Identification of Relevant Biological, Imaging, Mobility and Clinical Markers for Clinical Research in Sarcopenia

The objective of this trial is to constitute a cohort of sarcopenic versus non-sarcopenic patients to validate the most relevant biological, imaging, mobility and clinical markers considered individually or in association for the diagnosis of sarcopenic patients.

Study Overview

• Status: Recruiting
• Conditions: Sarcopenia
• Intervention / Treatment: Procedure: Biopsy

Detailed Description

This trial is part of a Research Program partly funded by a grant from the Walloon region entitled "Development of Markers of Sarcopenia Using an Integrated Approach : From Cell to Human".

Consistent with the above-mentioned observation, there is not only one biological marker that perfectly matches the sarcopenia criteria but there is a range of complementary biomarkers - including but not limited to inflammation markers, products of oxidative damage, serum creatinine and urinary creatinine excretion, endocrine function, urine proteomics panel, N-terminal procollagen peptides, myostatin and agrin fragment - that will together constitute the ideal panel of markers (Fougère et al, 2015). These current biomarkers and the thresholds for correlation with clinical outcomes have to be deeply evaluated in clinical trials before being considered as good biomarkers.

In addition, one research priority is to investigate and define novel biomarkers allowing an improved assessment, characterization and follow-up of elderly people with sarcopenia. Biomarkers derived from blood can indeed easily be measured in a standardized and low-cost way and are therefore very attractive.

This clinical trial aims at confirming the relevance of new soluble markers and validating the most relevant biological (previously and newly identified), imaging, mobility and clinical markers for clinical research in sarcopenia.

Newly identified soluble markers of sarcopenia coming from DEMAIN Research program and using secretomic approach (to be identified in secretome of human myotubes during the program research) using immunoassays on biological fluids.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yves Henrotin, Prof; Phone Number: 0032 4 242 77 06; Email: yves.henrotin@artialis.com
• Study Contact Backup: Name: Bérénice Coste, PhD; Phone Number: 0032 4 242 77 47; Email: berenice.costes@artialis.com

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • Recruiting
    • Universitair Ziekenhuis Brussel
    • Principal Investigator: Ivan Bautmans, MD, Phd
  • Brussels, Belgium, 1070
    • Recruiting
    • Erasme hospital
    • Principal Investigator: Sandra De Breucker, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants will have the following inclusion criteria:

• Male with age ≥ 65 years
• Body Mass Index: 20 < BMI < 35 kg/m2
• Able to understand and having signed an informed consent
• Able to follow the trial procedures

Sarcopenic population: diagnosed sarcopenia following definition of the EWGSOP2:

• Muscle strength assessed by the handgrip test <27 kg for male
• Skeletal muscle mass index (Appendicular lean muscle mass) assessed by DXA <7.0 kg/m2

Non-sarcopenic population: adapted from the EWGSOP2:

• Muscle strength assessed by the handgrip test ≥ 27 kg
• Skeletal muscle mass index (Appendicular lean muscle mass) assessed by DXA ≥ 7.0 kg/m2

Exclusion Criteria:

Participants will have the following exclusion criteria:

• Any clinically significant levels of the safety parameters (Creatine Kinase (CK), activated Partial Thromboplastin Time (aPTT), Prothrombin Time and International Normalized Ratio (PT/INR))
• Any severe, uncontrolled and limiting diseases (e.g. systemic inflammation, infectious diseases, active cancer, neurodegenerative disorders, diabetes) left to the investigator's discretion
• Bed resting for more than 10 days during the 3 months preceding the recruitment
• Immobilization of the lower limb, lasting more than one week during the 3 months preceding recruitment
• Medical treatment with anticoagulant, insulin, immunosuppressant, long-term corticosteroid (over 7.5 mg prednisone or its equivalent)
• Severe incapacity (class IV Steinbrocker Functional Classification - Appendix 2)
• Any treatment that may affect physical performance, muscle function, disrupts study measures or impairs the understanding of consent
• Known acute or severe renal insufficiency (glomerular filtration rate < 30 mL/min/1.73m2)
• Cushing' syndrome
• Known cachexia
• Currently participating or having participated in another therapeutic clinical trial in the three previous months
• Under guardianship or judicial protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sarcopenic population; Diagnosed sarcopenia following definition of the EWGSOP2: Muscle strength assessed by the handgrip test <27 kg; Skeletal muscle mass index (Appendicular lean muscle mass) assessed by DXA <7.0 kg/m2	Procedure: Biopsy; Muscle biopsy from vastus lateralis (100-200 mg from non-dominant leg)
Active Comparator: Non sarcopenic population; Non-sarcopenic population adapted from the EWGSOP2: Muscle strength assessed by the handgrip test ≥ 27 kg; Skeletal muscle mass index (Appendicular lean muscle mass) assessed by DXA ≥ 7.0 kg/m2	Procedure: Biopsy; Muscle biopsy from vastus lateralis (100-200 mg from non-dominant leg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identified soluble markers of sarcopenia	immunoassays on biological fluids by secretomic approach	3 months after biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identified imaging marker	Appendicular lean muscle mass and adiposity (if possible) using Dual Energy Xray Absorptiometry (DXA)	within 15 days after Day 0 (baseline visit)
Determine thePhysical performance	Patients realize some physical tests: Short Physical Performance Battery (SPPB that are three physical tests: gait speed, balance test, chair stand test)	Day 0 (baseline visit)
Determine the falls risk	A global score will be calculated in function of the answers of a Self-administered questionnaire: Morse Fall Scale (MFS; falls risks for elderly)	Day 0 (baseline visit)
Identified clinical marker	A global score will be calculated in function of the answers of a Self-administered questionnaire: SARC-F	Day 0 (baseline visit)
Determine the muscle strength	Handgrip muscular strength test (upper body skeletal muscle function) using a hand dynamometer	Day 0 (baseline visit)
Evaluate the quality of life	A global score will be calculated in function of the answers of a Self-administered questionnaire (SF-36). The SF-36 is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.	Day 0 (baseline visit)
Determine cognitive performance	A global score will be calculated in function of the answers of a Self-administered questionnaire: Montreal Cognitive Assessment (MoCA)	Day 0 (baseline visit)
Determine the nutrition status	A global score will be calculated in function of the on Global Leadership Initiative on Malnutrition (GLIM) criteria (Cederholm et al, 2018)	Day 0(baseline visit)
Evaluate the tolerance	Number of Adverse events (AE or Adverse Device Effect or Device Deficiency; will be coded in terms of System Organ Class (SOC) and Low Level Terms (LLT) using the last version of MedDRA) and drop offs	3 months (baseline visit to biopsy)

Collaborators and Investigators

• Sponsor: Artialis
• Investigators: Study Director: Yves Henrotin, Prof, Artialis

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: DEMAIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No