The Role of the Muscle-nervous System Interface in Cancer Cachexia

NCT03477721 | Unknown

• 1 other identifier: NUMANCAN
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Sarcopenia is an important component of cachexia associated with cancer, and their high incidence in cancer patients emphasizes the need for a better understanding of its mechanisms, which can result in better therapeutic interventions to reverse this situation and improve the prognosis. Our hypothesis is that the plasma concentration of IL-6 and c-terminal agrin is directly correlated with the loss of muscle mass and development of cachexia.

Conditions

Cachexia; Cancer; Sarcopenia

Keywords

Agrin Fragment C-terminus (CAF)

Outcome Measures

Primary Outcomes (4)

• Agrin fragment c-terminus CAF in cancer and cancer cachexia

  To measure the contents of agrin fragment c-terminus (CAF) in plasma of patient with cancer and cancer cachexia.

  1 month

• Agrin fragment c-terminus CAF in cancer sarcopenia

  To analyze correlation between Agrin fragment c-terminus CAF and the lean body mass (CT-scan estimated) of patients with cancer and with cancer cachexia.

  1 month

• Agrin fragment c-terminus CAF and IL-6 levels

  To correlate levels of agrin fragment c-terminus (CAF) and IL-6 plasma levels in patients with cancer and with cancer cachexia.

  1 month

• Agrin fragment c-terminus (CAF) and IL-6 and lean body mass

  To correlate levels of agrin fragment c-terminus (CAF) and IL-6 with the lean body mass

  1 month

Study Arms (2)

Group with cancer cachexia (CTB)

For diagnosis of cachexia it will be used the following criteria (Evans et al., 2008)

Group without cancer cachexia (TB)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Oure sample will be selected between cancer patient of Rome Umberto I Hospital

You may qualify if:

• cancer diagnosis

You may not qualify if:

• continuously use of anti-inflammatory medications;
• present renal and/or liver failure,
• AIDS,
• inflammatory bowel disease or chronic inflammatory processes not related to cachexia.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Department of Clinical Medicine, Sapienza University of Rome

Rome, 00185, Italy

RECRUITING

Related Publications (23)

• Argiles JM, Alvarez B, Lopez-Soriano FJ. The metabolic basis of cancer cachexia. Med Res Rev. 1997 Sep;17(5):477-98. doi: 10.1002/(sici)1098-1128(199709)17:53.0.co;2-r. No abstract available.

  PMID: 9276862 BACKGROUND

• Argiles JM, Busquets S, Toledo M, Lopez-Soriano FJ. The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 2009 Dec;3(4):263-8. doi: 10.1097/SPC.0b013e3283311d09.

  PMID: 19713854 BACKGROUND

• Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001 Feb 17;357(9255):539-45. doi: 10.1016/S0140-6736(00)04046-0.

  PMID: 11229684 BACKGROUND

• Batista ML Jr, Peres SB, McDonald ME, Alcantara PS, Olivan M, Otoch JP, Farmer SR, Seelaender M. Adipose tissue inflammation and cancer cachexia: possible role of nuclear transcription factors. Cytokine. 2012 Jan;57(1):9-16. doi: 10.1016/j.cyto.2011.10.008. Epub 2011 Nov 17.

  PMID: 22099872 BACKGROUND

• Belizario JE, Fontes-Oliveira CC, Borges JP, Kashiabara JA, Vannier E. Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6. Springerplus. 2016 May 13;5:619. doi: 10.1186/s40064-016-2197-2. eCollection 2016.

  PMID: 27330885 BACKGROUND

• Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD. Cachexia: a new definition. Clin Nutr. 2008 Dec;27(6):793-9. doi: 10.1016/j.clnu.2008.06.013. Epub 2008 Aug 21.

  PMID: 18718696 BACKGROUND

• Fan Y, Mao R, Yang J. NF-kappaB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell. 2013 Mar;4(3):176-85. doi: 10.1007/s13238-013-2084-3. Epub 2013 Mar 13.

  PMID: 23483479 BACKGROUND

• Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. doi: 10.1016/S1470-2045(10)70218-7. Epub 2011 Feb 4.

  PMID: 21296615 BACKGROUND

• Fearon KC, Moses AG. Cancer cachexia. Int J Cardiol. 2002 Sep;85(1):73-81. doi: 10.1016/s0167-5273(02)00235-8.

  PMID: 12163211 BACKGROUND

• Fearon KC, Voss AC, Hustead DS; Cancer Cachexia Study Group. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr. 2006 Jun;83(6):1345-50. doi: 10.1093/ajcn/83.6.1345.

  PMID: 16762946 BACKGROUND

• Gonzalez-Freire M, de Cabo R, Studenski SA, Ferrucci L. The Neuromuscular Junction: Aging at the Crossroad between Nerves and Muscle. Front Aging Neurosci. 2014 Aug 11;6:208. doi: 10.3389/fnagi.2014.00208. eCollection 2014.

  PMID: 25157231 BACKGROUND

• Hettwer S, Dahinden P, Kucsera S, Farina C, Ahmed S, Fariello R, Drey M, Sieber CC, Vrijbloed JW. Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients. Exp Gerontol. 2013 Jan;48(1):69-75. doi: 10.1016/j.exger.2012.03.002. Epub 2012 Mar 11.

  PMID: 22433628 BACKGROUND

• Kalinkovich A, Livshits G. Sarcopenia--The search for emerging biomarkers. Ageing Res Rev. 2015 Jul;22:58-71. doi: 10.1016/j.arr.2015.05.001. Epub 2015 May 8.

  PMID: 25962896 BACKGROUND

• Kern KA, Norton JA. Cancer cachexia. JPEN J Parenter Enteral Nutr. 1988 May-Jun;12(3):286-98. doi: 10.1177/0148607188012003286.

  PMID: 3292798 BACKGROUND

• Kujawski M, Kortylewski M, Lee H, Herrmann A, Kay H, Yu H. Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J Clin Invest. 2008 Oct;118(10):3367-77. doi: 10.1172/JCI35213.

  PMID: 18776941 BACKGROUND

• Kumar NB, Kazi A, Smith T, Crocker T, Yu D, Reich RR, Reddy K, Hastings S, Exterman M, Balducci L, Dalton K, Bepler G. Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol. 2010 Dec;11(3-4):107-17. doi: 10.1007/s11864-010-0127-z.

  PMID: 21128029 BACKGROUND

• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436-44. doi: 10.1038/nature07205.

  PMID: 18650914 BACKGROUND

• Mignogna MD, Fedele S, Lo Russo L, Lo Muzio L, Bucci E. Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence ? Oral Oncol. 2004 Feb;40(2):120-30. doi: 10.1016/j.oraloncology.2003.08.001.

  PMID: 14693234 BACKGROUND

• Okada F. Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms. Yonago Acta Med. 2014 Jun;57(2):65-72. Epub 2014 Jul 30.

  PMID: 25324587 BACKGROUND

• Roxburgh CS, McMillan DC. Cancer and systemic inflammation: treat the tumour and treat the host. Br J Cancer. 2014 Mar 18;110(6):1409-12. doi: 10.1038/bjc.2014.90. Epub 2014 Feb 18.

  PMID: 24548867 BACKGROUND

• Scherbakov N, Knops M, Ebner N, Valentova M, Sandek A, Grittner U, Dahinden P, Hettwer S, Schefold JC, von Haehling S, Anker SD, Joebges M, Doehner W. Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation. J Cachexia Sarcopenia Muscle. 2016 Mar;7(1):60-7. doi: 10.1002/jcsm.12068. Epub 2015 Oct 27.

  PMID: 27066319 BACKGROUND

• Tisdale MJ. Cancer cachexia. Curr Opin Gastroenterol. 2010 Mar;26(2):146-51. doi: 10.1097/MOG.0b013e3283347e77.

  PMID: 19918173 BACKGROUND

• Srdic D, Plestina S, Sverko-Peternac A, Nikolac N, Simundic AM, Samarzija M. Cancer cachexia, sarcopenia and biochemical markers in patients with advanced non-small cell lung cancer-chemotherapy toxicity and prognostic value. Support Care Cancer. 2016 Nov;24(11):4495-502. doi: 10.1007/s00520-016-3287-y. Epub 2016 May 28.

  PMID: 27236439 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples: determination of: serum C-reactive protein, albumin, creatinine and haemoglobin concentrations. Agrin fragment c-terminus and IL-6 will be carried out using specific ELISA kits.

MeSH Terms

Conditions

Cachexia; Neoplasms; Sarcopenia

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Study Officials

• Alessandro Laviano, MD

  Department of Clinical Medicine, Sapienza University of Rome, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laviano Alessandro

CONTACT

+390649973902; alessandro.laviano@uniroma1.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Alessandro Laviano, MD associate professor of Internal Medicine

Study Record Dates

• First Submitted: March 11, 2018
• First Posted: March 26, 2018
• Study Start: March 16, 2018
• Primary Completion: April 16, 2018
• Study Completion: April 30, 2018
• Last Updated: March 26, 2018

Record last verified: 2018-03

Locations

IT (1)