surgery and age-, weight- and sex-matched control subjects with gastroesophageal reflux disease or non-dysplastic Barrett's oeosophagus.
Condition
  • Esophageal Cancer
  • Nutrition Disorders
  • Appetite Disorders
  • Dumping Syndrome
  • Delayed Gastric Emptying
  • Surgery
Intervention
  • Drug: Octreotide Acetate
    50mcg octreotide acetate by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge
  • Drug: Saline Solution
    Equivalent volume of 0.9% saline by subcutaneous injection 10 minutes prior to a 400kcal mixed meal challenge
  • Drug: Paracetamol
    Paracetamol 1g by mouth consumed with a 400kcal mixed meal challenge
  • Drug: Sulfasalazine
    1g sulfasalazine by mouth consumed with a 400kcal mixed meal challenge
  • Diagnostic Test: Duodenal biopsy
    Biopsy from the second part of the duodenum taken at routine endoscopic surveillance, undertaken for another clinical indication.
Study Groups/Cohorts
  • Upper Gastrointestinal Surgery - Transit
    Interventions:
    • Drug: Octreotide Acetate
    • Drug: Saline Solution
    • Drug: Paracetamol
    • Drug: Sulfasalazine
  • Control - Transit
    Interventions:
    • Drug: Octreotide Acetate
    • Drug: Saline Solution
    • Drug: Paracetamol
    • Drug: Sulfasalazine
  • Upper Gastrointestinal Surgery - Gut Function
    Intervention: Diagnostic Test: Duodenal biopsy
  • Control - Gut Function
    Intervention: Diagnostic Test: Duodenal biopsy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Enrolling by invitation
Estimated Enrollment
 (submitted: November 6, 2018)
40
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 1, 2019
Estimated Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Patient group:

1. History of upper gastrointestinal surgery at least 9 months previously

Control group:

1. Patients with suspected or confirmed non-dysplastic Barrett's oesophagus or reflux who are age, weight and gender matched to the patient cohort

Exclusion Criteria:

  1. Pregnancy, breastfeeding
  2. Recurrent disease after surgery
  3. Other active malignancy
  4. Significant psychiatric disorder or cognitive decline or communication impairment limiting capacity to provide informed consent
  5. Other disease or medication which may impact gut hormone physiology
  6. Previous upper gastrointestinal resection
  7. Certain allergies or dietary intolerances
  8. Anticoagulants

Patients with contraindications to the study medications (as per www.medicines.ie) will not be automatically excluded, but will be invited to participate in an attenuated protocol where that agent is not given. It is not anticipated that this will be a frequent occurrence, however this strategy will minimise unnecessary participant exclusion.

Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Ireland
Removed Location Countries  
 
Administrative Information
NCT Number NCT03734627
Other Study ID Numbers CRFSJ075 and 0095
2016-02-CA(9) ( Other Identifier: SJH/AMNCH Research Ethics Committee )
2016-03-11(1) ( Other Identifier: SJH/AMNCH Research Ethics Committee )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Dr Jessie A Elliott, St. James's Hospital, Ireland
Study Sponsor St. James's Hospital, Ireland
Collaborators Not Provided
Investigators
Principal Investigator: John V Reynolds, MD FRCS St. James's Hospital, Dublin, Ireland
Principal Investigator: Carel W le Roux, FRCP FRCPath PhD Conway Institute of Biomolecular and Biomedical Research
PRS Account St. James's Hospital, Ireland
Verification Date November 2018