Mitochondria Preservation by Exercise Training: a Targeted Therapy for Cancer and Chemotherapy-induced Cachexia

NCT05028192 | Unknown

• 1 other identifier: N. 98/2021
• Study Type: observational
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to define the contribution of cancer and chemotherapy to muscle and systemic alterations that drive the onset of cachexia in rectal cancer patients and validate in human cancer cachexia (CC) the alterations in mitochondrial function and neuromuscular junction (NMJ) observed in the experimental models, thus providing the rationale for potential anti-cachexia strategies based on exercise and or exercise mimetics.

Conditions

Cachexia; Rectal Cancer

Outcome Measures

Primary Outcomes (18)

• Physical function

  Determinate by the short physical performance battery (SPPB) Score, a series of tests used to evaluate lower extremity function and mobility in older people. Scores are assigned according to performance, with an overall maximum score of 12. A cut off score \< 10 indicates mobility disability and cut point: ≤ 8 points for diagnosing of severe sarcopenia

  Preoperative.

• Physical activity-Subjective Measurement

  Determinate by the physical activity scale for the elderly (PASE) Score, the overall score ranging from 0 to 793, higher scores indicated greater physical activity

  Preoperative

• Physical activity-Objective Measurement (step count)

  Determinate by the average daily step count (total number of steps/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.

  Preoperative.

• Physical activity-Objective Measurement (sleep)

  Determinate by the average of daily sleep duration(total minutes of sleep/ 14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.

  Preoperative.

• Physical activity-Objective Measurement (sedentary time)

  Determinate by the average daily sedentary time (total minutes of inactivity/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.

  Preoperative.

• Physical activity-Objective Measurement (active time)

  Determinate by the average daily active time (total duration of activity in minutes/14 days) recorded by wearing a Smart Watch for two weeks on consecutive days.

  Preoperative.

• Muscular quantity

  Determinate by the Skeletal muscle index (SMI) = skeletal muscle area or cross-sectional area at L4-L5 (cm2)/height2(m2) from the preoperative magnetic resonance imaging.

  Preoperative.

• Muscular quality (muscle fat content) by magnetic resonance imaging

  Determinate by the proton density fat fraction (PDFF) of paraspinal muscles at L4-L5

  Preoperative.

• Nutritional status - Albumin

  Blood levels of albumin (g/dL).

  Preoperative.

• Nutritional status - Prealbumin

  Blood levels of prealbumin(mg/dL).

  Preoperative.

• Nutritional status - transferrin

  Blood levels of transferrin(mg/dL).

  Preoperative.

• General health marker- hemoglobin

  Blood levels of Hemoglobin (g/L).

  Preoperative.

• Inflammatory status-White blood cells count

  White blood cells count (10\^/L).

  Preoperative.

• Inflammatory status - C-reactive protein

  Blood levels of C-reactive protein (mg/dL).

  Preoperative.

• Muscle wasting- creatine kinase

  Blood levels of creatine kinase (U/L).

  Preoperative.

• Morphometric analysis of skeletal muscle

  Description of the dimension and type of muscular fibers from an abdominal wall muscle biopsy harvested intraoperatively.

  within 30 postoperative days.

• Molecular analysis of skeletal muscle

  Characterization of molecular signatures associated with Neo-adjuvant Chemotherapy and rectal cancer by comparing molecular profiles of a muscular biopsies harvested intraoperatively.

  within 60 postoperative days.

• Muscle protein metabolism

  Muscle-specific ubiquitin-ligases expression, mitophagy cargo shuttle, fusion-fission machinery, and mitochondrial biogenesis will be assayed from a muscular biopsy harvested intraoperatively.

  within 60 postoperative days.

Secondary Outcomes (1)

• Overall survival

  3 years after surgery.

Study Arms (2)

Rectal cancer after neoadjuvant treatment

Rectal cancer patients, ycTNM stage II, III, and IV (AJCC 8th), clinically stratified in the pre-cachectic or cachectic stage according to Fearon K et al. definition. That will be subject to curative intent resection or palliative surgery through any approach (open, laparoscopic, or robotic).

Other: no intervention

Control group

Patients who will undergo programmed abdominal surgery through any approach type for no neoplastic or inflammatory disease.

Other: no intervention

Interventions

no intervention OTHER

no intervention

Control group; Rectal cancer after neoadjuvant treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients from all participating centers older than 18 years, males or females, with the primary diagnosis of rectal cancer ycTNM stage II, III or IV (American Joint Committee on Cancer 8th edition), who undergone neoadjuvant therapy. Clinically stratified in the pre-cachectic or cachectic stage according to Fearon K et al. definition. That will be subject to low or ultralow anterior resection, abdominoperineal resection or palliative surgery through any approach (open, laparoscopic or robotic).

You may qualify if:

• Patients with confirmed histopathological diagnosis of rectal adenocarcinoma ycTNM stage II, III, or IV (AJCC 8th).
• Patients treated with neoadjuvant therapy.
• Patients that will be subject to curative intent or palliative surgery through any approach (open, laparoscopic, or robotic).
• Ability to sign the informed consent.

You may not qualify if:

• Rectal cancer stage I or any stage without neoadjuvant therapy.
• Age \< 18 and \>75 years
• Long steroid treatment for any cause.
• Emergency setting.
• Co-existent inflammatory bowel disease.
• Inflammatory comorbidities (liver failure, diabetes, metabolic acidosis, acute and chronic renal failure, sepsis, AIDS, acute and chronic hepatitis, autoimmune disorders, and chronic obstructive pulmonary disease).
• Healthy volunteers.
• Other (simultaneous) neoplastic disease

Sponsors & Collaborators

• University of Turin, Italy: lead
• University of Padova: collaborator
• Catholic University of the Sacred Heart: collaborator
• University of Roma La Sapienza: collaborator

Study Sites (1)

Ospedale San Luigi Gonzaga

Orbassano, Turin, 10043, Italy

Location

Related Publications (8)

• Dev R. Measuring cachexia-diagnostic criteria. Ann Palliat Med. 2019 Jan;8(1):24-32. doi: 10.21037/apm.2018.08.07. Epub 2018 Sep 7.

  PMID: 30525765 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

• Freire PP, Fernandez GJ, Cury SS, de Moraes D, Oliveira JS, de Oliveira G, Dal-Pai-Silva M, Dos Reis PP, Carvalho RF. The Pathway to Cancer Cachexia: MicroRNA-Regulated Networks in Muscle Wasting Based on Integrative Meta-Analysis. Int J Mol Sci. 2019 Apr 22;20(8):1962. doi: 10.3390/ijms20081962.

  PMID: 31013615 BACKGROUND

• Baracos VE. Skeletal muscle anabolism in patients with advanced cancer. Lancet Oncol. 2015 Jan;16(1):13-4. doi: 10.1016/S1470-2045(14)71185-4. Epub 2014 Dec 16. No abstract available.

  PMID: 25524803 BACKGROUND

• Wiegert EVM, de Oliveira LC, Calixto-Lima L, Borges NA, Rodrigues J, da Mota E Silva Lopes MS, Peres WAF. Association between low muscle mass and survival in incurable cancer patients: A systematic review. Nutrition. 2020 Apr;72:110695. doi: 10.1016/j.nut.2019.110695. Epub 2019 Dec 7.

  PMID: 32007806 BACKGROUND

• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jul 1;48(4):601. doi: 10.1093/ageing/afz046. No abstract available.

  PMID: 31081853 BACKGROUND

• Penet MF, Bhujwalla ZM. Cancer cachexia, recent advances, and future directions. Cancer J. 2015 Mar-Apr;21(2):117-22. doi: 10.1097/PPO.0000000000000100.

  PMID: 25815852 BACKGROUND

• Codari M, Zanardo M, di Sabato ME, Nocerino E, Messina C, Sconfienza LM, Sardanelli F. MRI-Derived Biomarkers Related to Sarcopenia: A Systematic Review. J Magn Reson Imaging. 2020 Apr;51(4):1117-1127. doi: 10.1002/jmri.26931. Epub 2019 Sep 13.

  PMID: 31515891 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Oblique or rectus abdominis muscle biopsy.

MeSH Terms

Conditions

Cachexia; Rectal Neoplasms

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Maurizio Degiuli, Prof.

  Università degli studi di Torino- Surgical Oncology and Digestive Surgery

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: August 31, 2021
• Study Start: September 27, 2021
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: September 29, 2021

Record last verified: 2021-09

Locations

IT (1)