AgingTrajectorAGENCT06168591
Longitudinal Neuromuscular and Metabolic Changes With Aging
An observational study of Aging and Muscle Physiology, run by University of Pavia at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 80 years
- Conditions the study is for
- Aging, Muscle Physiology, Neurophysiology
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- 1 May 2022to 1 May 2025
- 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 55 to 80 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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)).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
University of Pavia
Pavia, Lombardy, 27100
Simone Porcelli, MD, PhD, +3903829875 ext. 38, simone.porcelli@unipv.it
About this study
Official title: Neuromuscular Impairment in Aging: a Longitudinal Study of Structural and Functional Mechanistic Bases of Age-related Alterations
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.
Read the detailed description
State of the art The life expectancy of humans has continuously increased in most countries over the last century. With extended life expectancy, quality of life of elderly is a priority. However, ageing is a physiological process characterized by a decline in neuromuscular control and a progressive loss of muscle mass, strength and power. These impairments negatively affect mobility, increase morbidity and have dramatic individual and societal impacts.
On average, elderly walk more slowly, have less muscle strength and power, have poorer memory and reasoning abilities, and are slower to respond on speeded cognitive tasks relative to younger adults. In cross-sectional reports age-related changes in physical capability and associations between lower physical capability levels and higher mortality rates are consistently found. Nevertheless, there is a growing body of literature suggesting that chronological age alone cannot account for the heterogeneity in structural, functional, and physiological changes associated with human ageing.
One of the main neurophysiological mechanisms underlying the age-related changes in muscle function is the progressive loss of motor neurons, usually accompanied by instability of NMJ. The extent to which this phenomenon affects muscle structure, neuromuscular control and their interaction at different ageing phases is only partly described, also due to the wide inter-subject variability.
Moreover, in aged adults slower gait speed, lower muscle strength and changes in muscle quality have been correlated to impaired skeletal muscle oxidative capacity, with elderly showing lower O2 consumption at peak exercise and impaired submaximal muscle oxidative function compared to young.
The literature reports are mainly cross-sectional and factors associated with secondary aging such as physical activity levels may influence cross-sectional data. Thus, a longitudinal monitoring of neuromuscular and metabolic impairments in aging is needed, aiming to:
AIM 1 - Describe longitudinal age-related changes in motor function and physical performance with combined muscle mass and muscle aerobic metabolism AIM 2 - Identify the underlying mechanisms impairing in-vivo neuromuscular function by changes in muscle denervation and reinnervation AIM 3 - Define the role of skeletal muscle structural remodeling and muscle bioenergetics decline at whole-body level on neuromuscular impairments AIM 4 - Quantify functional and metabolic changes occurring at single muscle fibers level AIM 5 - Determine level of physical activity and related beneficial effects
- Conditions
- Aging, Muscle Physiology, Neurophysiology, Exercise Training, Sports Medicine
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 |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 24 months
Muscle weakness Muscle strength
Muscle force production during isometric contraction
Measured: up to 24 months
Exercise tolerance
Maximal oxygen consumption
Measured: up to 24 months
Motor unit recruitment
Neuromuscular adaptations will be assessed using surface EMG detected with grids of electrodes
Measured: up to 24 months
Muscle Architecture
Structural adaptations will be assessed in-vivo using Ultrasonography (US)
Measured: up to 24 months
Secondary outcomes (3)
Muscle oxidative capacity
Mitochondrial function will be estimated in vivo by near infrared spectroscopy
Measured: up to 24 months
Physical activity behavior
Levels of physical activity will be monitor by accelerometric wearable devices
Measured: up to 24 months
Endothelial function
Blood flow changes during leg passive movement will be recorded by ultrasound
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2023
- Study start1 May 2022
- Primary completion24 Nov 2023
- Study completion1 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pavia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Padova, Politecnico di Milano, Turin, Italy, University of Parma
- Responsible party
- Principal investigator, Simone Porcelli, University of Pavia
- Investigators
- Fulvio Lauretani, MD, Study director, University of Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06168591
- Sponsor's protocol ID
- UPavia-TrajectorAGE
- Acronym
- TrajectorAGE
- Status last verified
- Dec 2023
- First submitted
- 24 Nov 2023
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuromuscular Impairment in Aging: a Longitudinal Study of Structural and Functional Mechanistic Bases of Age-related Alterations
- ClinicalTrials.gov ID
- NCT06168591
- Acronym / sponsor ID
- TrajectorAGE / UPavia-TrajectorAGE
- Conditions
- Aging, Muscle Physiology, Neurophysiology, Exercise Training, Sports Medicine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of PaviaUniversity, hospital or other
- Collaborators
- University of Padova, Politecnico di Milano, Turin, Italy, University of Parma
- Study start
- 1 May 2022 (actual)
- Primary completion
- 24 Nov 2023 (actual)
- Study completion
- 1 May 2025 (estimated)
- First posted
- 13 Dec 2023 (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.
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.
Detailed description
State of the art The life expectancy of humans has continuously increased in most countries over the last century. With extended life expectancy, quality of life of elderly is a priority. However, ageing is a physiological process characterized by a decline in neuromuscular control and a progressive loss of muscle mass, strength and power. These impairments negatively affect mobility, increase morbidity and have dramatic individual and societal impacts.
On average, elderly walk more slowly, have less muscle strength and power, have poorer memory and reasoning abilities, and are slower to respond on speeded cognitive tasks relative to younger adults. In cross-sectional reports age-related changes in physical capability and associations between lower physical capability levels and higher mortality rates are consistently found. Nevertheless, there is a growing body of literature suggesting that chronological age alone cannot account for the heterogeneity in structural, functional, and physiological changes associated with human ageing.
One of the main neurophysiological mechanisms underlying the age-related changes in muscle function is the progressive loss of motor neurons, usually accompanied by instability of NMJ. The extent to which this phenomenon affects muscle structure, neuromuscular control and their interaction at different ageing phases is only partly described, also due to the wide inter-subject variability.
Moreover, in aged adults slower gait speed, lower muscle strength and changes in muscle quality have been correlated to impaired skeletal muscle oxidative capacity, with elderly showing lower O2 consumption at peak exercise and impaired submaximal muscle oxidative function compared to young.
The literature reports are mainly cross-sectional and factors associated with secondary aging such as physical activity levels may influence cross-sectional data. Thus, a longitudinal monitoring of neuromuscular and metabolic impairments in aging is needed, aiming to:
AIM 1 - Describe longitudinal age-related changes in motor function and physical performance with combined muscle mass and muscle aerobic metabolism AIM 2 - Identify the underlying mechanisms impairing in-vivo neuromuscular function by changes in muscle denervation and reinnervation AIM 3 - Define the role of skeletal muscle structural remodeling and muscle bioenergetics decline at whole-body level on neuromuscular impairments AIM 4 - Quantify functional and metabolic changes occurring at single muscle fibers level AIM 5 - Determine level of physical activity and related beneficial effects
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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)).
Key exclusion criteria (1 listed)
- 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.
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
Perceived quality of life by EQ-5D-5L
Time frame: up to 24 months
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.
Muscle weakness Muscle strength
Time frame: up to 24 months
Muscle force production during isometric contraction
Exercise tolerance
Time frame: up to 24 months
Maximal oxygen consumption
Motor unit recruitment
Time frame: up to 24 months
Neuromuscular adaptations will be assessed using surface EMG detected with grids of electrodes
Muscle Architecture
Time frame: up to 24 months
Structural adaptations will be assessed in-vivo using Ultrasonography (US)
3 secondary outcomes
Muscle oxidative capacity
Time frame: up to 24 months
Physical activity behavior
Time frame: up to 24 months
Endothelial function
Time frame: up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Individual participant dataSharing planned: No
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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.
Fulvio Lauretani, MD study director
University of Parma
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 Aging and Muscle Physiology, run by University of Pavia 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 1 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 13 Dec 2023. 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 Simone Porcelli, MD, PhD (+3903289875 ext. 38, simone.porcelli@unipv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perceived quality of life by EQ-5D-5L (time frame: up to 24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Dec 2023.