Assessing Timing of Enteral Feeding Support in Esophageal Cancer Patients on Muscle functTion and Survival

NCT03676478 | Terminated DMC

• 4 other identifiers: S616652018-002891-41116000000382T002018N
• Study Type: interventional
• Target: 239
• Locations: 1 country
• Sites: 1

Brief Summary

The surgical stress of an esophagectomy causes a detrimental impact on the physiological response of the body. In this perspective, one could question whether the current feeding regimens of starting early nutritional support at postoperative day (POD) 1 have a similar negative impact on the muscle mass as documented in critically ill patients. This study will introduce relative starvation in the early days following esophagectomy compared to the current regimen of early enteral nutritional support. The research team aims to investigate whether the negative impact on muscle mass and muscle function might be reduced, which should result in enhanced postoperative recovery. The final result of the study will be a well-documented and scientifically substantiated nutritional regimen for patients who underwent an esophagectomy for cancer.

Conditions

Nutrition Aspect of Cancer; Esophageal Cancer; Postoperative Complications; Muscle Weakness; Sarcopenia; Jejunostomy; Complications

Outcome Measures

Primary Outcomes (1)

• Functional recovery (6mWD - 6-minute Walked Distance)

  detect a difference in walked distance evaluated by means of a 6-minute walk test

  5±1 weeks postoperative

Secondary Outcomes (2)

• Days alive outside hospital

  90 days postoperative

• Global Health status score

  5+/-1 week postoperative

Other Outcomes (27)

• Occurrence of readmission

  assessed upto 1 year postoperative

• Variation in 6-minute walked distance

  discharge and 90 days postoperative

• 90-day mortality

  90 days postoperative

Study Arms (2)

start enteral support @ POD1

NO INTERVENTION

The standard of care (SoC) in our department consists of enteral nutritional support of maximum 1000 kilocalories (kCal) through a peroperatively placed jejunostomy feeding tube started at POD 1. Oral caloric intake is resumed at POD 4.

delayed start enteral support @ POD5

ACTIVE COMPARATOR

As study intervention (INT), a period of caloric restriction is set by starting the enteral nutritional support later, at POD 5. Oral caloric intake is resumed at POD 4, similarly as in the control group. This intervention results in a relative caloric defect of more than 4.000 kCal in the immediate postoperative course.

Other: delayed start enteral support @ POD5

Interventions

delayed start enteral support @ POD5 OTHER

instead of caloric suppletion, participants will receive mls of water over the jejunostomy feeding tube daily equivalent to the rate of increase of infusion of the control group as to preserve the same amount of fluid administration through the GI route as the control group. This is continued until POD5 12.00h when enteral feeding is started according to the incremental regimen as defined for the SOC group. During the intervention, water is used as to maximize stimulation of the enteral route, however without giving nutritional support and need to prolong iv-infusion for maintaining the fluid balance in the participants. Also subjects in this interventional arm will end up with a caloric suppletion of 1.000kCal/24h by the end of postoperative day 7.

Also known as: delayed start / caloric restriction

delayed start enteral support @ POD5

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Candidates for surgical resection with a curative intent, admitted to our Department.
• Able to understand the study information in Dutch or French and tasks related to the study measurements provided by the researchers.
• Able to consent.
• Patients with cancer of the gastroesophageal junction (GEJ), distal, mid- and proximal thoracic esophagus.
• Patients with early as well as advanced clinical stage esophageal cancer: from clinical stages cT1N0 over cT2+ N+ or cT3 Nx after neo-adjuvant therapy or at the time of staging as a candidate for primary surgery.
• Histology preop: Squamous or adenocarcinoma.
• All access: (robotic assisted) minimal invasive (thoracoscopy \& laparoscopy) approach, left thoraco-abdominal incision, hybrid esophageal resection or R thoracotomy + laparotomy
• Partial or subtotal esophagectomy.
• Reconstruction by gastric conduit.
• All anastomoses (intrathoracic or cervical).
• Women of child bearing age with esophageal cancer can be included.

You may not qualify if:

• Patients in a definitive chemoradiation protocol, or undergoing rescue resection following definitive chemoradiotherapy.
• Patients expected to die within 12 hours (=moribund patients).
• Patients transferred from another institute after esophageal resection with an established nutritional therapy.
• Patients with a cT4b tumor after neo-adjuvant therapy.
• Patients who are at the time of surgery deemed unresectable or found to be unresectable during surgery.
• Patients with a R2-resection.
• Patients with metastasis at the time of clinical staging.
• Patients undergoing transhiatal resection of the esophagus.
• Patients undergoing total gastrectomy
• Patients undergoing an esophageal resection or esophageal bypass as palliative treatment
• Patients with tumors in the cervical esophagus with a distance less than 3cm from the cricopharyngeal sphincter.
• Patients with pharyngeal cancer undergoing (laryngo-)pharyngectomy with gastric pull-up
• Need for colonic or jejunal interposition
• Patients with a second synchronous malignancy
• Patients with inflammatory bowel disease (as this might interfere with caloric uptake in the small bowel)

Sponsors & Collaborators

• University Hospital, Gasthuisberg: lead
• Research Foundation Flanders: collaborator
• Kom Op Tegen Kanker: collaborator
• KU Leuven: collaborator

Study Sites (1)

University Hospitals Leuven, dept. of Thoracic Surgery

Leuven, 3000, Belgium

Location

Related Publications (10)

• Van Veer H, Moons J, Darling G, Lerut T, Coosemans W, Waddell T, De Leyn P, Nafteux P. Validation of a new approach for mortality risk assessment in oesophagectomy for cancer based on age- and gender-corrected body mass index. Eur J Cardiothorac Surg. 2015 Oct;48(4):600-7. doi: 10.1093/ejcts/ezu503. Epub 2015 Jan 5.

  PMID: 25564215 BACKGROUND

• Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):506-17. doi: 10.1056/NEJMoa1102662. Epub 2011 Jun 29.

  PMID: 21714640 BACKGROUND

• Willcutts KF, Chung MC, Erenberg CL, Finn KL, Schirmer BD, Byham-Gray LD. Early Oral Feeding as Compared With Traditional Timing of Oral Feeding After Upper Gastrointestinal Surgery: A Systematic Review and Meta-analysis. Ann Surg. 2016 Jul;264(1):54-63. doi: 10.1097/SLA.0000000000001644.

  PMID: 26779983 BACKGROUND

• Low DE, Alderson D, Cecconello I, Chang AC, Darling GE, D'Journo XB, Griffin SM, Holscher AH, Hofstetter WL, Jobe BA, Kitagawa Y, Kucharczuk JC, Law SY, Lerut TE, Maynard N, Pera M, Peters JH, Pramesh CS, Reynolds JV, Smithers BM, van Lanschot JJ. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg. 2015 Aug;262(2):286-94. doi: 10.1097/SLA.0000000000001098.

  PMID: 25607756 BACKGROUND

• Rabinovich RA, Louvaris Z, Raste Y, Langer D, Van Remoortel H, Giavedoni S, Burtin C, Regueiro EM, Vogiatzis I, Hopkinson NS, Polkey MI, Wilson FJ, Macnee W, Westerterp KR, Troosters T; PROactive Consortium. Validity of physical activity monitors during daily life in patients with COPD. Eur Respir J. 2013 Nov;42(5):1205-15. doi: 10.1183/09031936.00134312. Epub 2013 Feb 8.

  PMID: 23397303 BACKGROUND

• Bosy-Westphal A, Schautz B, Later W, Kehayias JJ, Gallagher D, Muller MJ. What makes a BIA equation unique? Validity of eight-electrode multifrequency BIA to estimate body composition in a healthy adult population. Eur J Clin Nutr. 2013 Jan;67 Suppl 1:S14-21. doi: 10.1038/ejcn.2012.160.

  PMID: 23299866 BACKGROUND

• Leelarathna L, Wilmot EG. Flash forward: a review of flash glucose monitoring. Diabet Med. 2018 Apr;35(4):472-482. doi: 10.1111/dme.13584. Epub 2018 Feb 27.

  PMID: 29356072 BACKGROUND

• Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol (1985). 2000 Jul;89(1):104-10. doi: 10.1152/jappl.2000.89.1.104.

  PMID: 10904041 BACKGROUND

• Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB, Baracos VE. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 2013 Apr 20;31(12):1539-47. doi: 10.1200/JCO.2012.45.2722. Epub 2013 Mar 25.

  PMID: 23530101 BACKGROUND

• Tarnopolsky MA, Pearce E, Smith K, Lach B. Suction-modified Bergstrom muscle biopsy technique: experience with 13,500 procedures. Muscle Nerve. 2011 May;43(5):717-25. doi: 10.1002/mus.21945. Epub 2011 Apr 1.

  PMID: 21462204 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms; Postoperative Complications; Muscle Weakness; Sarcopenia

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Muscular Atrophy; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Philippe Nafteux, MD, PhD

  Department of Thoracic Surgery

  STUDY CHAIR

• Lieven P Depypere, MD, PhD

  Department of Thoracic Surgery

  PRINCIPAL INVESTIGATOR

• Michaël Casaer, MD, PhD

  Department of Intensive Care Medicine

  STUDY CHAIR

• Hans GL Van Veer, MD

  Department of Thoracic Surgery

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study is single blinded at the level of outcome assessment. As in the postoperative setting it will be clear which subject is in the delayed enteral feeding group, masking cannot be performed for participants, care providers and the investigators. Therefore the study is considered to be open label, but single blinded for the primary outcome analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FEBS-OGS

Model Details: Single blinded (for outcome), open label, prospective, randomized, controlled, parallel-group designed interventional study

Study Record Dates

• First Submitted: July 18, 2018
• First Posted: September 18, 2018
• Study Start: March 25, 2019
• Primary Completion: May 25, 2025
• Study Completion: December 2, 2025
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)