Role of HIF-1α in Skeletal Muscle Aging

NCT03371134 | Unknown DMC

• 1 other identifier: HIF
• Study Type: observational
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

Deficits in skeletal muscle function exist during aging and muscular dystrophy, and suboptimal function has been related to factors such as atrophy, excessive inflammation and fibrosis. Sarcopenia is the age-related loss of skeletal muscle mass and function. It is now recognised as a major clinical problem for older people and research in the area is expanding exponentially. This interest stems from the fact that sarcopenia is both common and associated with serious health consequences in terms of frailty, disability, morbidity and mortality. The age-related loss of human skeletal muscle mass is due to a decrease in myofibre size and number with the loss of both fast and slow type myofibres, although the loss of fast myofibres tends to start earlier, at ∼70 years. Many factors influence the decrease in muscle mass. A significant contributor is an anabolic resistance of older skeletal muscle to protein nutrition as seen during immobilisation which can be ameliorated at least in part by resistance exercise and dietary supplementation. Other intensive areas of research are related to the loss of innervation and oxidative damage. Moreover, ineffective muscle regeneration underlies each condition and has been attributed to a deficit in myogenic potential of resident stem cells or satellite cells. It is now widely accepted that satellite cells, and generally adult stem cells, are normally quiescent and tend to reside in hypoxic areas of the tissue to preserve their undifferentiated state. To govern these processes, cells have developed a very complex machinery that is mainly regulated by a group of transcription factors known as hypoxia-inducible factors (HIFs). In particular, several observations support the idea that oxygen deprivation and HIF-1a may play a key role during ischemia to activate the regeneration process, which, after an initial hypoxic insult, needs to proceed under normoxia. On these bases, in this study we will investigate the role of HIF-1a in skeletal atrophy during aging.

Conditions

Sarcopenia

Outcome Measures

Primary Outcomes (1)

• Evaluation of HIF-1a expression levels in satellite cells isolated from sarcopenic and young

  Western blot analysis of HIF-1a levels and of its downstream targets (Vascular Endothelial Growth Factor: VEGF, phosphoglycerate kinase: PGK, Prolylhydroxilases: PHD2)

  1 year

Secondary Outcomes (6)

• Evaluation of sarcopenic profile in satellite cells harvested from old sarcopenic patients

  6 months

• Correlation of HIF-1a levels with the degree of sarcopenia in the satellite cells of old sarcopenic patients

  1 year

• Evaluation of differences in satellite cells number between young and old patients

  6 months

• Evaluation of HIF-1a stabilization on satellite cells treated with PHDs inhibitors

  1 year

• Evaluation of satellite cell proliferation in cells treated with PHDs inhibitors

  1 year

Study Arms (2)

Sarcopenic group

Harvesting of muscular biopsies Muscular biopsies will be harvested from old sarcopenic patients undergoing hip replacement surgery

Biological: Harvesting of muscular biopsies

Control group

Harvesting of muscular biopsies Muscular biopsies will be harvested from young patients undergoing Anterior Cruciate Ligament (ACL) reconstruction surgery

Biological: Harvesting of muscular biopsies

Interventions

Harvesting of muscular biopsies BIOLOGICAL

Muscular biopsies will be harvested during surgery; them satellite cells will be isolated and characterized in vitro.

Control group; Sarcopenic group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be selected and evaluated in the primary care clinic. The eligibility criteria will be checked 2-4 weeks before surgery. Muscular biopsies will be harvested from discarded material during surgery.

You may qualify if:

• Sarcopenic patients (measured by DXA) affected by hip osteoarthritis, developmental dysplasia of the hip or hip fracture and undergoing hip replacement surgery (for the sarcopenic group)
• Patients affected by traumatic ACL tears and undergoing ACL reconstruction surgery (for the control group)
• Patients between 18 and 35 years old (for the control group)
• Patients between 65 and 90 years old (for the sarcopenic group)
• ≤ Body Mass Index (BMI) ≤ 30 kg/m2

You may not qualify if:

• Diseases that can affect bone or muscle metabolism
• Pharmacological therapies that can interact with bone or muscle metabolism
• Bone metastases
• Bone infections
• HIV, hepatitis B virus, hepatitis C virus or Treponema pallidum positivity
• BMI ≥30kg/m2

Sponsors & Collaborators

• I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio: lead

Biospecimen

Retention: SAMPLES WITH DNA

Satellite cells isolated from muscular biopses

MeSH Terms

Conditions

Sarcopenia

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Laura Mangiavini, Dr

  IRCCS Istituto Ortopedico Galeazzi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Mangiavini, Dr

CONTACT

00390266214930; laura.mangiavini@grupposandonato.it

Study Design

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

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 13, 2017
• Study Start: January 10, 2018
• Primary Completion: January 10, 2019
• Study Completion: July 26, 2020
• Last Updated: December 14, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share