Concurrent Assessment of Skeletal Muscle Mass and Synthesis/Breakdown in Old Age

Concurrent Assessment of Skeletal Muscle Mass and Synthesis/Breakdown in Old Age: Defining Diagnostics and the Aetiology of Sarcopenia to Identify "At-risk" Individuals and Appropriate Countermeasures

This study involves minimally-invasive techniques to measure muscle mass, muscle protein breakdown and synthesis simultaneously in older age.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Muscle Atrophy
• Intervention / Treatment: Other: D3-Creatine; Other: Deuterium Oxide; Other: D3-3-methylhistidine

Detailed Description

Most people will have noticed that with age people become frail. This is principally due to wasting of skeletal muscle known as "sarcopenia". Crucially, sarcopenia is more than just a symptom of weakness and poor functional capacity; it exposes people to an increased risk of falls and fractures, impacting quality of life, independence, health status and ultimately lifespan. Muscles represent the largest organ in the body, making up over 50% of total body weight. Most people know that skeletal muscles are important for movement and to support the skeleton, but not everyone is aware of how important muscles are for whole-body health. For example, muscles represent a vast protein store containing amino acids (the building blocks of protein) which can be broken down in times of fasting, infection and disease in order to provide energy to help other vital organs. Because of the detrimental effects on health, and the associated health costs, sarcopenia is of grave concern. Therefore, there is a significant clinical need to pre-identify at-risk older individuals who have low muscle mass so that they can be offered an intervention (of diet, exercise or drug-based) before they suffer any of the potential problems outlined above. Current techniques for measuring whole-body muscle mass, including MRI and CT are time-consuming, expensive and in huge demand in hospital settings, meaning that muscle wasting conditions such as sarcopenia often go undiagnosed. In this project we propose a potential solution to this problem by developing a diagnostic of sarcopenia that requires only a single drink and subsequent urine collection. In addition, throughout this project we aim to explore the mechanisms underlying muscle wasting by assessing the muscle of those with low and 'normal' muscle mass.

• Study Type: Observational
• Enrollment (Actual): 37

Contacts and Locations

Study Locations

• United Kingdom
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3DT
      • Royal Derby Hospital Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Generally healthy older adults

Description

Inclusion Criteria:

- Healthy volunteers of normal body mass index (BMI <35 kg/m2), aged 65-85 years

Exclusion Criteria:

• A BMI > 35 kg/m2

• Active cardiovascular disease:

  o angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event

• Cerebrovascular disease:

  o previous stroke, aneurysm (large vessel or intracranial), epilepsy

• Respiratory disease including:

  o pulmonary hypertension, COPD

• Metabolic disease:

  o hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, type 1 or 2 diabetes

• Active inflammatory bowel or renal disease
• Malignancy
• Recent steroid treatment (within 6 months) or hormone replacement therapy
• Clotting dysfunction

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of D3-Creatine in Urine: 24 hours	To use 30mg of D3-Creatine to measure muscle creatine pool size (g) and whole-body muscle mass (kg) from urine samples taken between 0 and 72 hours. The 0-24 hours collection provides a measure of creatine spillover.	Up to 24 hours
Measurement of muscle mass using D3-Creatine: 48 hours	To use 30mg of D3-Creatine to measure muscle creatine pool size (g) and whole-body muscle mass (kg) from urine samples taken between 0 and 72 hours. The 0-24 hours collection provides a measure of creatine spillover, spot urines at 48 and 72 hours provide a measurement of the dilution of tracer in urinary creatinine and thus the total muscle creatine pool size.	48 hours
Measurement of muscle mass using D3-Creatine: 72 hours	To use 30mg of D3-Creatine to measure muscle creatine pool size (g) and whole-body muscle mass (kg) from urine samples taken between 0 and 72 hours. The 0-24 hours collection provides a measure of creatine spillover, spot urines at 48 and 72 hours provide a measurement of the dilution of tracer in urinary creatinine and thus the total muscle creatine pool size.	72 hours
Rate of dilution of D3-3MH by endogenous unlabelled 3MH release in blood	Using 10mg of D3-3-methylhistidine (D3-3MH) and subsequent multiple blood sampling between 24 and 30h, the rate of dilution of D3-3MH by endogenous unlabelled 3MH release provides a measure of the rate of whole-body muscle protein breakdown.	6 hours (from 24 through to 30 hours)
Rates of Muscle Protein Synthesis	Using D2O, rate of muscle protein synthesis will be calculated, cumulatively, over 0-3 days by measuring deuterium labelling of alanine into protein from a muscle biopsy at 72 hours.	3 days

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Abbeyfield

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 7, 2016
• Primary Completion (ACTUAL): January 31, 2020
• Study Completion (ACTUAL): February 1, 2020

Study Registration Dates

• First Submitted: February 5, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (ACTUAL): October 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Sarcopenia; Muscular Atrophy; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Radiation-Protective Agents; Deuterium Oxide
• Other Study ID Numbers: Abbeyfield

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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