IMAT Quality in Aging
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Calf muscle strengthening.
- Who it may be relevant to
- Registry conditions: Aging. Basic parameters: 65 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Targeting Intramuscular Adipose Quality in Aging
Overview
This study will test the central hypothesis that fat within the muscle, or intramuscular adipose tissue (IMAT), exhibits elevated damage and pro-inflammatory signaling with aging, both of which are reduced by progressive resistance exercise (PRE). Sixteen older adults 65-80 years old will be recruited and complete a 12 week calf PRE intervention. Calf muscle strength, composition (measured by computed tomography) and muscle biopsies will be collected before and after the intervention. Histology, transcriptomic and secretomic tests will be completed to assess signs of damage and inflammation.
Detailed description
Sixteen older adult (65-80 years) will be recruited from existing databases and screened for potential participation by phone. The Rapid Assessment of Physical Activity (RAPA) will be completed, to include those who are underactive (scores 3-5). Individuals who meet the inclusion criteria will attend an in-person screening where their calf muscle strength, physical performance and safety for muscle biopsy (via complete blood count with differential and prothrombin time/international normalized raio on blood draw) will be assessed. Individuals deemed safe to participate and who give informed consent will attend a second visit which will include a computed tomography (CT) scan of the lower leg and ultrasound-guided gastrocnemius muscle+IMAT biopsy. One week later, participants will begin the ankle plantarflexor-targeted progressive resistance exercise (PRE) program which will be delivered in a group Zoom format with a trained therapist 3 times per week for 12 weeks. One week following completion of the PRE program, participants will return for follow-up strength measures, CT, and biopsy. This will complete their participation. In the lab, biopsies will be subdivided for bulk ribonucleic acid sequencing (RNAseq), explant culture and histology. Bulk RNAseq will be used to identify age- and exercise-responsive genes that encode secreted proteins. These putative secreted signals will be validated by protein quantification in explant culture. The cellular origin of validated signals will then be mapped by RNA in situ hybridization (RNAscope) on the portion of the biopsy allocated to histology. Sections will also used to identify senescent cells, inflammatory macrophages and beige adipocytes.
Interventions
- Other Calf muscle strengthening
The calf intervention will be delivered 3x/wk for 12 weeks over zoom, in small groups. There are 3 exercises 1) standing heel rise, 2) seated heel rise, and 3) long sitting ankle plantarflexion. The exercises will be overloaded using a weighted vest, body weight, and/or theraband. Exercises will be progressed as strength improves.
Primary outcome measures
- Biopsy: Senescent cell density [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
Secondary outcome measures (12)
- Total plantarflexor muscle volume (CT) (Cm^3) [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Plantarflexor Compartment Intramuscular Fat Volume (cm^3) [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Plantarflexor peak torque (Newton-meters) [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Stair Climb Power (W) [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Walking Speed (meters/second) [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Physical Performance Test Total Score [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: Adipocyte size [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: Macrophage density [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: Beige adipocyte density [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: Differentially expressed genes and pathways [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: cytokine secretion [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
- Biopsy: Spatially resolved gene expression [Time frame: Baseline and post-intervention (approximately 14 weeks after baseline)]
Eligibility criteria
Inclusion criteria
- Rapid Assessment of Physical Activity scores between 3 and 5
- Able to don and doff the weighted vest
- Access to a smart phone and ability to navigate the phone to enter and manage a zoom intervention
- Commitment and availability to attend a virtual 40-minute intervention 3x per week for 12 weeks
Exclusion criteria
- Contraindications to radiation exposure (e.g. Women who are pregnant, previous high radiation exposure)
- Bleeding disorders
- Lower extremity trauma/surgery/injury or neuropathy that would impact muscle structure and function or ability to complete exercise intervention
- Diabetes mellitus, cardiovascular disease, peripheral vascular disease, cancer, stage 4 hypertension, anemia, connective tissue disorder
- Neurological disorder (e.g. stroke, Parkinson's disease, multiple sclerosis, spinal cord injury)
- Medications: insulin, glucagon-like peptide-1 (GLP1) agonists, sex hormone replacement therapy, chronic NSAIDs, anticoagulation therapy, cholesterol lowering medications such as statins
- Unable to safely perform the progressive resistance exercise (e.g. Vestibular or balance issues that make performing the intervention unsafe, severe osteoporosis or general fragility that limits weighted vest tolerance)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Washington University — St Louis
Identifiers
NCT: NCT07506681 · 202512046 · 1R21AG091159-01A1