Health TrialsbyHealthPanel

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

ConditionOverweight and Obesity
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age21-45
SponsorMorten Hostrup, PhD

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Healthy men

Age 21-45 years

BMI 25-35 kg/m²

Body fat percentage 25-40%

Disqualifiers

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)

Trial design

Design model

Single group

Treatments tested in this trial

  • ATR-258

    Drug

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

Treatment groups

10 Participants
are divided into 1 treatment group
Group A: ATR-258Experimental treatment 1 intervention

Trial outcomes

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

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

Secondary outcomes

1

Peripheral glucose clearance including OGTT-derived outcomes

Time frame
Pre and post 12 weeks of daily ATR-258 ingestion. Post visit conducted 3-5 days after last day of ATR-258 ingestion.
2

Lean mass

Measured by DXA scan

Time frame
Day 1, 29, and 56
3

Continous ECG and heart rate

Participants will wear a Holter-device for 4 x 5 days to continuously measure ECG and heart rate. The periods will be after the screening (baseline period), and after trial days on Day 1, 15, and 29.

Time frame
A 5-day baseline period, and day 1-5, day 15-20, and day 29-34 of ATR-258 administration.
4

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

In response to ATR-258 ingestion

Time frame
Day 1, 29 and, 56.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Morten Hostrup, PhD

Lead sponsor

University of Copenhagen

Sponsor institution

Atrogi AB

Collaborator

University of Copenhagen

Collaborator

Stockholm University

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: