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Overweight and ObesityPhase 2GAINNCT07421024

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

A Phase 2 study testing ATR-258 in people with Overweight and Obesity, run by Morten Hostrup, PhD at 1 site in Denmark.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for
Overweight and Obesity
What is being tested?
ATR-258
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteDenmark
Study dates
19 Feb 2026to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

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

    Copenhagen, 2100

Other trials in Denmark

About this study

Official title: G Protein-Coupled Receptor Kinase (GRK)-Biased Signaling Via β2-Adrenergic Receptors and Downstream Activation and Its Role for Protein Synthesis-Regulating Kinases, Function and Receptor Desensitization in Human Skeletal Muscle

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 up- and downstream signaling, fiber-type specificity, and potential receptor desensitization with repeated stimulation along with functional read-outs, tissue distribution, cardiovascular response and tolerability.

Read the 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 lower extremity muscle function/power 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.

Being tested
ATR-258
Keywords
beta2, muscle, atr-258, adrenergic, biased signaling
Medical subject headings
Overweight, Obesity, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATR-258Drug

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

Study groups in NCT07421024
Study groupRoleWhat they receive
ATR-258ExperimentalDaily oral ATR-258
Receives: Drug: ATR-258

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intensity of β2-AR downstream signaling pathways (e.g. GRK, cAMP/PKA, β-arrestin, rpS6) in type I and type II muscle fibers

    Assessed in vastus lateralis biopsies at rest

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

Secondary outcomes (10)

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

    In response to ATR-258 ingestion

    Measured: Day 1, 29 and, 56.

  2. Lean/fat mass

    Measured by DXA scan

    Measured: Day 1, 15, 29, and 56

  3. Muscle function

    Participants will perform lower extremity peak exercise and a one-legged knee-extensor exercise protocol to exhaustion before and after the full intervention to assess muscle power and endurance

    Measured: Pre and post 8 weeks of daily ATR-258 ingestion. Post visit conducted 2-5 days after last day of ATR-258 ingestion.

  4. Peripheral glucose clearance including OGTT-derived outcomes

    Measured: Pre and post 8 weeks of daily ATR-258 ingestion. Post visit conducted 2-5 days after last day of ATR-258 ingestion.

  5. β2-adrenergic receptor content in type I and type II muscle fibers

    Measured by western blotting

    Measured: On day 1, 29 and 56

  6. Resting metabolic rate (incl. carbohydrate and fat oxidation)

    Measured by indirect calorimetry

    Measured: Before and 1, 2, 4 and 8 hours after ATR-258 ingestion on day 1, 15, 29, and 56.

  7. Femoral arterial blood flow

    Measured by Doppler.

    Measured: Before and 1, 2, 4 and 8 hours after ATR-258 ingestion on day 1, 15, 29, and 56.

  8. 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.

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

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

    Measured by histochemical analysis

    Measured: Day 1, 29, and 56

  10. Maximal electrically-stimulated muscle force development and relaxation

    Isometric quadriceps. Measured seated with leg in 90 degree angle and attached to strain gauge.

    Measured: Pre and post 8 weeks of daily ATR-258 ingestion. Post visit conducted 2-5 days after last day of ATR-258 ingestion.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2026
  2. Study start19 Feb 2026
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07421024
Sponsor's protocol ID
ATR
Other IDs
H-25045258
Acronym
GAIN
Status last verified
Oct 2026
First submitted
30 Jan 2026
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ATR-258 in people with Overweight and Obesity, run by Morten Hostrup, PhD at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intensity of β2-AR downstream signaling pathways (e.g. GRK, cAMP/PKA, β-arrestin, rpS6) in type I and type II muscle fibers (time frame: Before and 4 hours after ATR-258 ingestion on day 1, 29, and 56.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07421024.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.

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