The effect of a beta-3 adrenergic receptor agonist on metabolic disease in humans.

Status

Not yet recruiting

Phases

Unknown

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12618001449224

Acronym

N/A

Enrollment

Registered

2018-08-28

Start date

2018-08-31

Completion date

2020-10-01

Last updated

2019-08-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

This proposal will determine whether a beta-adrenoceptor agonist can reduce hepatic fat content and improve metabolic control in obese humans. Accumulation of hepatic fat is an early onset and causative factor in liver and obesity-related metabolic diseases and reversal can delay or prevent sequelae. However there are currently no drugs available on-label to treat fatty liver. Increasing daily energy expenditure decreases liver fat independent of weight loss in rodents. Beta-adrenoceptor activation increases energy expenditure in rodents and humans. This proposal will therefore employ a randomised, placebo-controlled, parallel study design in combination with clinically relevant metabolic endpoints to test whether chronic treatment with a beta-adrenoceptor agonist can decrease liver fat in humans.

Interventions

Participants will receive a single daily oral dose of mirabegron or matched placebo (cellulose) for three months. Adherence to the protocol will be monitored by quantifying tablets returned.

Study design

Allocation

Randomised controlled trial

Intervention model

Parallel

Primary purpose

Treatment

Masking

Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

All

Age

20 Years to 50 Years

Healthy volunteers

Inclusion criteria

Age 20-50 years BMI: 30-40 kg/m2 HOMA-IR: greater than or equal to 2.0

Exclusion criteria

Alcohol consumption >3 (male) or >2 (female) standard drinks per day Blood ALT concentration >3 times upper limit of normal (ULN) (ULN: female <20 IU/l, male <30 IU/l) Hepatitis or autoimmune liver disease History of type 1 or 2 diabetes History of obstructive urinary symptoms History of established cardiovascular disease (prior hospitalisation or medication for any cardiovascular disease or risk factor) Currently taking any prescription medications that alter cardiometabolic parameters, prior use of anti-hypertensive medications and medications primarily acting via ß-ARs. Oral contraceptives are acceptable if treatment has been established for greater than 6 months. Smoking Established renal disease or eGFR <60 ml/min/1.73m2 Pregnant or breastfeeding women History of cancer other than non-melanoma skin cancer History of major psychiatric illness, psychosis or major depressive disorder

Outcome results