Muscle Wasting in Cancer (MWIC)

NCT03191955 | Completed DMC

• 1 other identifier: Surg2015MWIC
• Study Type: observational
• Target: 282
• Locations: 1 country
• Sites: 1

Brief Summary

One way cancer affects people is through weight loss. During this weight loss (called cachexia), all types of body tissue are lost, but there is a greater rate of muscle loss than fat. Cancer patients with cachexia show decreased quality of life, decreased response to treatment (e.g. chemotherapy), increased complications from surgery, and shorter overall survival. The Investigators aim to identify molecular (and patient) factors within the tissues and bodily fluids of patients with cancer and cachexia in order to identify patients at risk of weight loss, and identify potential therapies. For this, the Investigators aim to take patient samples (muscle, fat, tumour, urine and blood) whilst patients are asleep (general anaesthesia) during their operation to remove the cancer. These samples, and similar samples taken in previous studies, will be analysed in the laboratory. Along with the sample taking, the Investigators aim to perform nutritional assessments of patients before and after surgery to get an accurate picture of their weight loss. This will include simple measurements (e.g. height/weight), and computer reanalysis of their initial diagnostic computed tomography (CT) scans (this study will not require any additional scans for patients). The Investigators also aim to assess how their muscles function, by asking them to perform walk tests and wear a physical activity meter, and assess their quality of life through questionnaires. The Investigators aim to perform nutritional and functional assessments pre-surgery and at 2-3 appointments post-surgery, up to a period of 12 months. At these timepoints, the Investigators also aim to take repeat blood and urine samples, and where possible, one additional thigh muscle biopsy. Repeated assessments allow comparison between "cancer" and "cured" states. The study will take 2 years for patient recruitment. For comparison, the Investigators also aim to examine similar tissue and fluid samples (except tumour) from non-cancer patients who are having surgery for benign conditions (e.g. hernia).

Conditions

Cachexia

Outcome Measures

Primary Outcomes (1)

• Skeletal muscle index of cancer and control patients

  CT measured muscularity performed on preoperative CT scans using validated software

  Analysis of CT scans performed between diagnosis and operation, up to 16 weeks from diagnosis

Secondary Outcomes (5)

• Biochemical analysis of rectus muscle biopsies

  Performed in batches on rectus biopsies taken at time of operation, within 6 months of operation

• Cancer patient 5-year postoperative survival

  Up to 5 years postoperatively

• Measurement of patients BMI

  Performed at clinic between diagnosis and operation, up to 16 weeks from date of diagnosis

• Detailed phenotyping of patients gait speed

  Performed at preoperative clinic, up to 16 weeks from date of diagnosis

• Detailed description of patients quality of life

  Performed at clinic before operation, up to 16 weeks from date of diagnosis

Study Arms (2)

Cancer

Patients with oesophagogastric, hepatobiliary, and colorectal cancer for resectional surgery

Non-cancer

Patients undergoing abdominal operation for non-inflammatory, non-cancer conditions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients referred to the NHS Lothian oesophagogastric, hepatobiliary, and colorectal MDT will be screened for eligibility. In addition, patients attending NHS Lothian outpatient clinics will be screened for eligibility.

You may qualify if:

• Patients identified at multidisciplinary team meetings (MDT) as having oesophagogastric, hepatobiliary, and colorectal cancer suitable for resection
• Patients over 18 years of age
• Patients identified at surgical clinic as being planned for an abdominal operation for a non-cancer, non-inflammatory condition

You may not qualify if:

• Patients with inflammatory conditions or other condition other than cancer that might cause muscle wasting
• Patients without the capacity to consent
• Members of vulnerable groups
• Patients not undergoing abdominal surgery
• Patients undergoing totally minimally invasive (laparoscopic) surgery, with no open or hand-assisted component affording easy access to rectus muscle biopsy

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• Novartis: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Lothian, EH16 4SA, United Kingdom

Location

Related Publications (33)

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  PMID: 21986910 BACKGROUND

• Awad S, Tan BH, Cui H, Bhalla A, Fearon KC, Parsons SL, Catton JA, Lobo DN. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr. 2012 Feb;31(1):74-7. doi: 10.1016/j.clnu.2011.08.008. Epub 2011 Aug 27.

  PMID: 21875767 BACKGROUND

• Khal J, Hine AV, Fearon KC, Dejong CH, Tisdale MJ. Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int J Biochem Cell Biol. 2005 Oct;37(10):2196-206. doi: 10.1016/j.biocel.2004.10.017. Epub 2004 Dec 7.

  PMID: 16125116 BACKGROUND

• Eley HL, Skipworth RJ, Deans DA, Fearon KC, Tisdale MJ. Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients. Br J Cancer. 2008 Jan 29;98(2):443-9. doi: 10.1038/sj.bjc.6604150. Epub 2007 Dec 18.

  PMID: 18087277 BACKGROUND

• Stephens NA, Gallagher IJ, Rooyackers O, Skipworth RJ, Tan BH, Marstrand T, Ross JA, Guttridge DC, Lundell L, Fearon KC, Timmons JA. Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia. Genome Med. 2010 Jan 15;2(1):1. doi: 10.1186/gm122.

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• Johns N, Stephens NA, Preston T. Muscle protein kinetics in cancer cachexia. Curr Opin Support Palliat Care. 2012 Dec;6(4):417-23. doi: 10.1097/SPC.0b013e328359e6dd.

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• Johns N, Stephens NA, Fearon KC. Muscle wasting in cancer. Int J Biochem Cell Biol. 2013 Oct;45(10):2215-29. doi: 10.1016/j.biocel.2013.05.032. Epub 2013 Jun 11.

  PMID: 23770121 BACKGROUND

• Skipworth RJ, Stewart GD, Bhana M, Christie J, Sturgeon CM, Guttridge DC, Cronshaw AD, Fearon KC, Ross JA. Mass spectrometric detection of candidate protein biomarkers of cancer cachexia in human urine. Int J Oncol. 2010 Apr;36(4):973-82. doi: 10.3892/ijo_00000577.

  PMID: 20198343 BACKGROUND

• Stephens NA, Skipworth RJ, Fearon KC. Cachexia, survival and the acute phase response. Curr Opin Support Palliat Care. 2008 Dec;2(4):267-74. doi: 10.1097/SPC.0b013e3283186be2.

  PMID: 19060563 BACKGROUND

• Tan BH, Fladvad T, Braun TP, Vigano A, Strasser F, Deans DA, Skipworth RJ, Solheim TS, Damaraju S, Ross JA, Kaasa S, Marks DL, Baracos VE, Skorpen F, Fearon KC; European Palliative Care Research Collaborative. P-selectin genotype is associated with the development of cancer cachexia. EMBO Mol Med. 2012 Jun;4(6):462-71. doi: 10.1002/emmm.201200231. Epub 2012 Apr 4.

  PMID: 22473907 BACKGROUND

• Brzeszczynska J, Johns N, Schilb A, Degen S, Degen M, Langen R, Schols A, Glass DJ, Roubenoff R, Greig CA, Jacobi C, Fearon KCh, Ross JA. Loss of oxidative defense and potential blockade of satellite cell maturation in the skeletal muscle of patients with cancer but not in the healthy elderly. Aging (Albany NY). 2016 Aug;8(8):1690-702. doi: 10.18632/aging.101006.

  PMID: 27454226 BACKGROUND

• Fearon KC. Cancer cachexia and fat-muscle physiology. N Engl J Med. 2011 Aug 11;365(6):565-7. doi: 10.1056/NEJMcibr1106880. No abstract available.

  PMID: 21830971 BACKGROUND

• Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, Gorkiewicz G, Tamilarasan KP, Kumari P, Trauner M, Zimmermann R, Vesely P, Haemmerle G, Zechner R, Hoefler G. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science. 2011 Jul 8;333(6039):233-8. doi: 10.1126/science.1198973. Epub 2011 Jun 16.

  PMID: 21680814 BACKGROUND

• Mracek T, Stephens NA, Gao D, Bao Y, Ross JA, Ryden M, Arner P, Trayhurn P, Fearon KC, Bing C. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients. Br J Cancer. 2011 Feb 1;104(3):441-7. doi: 10.1038/sj.bjc.6606083. Epub 2011 Jan 18.

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• Skipworth RJ, Husi H, Ross JA. How close are we to finding noninvasive markers for upper GI tract cancer? Future Oncol. 2011 Oct;7(10):1121-4. doi: 10.2217/fon.11.90. No abstract available.

  PMID: 21992724 BACKGROUND

• Husi H, Barr JB, Skipworth RJ, Stephens NA, Greig CA, Wackerhage H, Barron R, Fearon KC, Ross JA. The Human Urinary Proteome Fingerprint Database UPdb. Int J Proteomics. 2013;2013:760208. doi: 10.1155/2013/760208. Epub 2013 Oct 9.

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• Husi H, Skipworth RJ, Cronshaw A, Stephens NA, Wackerhage H, Greig C, Fearon KC, Ross JA. Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer. Proteomics Clin Appl. 2015 Jun;9(5-6):586-96. doi: 10.1002/prca.201400111. Epub 2015 May 8.

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• Deans DA, Tan BH, Wigmore SJ, Ross JA, de Beaux AC, Paterson-Brown S, Fearon KC. The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer. Br J Cancer. 2009 Jan 13;100(1):63-9. doi: 10.1038/sj.bjc.6604828.

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• Deans DA, Wigmore SJ, Gilmour H, Paterson-Brown S, Ross JA, Fearon KC. Elevated tumour interleukin-1beta is associated with systemic inflammation: A marker of reduced survival in gastro-oesophageal cancer. Br J Cancer. 2006 Dec 4;95(11):1568-75. doi: 10.1038/sj.bjc.6603446. Epub 2006 Nov 7.

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• Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009 Nov 15;15(22):6973-9. doi: 10.1158/1078-0432.CCR-09-1525. Epub 2009 Nov 3.

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Biospecimen

Retention: SAMPLES WITH DNA

Rectus Muscle Quadriceps Femoris Muscle Tumour Subcutaneous fat Intra-abdominal fat Blood Urine

MeSH Terms

Conditions

Cachexia

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness

Study Officials

• Michael I Ramage, MBChB

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 19, 2017
• Study Start: November 26, 2015
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)