Effects of Glucocortioids in Human Skeletal Muscle, Adipose Tissue and Skin

Glucocorticoids Toxicity Clinical Trial

— FUSION  

Official title:

Effects of Glucocortioids in Human Skeletal Muscle, Adipose Tissue and Skin

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06145126
• Other study ID #: FUSION
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 2023
• Est. completion date: July 2025

Study information

• Verified date: October 2023
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BACKGROUND: A notorious and dreaded adverse effect of glucocorticoids (GC) is redistribution of muscle and fat mass towards muscle wasting and visceral obesity. Fibroadipogenic progenitors (FAPs) are hypothesized to mediate this process.

AIM: Utilizing human data, the investigators study the effects of GC exposure on skeletal muscle structure and function, adipose tissue and skin in healthy older subjects.

METHODS: FAPs will be analyzed in biopsies from skeletal muscles, adipose tissue and skin and further characterized using scRNA-sequencing and Fluorescence-Activated Cell Sorting. Body composition including muscle mass (DXA scan), muscle strength, spontaneous physical activity and glucose homeostasis are recorded.

PERSPECTIVES: The investigators combine translational research with multidisciplinary and international collaboration to elucidate the pathophysiology of GC excess, which is of significant clinical interest since 3% of the Danish population receive GC treatment.

Description:

Design: randomized, double blind, placebo-controlled trial. The aim is to study the effect of short-term GC exposure on skeletal muscle, skin , adipose tissue in 12 healthy adults above the age of 50 years. This age group is close to that of patients receiving short-term, high dose anti-inflammatory prednisolone treatment and thus provides a bridge between a clinically observered problem. The participants will be randomized to receive either prednisolone (37,5mg/d) or placebo treatment for five consecutive days. In addition to muscle, skin, and adipose tissue biopsies and body composition measurement (DXA), each participant will undergo the following measurements before and after the intervention: spontaneous physical activity (actigraphy), ambulatory 24-hour blood pressure, continuous glucose monitoring (CGM), pulse wave velocity (PWV), and muscle strength. Each participant is studied before and after the 5-day treatment period.

Outcomes:

• FAPs expression in skeletal muscle and adipose tissue:

• Fluorescence Activated Cell Sorting (FACS) mediated quantification, isolation and transcriptomic profiling at population and single-cell level of FAPs, and immunological cells

• Time-to-first division of isolation FAPs

• In vitro fibro- and adipogenic differentiation of FAPs

• Single cell transcriptome analysis (scRNA-seq) to profile cell types in a hypothesis-generating perspective.

• Functional outcomes: Muscle mass and strength (DXA scan and isometric quadriceps strength) and spontaneous physical activity (actigraphy)

• Metabolic outcomes: circadian blood glucose and blood pressure, and basal insulin sensitivity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: July 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Written and oral consent prior to study beginning

• Age of or above 50 years

• Healthy (uncomplicated hypertension and hypercholesteroleamia is accepted)

• BMI of or below 35

Exclusion Criteria:

• Consumption of glucocorticoid pharmaceuticals (inhalation steroids, intra-articular or intra-muscular injections, steroid creme group IV-V used in the genital area). Allowed pharmaceuticals: ocular drops, nasal sprays/drops, steroid creme group I-III, steroid creme group IV-V used in non-genital areas

• Alcohol consumption of more than 21 units per week

• Consumption of strong CYP3A4 inhibitors/inducers

• Serious comorbidity (heart, liver, or kidney failure, as well as cooncurrent cancer/chemotherapy treatment)

• High daily activity level (more than 30min per day or more than 2 organized workouts per week)

Related Conditions & MeSH terms

• Glucocorticoids Toxicity
• Iatrogenic Effect

Intervention

Other:
• Prednisolone
Predisolone is used as a tool to elicit a physiological response (toolbox trial) and not as a pharmaceutical agent/treatment.
• Placebo
Placebo to predinisolon

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FAPs expression in skeletal muscle, adipose tissue, and skin	Single cell transcriptome analysis (scRNA-seq) to profile cell types in a hypothesis-generating perspective.	2 Years
Secondary	Dual X-ray scan (DXA)	Bodycomposition (grams)	2 Years
Secondary	Metabolic outcomes - Circadian blood glucose	Blood monitoring using Dexcom censor (unit: mmol/L)	Years
Secondary	Dynamometer	Isometric muscle contraction (power)	2 Years
Secondary	24h blood pressure	Systolic and diastolic (mmHg)	2 Years
Secondary	Basal insulin sensitivity.	Blood samples (pmol/L)	2 Years
Secondary	Activity level	Spontanous activity level using a wrist ban monitor (ActiGraph)	2 Years