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NCT Number: NCT07678736

The Muscle Monitor: Early Skeletal Muscle Indicators of Insulin Resistance and Cardiometabolic Risk

Insulin resistance is an early etiological factor in the development of type-2 diabetes (T2D), which constitutes a large societal health burden with an expected additional rise in the years to come.

Skeletal muscle is the body's largest lean tissue mass and the major site of glucose disposal in response to insulin stimulation. Prior studies have suggested that a fast skeletal muscle phenotype, including a predominant fast muscle fiber composition, reduced capillary density, low fat oxidation and muscle oxidative capacity may be implicated in insulin resistance and TD2 development. However, key questions pertain in relation to the cause and effect of these relationships as well as the interaction with potential confounders and effect-modifiers including life-style factors (e.g. diet and physical activity levels) and general participant characteristics (e.g. body composition and training status).

In the present project, we therefore aim to derive muscle fiber type and extensively map the proteomic signature of the early stages of insulin resistance in a large cross-sectional study using a young and apparently healthy cohort prior to T2D development, including a thorough participant characterization. We will recruit ~250 participants (men and women) in the age of 20-30 years and conduct extensive phenotyping and tissue sampling across one laboratory-based test day and a scan visit, as well as measurements of physical activity level and glucose handling in free-living conditions with wearable sensors.

The study has a longitudinal aspect as participants will be re-invited at 5-year intervals for up to 20 years to delineate the trajectory of metabolic health in relation to muscle phenotype measures.

The results of the project are expected to lead to significant advancements in our understanding of the importance of muscle phenotype for early-stage insulin resistance and metabolic health trajectories. Such understanding has potentially important clinical implications, as it can open new avenues for targeted interventions and individualized early preventive strategies to counter or delay the progression of insulin resistance and associated metabolic and cardiovascular disorders.

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Key information

Age range

20 year–30 year

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

The project is composed of 1) a screening visit to determine study eligibility, 2) a main test day in the lab, 3) 10 days of physical activity tracking and continuous glucose monitoring in free-living conditions and 4) a scan visit including a whole-body MRI scan and lower leg pQCT scan.

For the main lab visit the participants will arrive in the morning after an overnight fast. This visit includes measurements of anthropometrics, resting metabolic rate, resting heart rate + heart rate variability, arterial stiffness, intima media thickness, as well as blood pressure obtained in the supine position. In addition, a fasting blood sample will be obtained followed by a 2-h glucose tolerance test with concomitant questionnaires provided in writing on basic demographics, physical activity level, sleep, stress and mental health. Two thigh muscle biopsies and a subcutaneous adipose tissue fat sample from the abdominal region will be obtained, while maximal voluntary knee-extensor contraction torque and rate of force development will be measured. Lastly, cycling-based assessments of maximal fat oxidation rate, peak power and maximal oxygen uptake will be assessed using indirect calorimetry including capillary lactate samples.

The scan visit will consist of an MRI whole-body scan, soleus and gastrocnemius 1H-MRS and a pQCT bone scan of the lower limb at 4% and 66% of the total bone length.

The objective measurements of physical activity levels and glucose-handling capacity will be performed for 10 days in free-living conditions using feasibly worn sensors (continuous glucose monitor and thigh-worn accelerometer). During this time, a food dairy needs to be filled in during two week days and one weekend day to estimate the habitual food intake.

A standardized evening meal will be provided prior to the laboratory-based test day and a standardized lunch meal served during the testing day.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Sex: Males and females
  • Age: 20-30 years
  • BMI <35
  • Healthy (no diagnosed chronic disease)

Exclusion criteria

  • Chronic disease deemed to affect study outcomes
  • Disease that increase haemorrhage risk
  • Daily intake of medication that could confound study outcomes
  • Regular smokers
  • Active pregnancy
  • Immobilization (inactivity due to injury or illness, e.g. cast or brace) for more than a week in the month prior to the study or for more than 4 weeks in the past 6 months prior to the study
  • Very high structured physical exercise level (>10 h/week).
  • Participants not willing to adhere to standardized meal prescriptions included in the study protocols will also be excluded (due to e.g. allergies or specific dietary preferences)

Treatment and study plan

Primary outcomes

  1. Whole-body insulin sensitivity

    Time frame: At baseline and at 5-year intervals for up to 20 years

    The Matsuda index derived from an oral glucose tolerance test

Secondary outcomes

  1. Skeletal muscle fiber type

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Skeletal muscle fiber type assessed using SDS page

  2. Molecular skeletal muscle profile

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Molecular profiling of skeletal muscle tissue, including proteomic and related pathway-level analyses relevant to metabolic function.

  3. MRI-derived muscle and fat volumes

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Whole-body MRI-derived muscle and fat volumes at the total and regional body level

  4. MRI derived tissue fat infiltration

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Whole-body MRI-derived tissue fat infiltration in the liver, intermuscular and intramuscular area

  5. Physical activity level

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Accelerometer-based physical activity levels

  6. HOMA-IR

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Homeostatic Model Assessment of Insulin Resistance based on fasted blood sampling

  7. Cardiorespiratory fitness

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Maximal oxygen uptake assessed using indirect calorimetry during incremental cycling

  8. Muscle strength

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Maximal voluntary isometric contraction torque assessed in a dynamometer

  9. Free-living glycaemic control

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Continuous glucose monitoring-derived glycaemic metrics during free-living conditions

  10. Dietary intake

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Dietary intake assessed using repeated 24-hour food diaries and food frequency questionnaires, including estimates of energy intake and macronutrient composition.

  11. Subcutaneous adipose tissue phenotyping

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Proteomics derived measures of adipose tissue phenotype

  12. Maximal fat oxidation rate

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Maximal fat oxidation rate obtained using indirect calorimetry during incremental cycling

  13. Pulsewave velocity

    Time frame: At baseline and at 5-years intervals for up to 20 years

    Carotid-femoral pulsewave velocity measured using Doppler echocardiography with ECG gating

  14. Resting heart rate

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Resting heart rate assessed using a chest-worn heart rate monitor

  15. Heart rate variability

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Heart rate variability assessed using a chest-worn heart rate monitor

Other outcomes

  1. Blood pressure

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Systolic and diastolic blood pressure obtained using a sphygmomanometer

  2. 10 s sprint peak and average power

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Peak and average power output during a 10 s sprint test

  3. Lactate accumulation

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Lactate accumulation during a 10 s cycling sprint test

  4. Blood lipid profile

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Including measures of triglycerides, free fatty acids, lipoprotein (a), cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol

  5. Bone measurements

    Time frame: At baseline and at 5-year intervals for up to 20 years

    Bone density assessed using peripheral quantitative computed tomography (pQCT).

Study contacts

Contact information is provided by the study sponsor or research team.

Eline Lievens, Professor

CONTACT

[email protected]

00320478312585

Jeppe Foged Vigh-Larsen, PhD

CONTACT

[email protected]

004529870635

Sponsors and collaborators

Lead sponsor

University Ghent

Other

Collaborators

  • University Hospital, Ghent

Registry information

Official study title

The Muscle Phenotype and Cardiometabolic Health Monitoring Project

Acronym: MUSCLE MONITOR

Important dates

Study start
2025
Primary completion
2046
Study completion
2046
First posted
Jul 1, 2026
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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