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

NCT07421024 | Not Yet Recruiting Phase 2

• 2 other identifiers: ATRH-25045258
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Overweight and Obesity

Keywords

beta2; muscle; atr-258; adrenergic; biased signaling

Outcome Measures

Primary Outcomes (1)

• Intensity of β2-AR downstream signaling pathways (GRK, cAMP/PKA, and β-arrestin) in type I and type II muscle fibers

  Assessed in vastus lateralis biopsies at rest

  Before and 4 hours after ATR-258 ingestion on day 1, 29, and 56.

Secondary Outcomes (10)

• Peripheral glucose clearance including OGTT-derived outcomes

  Pre and post 12 weeks of daily ATR-258 ingestion. Post visit conducted 3-5 days after last day of ATR-258 ingestion.

• Lean mass

  Day 1, 29, and 56

• Continous ECG and heart rate

  A 5-day baseline period, and day 1-5, day 15-20, and day 29-34 of ATR-258 administration.

• Phosphorylation of rpS6, mTOR, and Akt in type I and type II muscle fibers

  Day 1, 29 and, 56.

• Muscle fiber cross-sectional area (type I and type II)

  Day 1, 29, and 56

Study Arms (1)

ATR-258

EXPERIMENTAL

Daily oral ATR-258

Drug: ATR-258

Interventions

ATR-258 DRUG

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

ATR-258

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men
• Age 21-45 years
• BMI 25-35 kg/m\^2
• Body fat percentage 25-40%
• Lean Mass Index 14-22

You may not qualify if:

• Regular use of or allergy to β2-agonists
• Serious adverse reactions to β2-agonists
• Current smoker
• Regular use of medication (except OTC allergy or analgesics)
• Abnormal ECG before or after β2-AR stimulation
• Hypertension
• Reduced kidney function (eGFR \< 90 ml/min/1.73m\^2)
• Cardiovascular, metabolic, gastrointestinal, renal, or pulmonary disease
• Psychiatric or neurological disorders affecting compliance/safety reporting
• Cancer history within the last 5 years
• Substance abuse or alcohol intake \>14 units/week

Sponsors & Collaborators

• Morten Hostrup, PhD: lead
• Atrogi AB: collaborator
• University of Copenhagen: collaborator
• Stockholm University: collaborator

Study Sites (1)

University of Copenhagen, August Krogh Section for Human & Molecular Physiology

Copenhagen, 2100, Denmark

Location

MeSH Terms

Conditions

Overweight; Obesity; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Morten Hostrup, PhD, MD

CONTACT

+45 24474785; mhostrup@nexs.ku.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, MD

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 19, 2026
• Study Start: February 20, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)