Longitudinal Neuromuscular and Metabolic Changes With Aging

NCT06168591 | Unknown

• 1 other identifier: UPavia-TrajectorAGE
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Ageing is characterized by a decline in neuromuscular control and a progressive loss of muscle mass, strength and power, leading to reduced mobility, loss of independence, higher hospitalizations rate, and increased all-cause mortality. Several studies suggest a non-linear decay of these age-related changes. Denervation-reinnervation processes, resulting in fewer but larger surviving motor units in advanced age, start as early as age 50-60yr and can be magnified in older adults (\>75yr). Significant functional consequences in daily living activities are not usually observed until approximately 50yr. However, after 50yr, muscle strength/power reduction is accelerated and becomes faster than average muscle mass loss. Most observations come from cross- sectional studies and several confounding factors associated with secondary aging, such as physical activity levels, may contribute to (or compensate for) the observed age-related reductions in neuromuscular function. Compared to cross-sectional designs, prospective ones are advantageous in their ability to investigate fundamental mechanisms by excluding inter-subjects variability. In this project, the investigators will characterize longitudinal age-related changes in motor function, physical performance and muscle aerobic metabolism with an integrated approach. The investigators aim to combine classical methods of in-vivo and ex-vivo evaluation of neuromuscular function with innovative approaches for assessing changes and interactions between neural, structural and metabolic variables in two critical phases of ageing: 55-60yrs and 75-80yrs. Within each age-group, subjects will be classified based on their functional capabilities and divided in either active or sedentary. The investigators will describe the 2-yr time course of 1) mechanisms impairing neuromuscular function (denervation-reinnervation processes); 2) interactions between muscle structural changes and neural/metabolic impairments; 3) functional and metabolic changes occurring at whole muscle as well as single fibers level. The results will extend current understanding of physiological determinants of neuromuscular alterations in aging by identifying the course and rate of changes of specific factors that mediate functional loss and disability in older adults.

Conditions

Aging; Muscle Physiology; Neurophysiology; Exercise Training; Sports Medicine

Outcome Measures

Primary Outcomes (5)

• Perceived quality of life by EQ-5D-5L

  The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/ depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.

  up to 24 months

• Muscle weakness Muscle strength

  Muscle force production during isometric contraction

  up to 24 months

• Exercise tolerance

  Maximal oxygen consumption

  up to 24 months

• Motor unit recruitment

  Neuromuscular adaptations will be assessed using surface EMG detected with grids of electrodes

  up to 24 months

• Muscle Architecture

  Structural adaptations will be assessed in-vivo using Ultrasonography (US)

  up to 24 months

Secondary Outcomes (3)

• Muscle oxidative capacity

  up to 24 months

• Physical activity behavior

  up to 24 months

• Endothelial function

  up to 24 months

Study Arms (1)

ELDERLY

MIDDLE-AGED and OLD individuals of both sexes will be recruited. The stratification into ACTIVE and SEDENTARY will be done according to current public health guidelines

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

MIDDLE-AGED (55-60yrs) and OLD (75-80yrs) individuals of both sexes will be recruited. The stratification into ACTIVE and SEDENTARY will be done according to current public health guidelines and accelerometric data. Participants will be recruited among subjects who routinely visit the facilities of the Clinical Unit of Geriatric for routine evaluations. If inclusion and exclusion criteria are matched, the level of physical activity will be monitored across 7 consecutive days by accelerometers and participants classified as SEDENTARY or ACTIVE.

You may qualify if:

• Community dwelling, mobility and cognitively unimpaired participants will be enrolled. Cognitive assessment: Mini Mental Status Examination (MMSE, cutoff: 24). Physical performance assessments: gait speed over 4-m (WS, \>0,8 m/s), Short Physical Performance Battery (SPPB, \>9), the Timed-Up and Go test (TUG \<20) and grip strength (GRIP, \>27 kg (M) or \>16 kg (F)).

You may not qualify if:

• Parkinson's disease or other neurological disorder; diabetes; stroke; late-stage cancer; chronic kidney disease (IV and V stages); severe liver insufficiency; severe cardiac disorder and major recent heart surgery; severe osteoarthritis.

Sponsors & Collaborators

• University of Pavia: lead
• University of Padova: collaborator
• Politecnico di Milano: collaborator
• Turin, Italy: collaborator
• University of Parma: collaborator

Study Sites (1)

University of Pavia

Pavia, Lombardy, 27100, Italy

RECRUITING

Study Officials

• Fulvio Lauretani, MD

  University of Parma

  STUDY DIRECTOR

Central Study Contacts

Simone Porcelli, MD, PhD

CONTACT

+3903289875; simone.porcelli@unipv.it

Andrea Pilotto, PhD

CONTACT

+3903289875; andrea.pilotto@unipv.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 13, 2023
• Study Start: May 1, 2022
• Primary Completion: November 24, 2023
• Study Completion: May 1, 2025
• Last Updated: December 13, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)