NCT07421024

Biased GRK Signaling Via β2-Adrenergic Receptors in Human Skeletal Muscle

Biased G Protein-Coupled Receptor Kinase Signaling Via β2-Adrenergic Receptors and Downstream Activation of Protein Synthesis-Regulating Kinases and Receptor Desensitization in Human Skeletal Muscle

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Morten Hostrup, PhD · Academic / Other
• Sex: Male
• Age: 21 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This longitudinal mechanistic physiological study examines biased β2-adrenergic receptor (β2-AR) signaling in human skeletal muscle, with emphasis on G protein-coupled receptor kinase (GRK)-mediated pathways. Participants will receive daily oral dosing of the GRK-selective long-acting β2-agonist ATR-258 for 8 weeks. Muscle biopsies and physiological measurements will quantify GRK-, cAMP/PKA-, and β-arrestin-related signaling, fiber-type specificity, and potential receptor desensitization with repeated stimulation.

Detailed description

Healthy men with overweight/obesity will complete an 8-week intervention with daily oral ATR-258 (0.5-2.5 mg/day). On experimental days (Days 1, 15, 29, and 56), β2-AR signaling sensitivity will be assessed before and after stimulation (1-2, 4, and 8 hours) using blood biomarkers, hemodynamics, indirect calorimetry, and muscle function testing. Muscle biopsies (vastus lateralis) will be obtained at rest and 4 hours after stimulation on Days 1, 29, and 56 to quantify downstream signaling (GRK, cAMP/PKA, β-arrestin), phosphorylation of rpS6/mTOR/Akt, β2-AR content, and muscle fiber morphology.

Conditions

• Overweight and Obesity

Interventions

Type	Name	Description
DRUG	ATR-258	Daily oral ATR-258 for 8 weeks with repeated experimental assessment days (Days 1, 15, 29, 56).

Timeline

• Start date: 2026-02-20
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2026-02-19
• Last updated: 2026-02-19

Locations

1 site across 1 country: Denmark