Muscle in Obesity: Imaging, Function and microRNA

NCT04300504 | Completed

• 1 other identifier: STH21022
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Growing evidence suggests that dynapenic abdominal obesity is associated with a greater risk of falls, functional disability and hospitalisation compared to those with dynapenia, obesity or neither phenotype. Understanding the pathogenesis underlying this phenotype has the potential to inform potential treatment strategies. MicroRNAs can act as messengers at the cellular level to promote or block processes for muscle growth and repair, amongst other things. There is evidence that ageing changes microRNA levels in the muscle and that these changes may result in reduced muscle quality and quantity. However, it is not known whether being obese can change microRNA levels in muscle and how this relates to physical performance. The aim of this study is to investigate the effect of dynapenic abdominal obesity on microRNA levels in serum and muscle quality and quantity in the legs of older women. This is an observational, cross-sectional study. The investigators will recruit 4 groups of older women: normal weight, normal weight with dynapenia, obese and obese with dynapenia. The investigators will measure the microRNA levels in serum. The investigators will measure the quantity and fat content of muscle in the legs using magnetic resonance imaging. Muscle strength, fatigue and balance will be measured using gait (walking) analysis, balance tests, and a machine designed to measure leg strength and fatigue. The investigators will measure and compare microRNA levels between groups. The investigators will use databases and computer programmes to look at all of the microRNAs which are different between groups and see how they affect the muscle. The investigators will compare muscle strength, size and fatigue between groups. The investigators will explore relationships of muscle quantity and quality measures with microRNA changes in the muscle. This approach will allow the investigators to understand how obesity affects the microRNA profile of muscle and whether this translates into impairment of function and mobility.

Conditions

Muscle Function

Keywords

obesity; sarcopenia; dynapenia; microRNA

Outcome Measures

Primary Outcomes (1)

• Differential microRNA expression, expressed as fold-change and p-values, measured using real time quantitative polymerase chain reaction (RT-qPCR) between normal weight and obese groups, further stratified by dynapenia

  Serum analyses

  1 day (one measurement )

Secondary Outcomes (5)

• mean difference in distance walked during 6 minute walk test between normal weight and obese, further stratified by dynapenia

  1 day (one measurement )

• mean difference in muscle mass and volume measures between normal weight and obese, further stratified by dynapenia MRI

  1 day (one measurement )

• mean difference in muscle mass and volume measures between normal weight and obese, further stratified by dynapenia DXA

  1 day (one measurement )

• mean difference in muscle strength between normal weight and obese, further stratified by dynapenia

  1 day (one measurement )

• mean difference in fatigue between normal weight and obese, further stratified by dynapenia

  1 day (one measurement )

Study Arms (4)

normal weight, not dynapenic

BMI 18.5 to 25kg/m2, waist circumference \<= 88cm, healthy women aged 60-80 years, time to complete 5 chair stands \<15 seconds

Other: observational study

normal weight, dynapenic

BMI 18.5 to 25kg/m2, waist circumference \<= 88cm,healthy women aged 60-80 years, time to complete 5 chair stands \>15 seconds

Other: observational study

obese, not dynapenic

BMI 30 to 40kg/m2, waist circumference \> 88cm, healthy women aged 60-80 years, time to complete 5 chair stands \<15 seconds

Other: observational study

obese, dynapenic

BMI 30 to 40kg/m2, waist circumference \> 88cm, women aged 60-80 years, time to complete 5 chair stands \>15 seconds

Other: observational study

Interventions

observational study OTHER

observational study

normal weight, dynapenic; normal weight, not dynapenic; obese, dynapenic; obese, not dynapenic

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy Caucasian Women Recruited from around South Yorkshire and Merseyside, UK

You may qualify if:

• Caucasian
• Female
• BMI 18.5-25 or 30-40kg/m2
• Ages 60-80 years
• Sufficiently mobile to undergo scanning and biomechanical testing
• Able to remain motionless during scans
• Able and willing to participate in the study and provide written informed consent

You may not qualify if:

• BMI 18.5-25kg/m2 AND waist circumference \>88cm i.e. normal weight AND abdominally obese
• BMI 30-40kg/m2 AND waist circumference \<88cm i.e. obese AND not abdominally obese
• History of any long-term immobilisation (duration greater than 2 weeks in the past 12 months)
• History of hospital admission in the past 3 months
• History of recent significant weight loss (5% in 3 months or 10% in 6 months)
• Diabetes mellitus
• History of current conditions which may affect muscle metabolism
• Malabsorption syndromes e.g. inflammatory bowel disease, pancreatic insufficiency etc.
• Chronic renal disease
• Diagnosed eating disorder
• Conditions which prevent the undertaking or analysis of the MRI and DXA scans or the interpretation of their results e.g. hip prosthesis, metal implants etc.
• Conditions which prevent the undertaking of the fatigue protocols e.g. hypertension etc.
• Use of medications or treatment known to affect muscle metabolism
• o Anabolic steroids, glucocorticoids, antiretrovirals etc.
• Excessive alcohol intake defined as greater than 21 units per week

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator
• University of Liverpool: collaborator

Study Sites (1)

University of Sheffield/Sheffield Teaching Hospitals

Sheffield, South Yorkshire, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Obesity; Sarcopenia

Interventions

Observation

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Jennifer Walsh

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: March 9, 2020
• Study Start: September 1, 2021
• Primary Completion: March 17, 2023
• Study Completion: March 17, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

GB (1)