Cachexia; Cancer; SarcopeniaNUMANCANNCT03477721
The Role of the Muscle-nervous System Interface in Cancer Cachexia
An observational study of Cachexia; Cancer; Sarcopenia, run by University of Roma La Sapienza at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cachexia; Cancer; Sarcopenia
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 16 Mar 2018to 30 Apr 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- Adult, Older adult
Study population: Oure sample will be selected between cancer patient of Rome Umberto I Hospital
Who may be able to join
- cancer diagnosis
Who cannot join
- continuously use of anti-inflammatory medications;
- present renal and/or liver failure,
- AIDS,
- inflammatory bowel disease or chronic inflammatory processes not related to cachexia.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Department of Clinical Medicine, Sapienza University of Rome
Rome, 00185
Alessandro Laviano, MD, +390649973902, alessandro.laviano@uniroma1.it
About this study
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.
Read the detailed description
The agrin is a protein that acts on neuromuscular junctions (NMJs) promoting stabilization of same, which results in the maintenance and growth of muscle fibers, but the cleavage of agrin, a process by which is formed the agrin fragment C-terminus (CAF), has been linked to the development of sarcopenia, because its presence is directly linked to the reduction in the number of muscle fibers, increasing the heterogeneity of fiber size, presence of Central cores and increasing the proportion of type I fibers and consequently a greater degradation of lean body mass. Studies in mice show that the greatest cleavage of agrin carries on development of sarcopenia and human studies report that individuals with higher serum levels of sarcopenia CAF compared to individuals without sarcopenia.
Therefore, aiming at the complexity of cancer associated with the cachexia and the great importance of the maintenance of lean body mass to a better prognosis in disease, is of fundamental importance to elucidate the role of CAF and the factors associated with sarcopenia, the possible use of these proteins for diagnosis and the contribution that this clarification could bring in clinical therapy.
- Conditions
- Cachexia; Cancer; Sarcopenia
- Keywords
- Agrin Fragment C-terminus (CAF)
- Medical subject headings
- Cachexia, Neoplasms, Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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) | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2018
- Study start16 Mar 2018
- Primary completion16 Apr 2018 (estimated)
- Study completion30 Apr 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Cachexia; Cancer; SarcopeniaStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessandro Laviano, University of Roma La Sapienza
- Investigators
- Alessandro Laviano, MD, Principal investigator, Department of Clinical Medicine, Sapienza University of Rome, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03477721
- Sponsor's protocol ID
- NUMANCAN
- Acronym
- NUMANCAN
- Status last verified
- Mar 2018
- First submitted
- 11 Mar 2018
- Last updated
- 26 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We are still evaluate a researcher to analyze data collected
Publications
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.
PubMed 9276862Argiles 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.
PubMed 19713854Balkwill 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.
PubMed 11229684Batista 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.
PubMed 22099872Belizario 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.
PubMed 27330885Evans 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.
PubMed 18718696Fan 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.
PubMed 23483479Fearon 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.
PubMed 21296615Fearon KC, Moses AG. Cancer cachexia. Int J Cardiol. 2002 Sep;85(1):73-81. doi: 10.1016/s0167-5273(02)00235-8.
PubMed 12163211Fearon 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.
PubMed 16762946Gonzalez-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.
PubMed 25157231Hettwer 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.
PubMed 22433628Kalinkovich 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.
PubMed 25962896Kern KA, Norton JA. Cancer cachexia. JPEN J Parenter Enteral Nutr. 1988 May-Jun;12(3):286-98. doi: 10.1177/0148607188012003286.
PubMed 3292798Kujawski 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.
PubMed 18776941
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Muscle-nervous System Interface in Cancer Cachexia
- ClinicalTrials.gov ID
- NCT03477721
- Acronym / sponsor ID
- NUMANCAN / NUMANCAN
- Conditions
- Cachexia; Cancer; Sarcopenia
- Keywords
- Agrin Fragment C-terminus (CAF)
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 16 Mar 2018 (actual)
- Primary completion
- 16 Apr 2018 (estimated)
- Study completion
- 30 Apr 2018 (estimated)
- First posted
- 26 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The agrin is a protein that acts on neuromuscular junctions (NMJs) promoting stabilization of same, which results in the maintenance and growth of muscle fibers, but the cleavage of agrin, a process by which is formed the agrin fragment C-terminus (CAF), has been linked to the development of sarcopenia, because its presence is directly linked to the reduction in the number of muscle fibers, increasing the heterogeneity of fiber size, presence of Central cores and increasing the proportion of type I fibers and consequently a greater degradation of lean body mass. Studies in mice show that the greatest cleavage of agrin carries on development of sarcopenia and human studies report that individuals with higher serum levels of sarcopenia CAF compared to individuals without sarcopenia.
Therefore, aiming at the complexity of cancer associated with the cachexia and the great importance of the maintenance of lean body mass to a better prognosis in disease, is of fundamental importance to elucidate the role of CAF and the factors associated with sarcopenia, the possible use of these proteins for diagnosis and the contribution that this clarification could bring in clinical therapy.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) | – | – |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Oure sample will be selected between cancer patient of Rome Umberto I Hospital
Key inclusion criteria (1 listed)
- cancer diagnosis
Key exclusion criteria (4 listed)
- continuously use of anti-inflammatory medications;
- present renal and/or liver failure,
- AIDS,
- inflammatory bowel disease or chronic inflammatory processes not related to cachexia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Agrin fragment c-terminus CAF in cancer and cancer cachexia
Time frame: 1 month
To measure the contents of agrin fragment c-terminus (CAF) in plasma of patient with cancer and cancer cachexia.
Agrin fragment c-terminus CAF in cancer sarcopenia
Time frame: 1 month
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.
Agrin fragment c-terminus CAF and IL-6 levels
Time frame: 1 month
To correlate levels of agrin fragment c-terminus (CAF) and IL-6 plasma levels in patients with cancer and with cancer cachexia.
Agrin fragment c-terminus (CAF) and IL-6 and lean body mass
Time frame: 1 month
To correlate levels of agrin fragment c-terminus (CAF) and IL-6 with the lean body mass
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2018.
- Background: PubMed 9276862Argiles 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.
- Background: PubMed 19713854Argiles 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.
- Background: PubMed 11229684Balkwill 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.
- Background: PubMed 22099872Batista 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.
- Background: PubMed 27330885Belizario 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.
- Background: PubMed 18718696Evans 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.
- Background: PubMed 23483479Fan 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.
- Background: PubMed 21296615Fearon 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.
- Background: PubMed 12163211Fearon KC, Moses AG. Cancer cachexia. Int J Cardiol. 2002 Sep;85(1):73-81. doi: 10.1016/s0167-5273(02)00235-8.
- Background: PubMed 16762946Fearon 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.
- Background: PubMed 25157231Gonzalez-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.
- Background: PubMed 22433628Hettwer 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.
- Individual participant dataSharing planned: Undecided. We are still evaluate a researcher to analyze data collected
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessandro Laviano, MD principal investigator
Department of Clinical Medicine, Sapienza University of Rome, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cachexia; Cancer; Sarcopenia, run by University of Roma La Sapienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laviano Alessandro (+390649973902, alessandro.laviano@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Agrin fragment c-terminus CAF in cancer and cancer cachexia (time frame: 1 month). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03477721, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2018.