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Trial registered on ANZCTR


Registration number
ACTRN12618001449224
Ethics application status
Approved
Date submitted
7/06/2018
Date registered
28/08/2018
Date last updated
28/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of a beta-3 adrenergic receptor agonist on metabolic disease in humans.
Scientific title
The effect of a beta-3 adrenergic receptor agonist on metabolic disease in humans.
Secondary ID [1] 295122 0
None
Universal Trial Number (UTN)
U1111-1215-3744
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Hepatic steatosis 308214 0
Condition category
Condition code
Metabolic and Endocrine 307243 307243 0 0
Diabetes
Metabolic and Endocrine 307244 307244 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 301456 0
Treatment: Drugs
Comparator / control treatment
both treatments will be encapsulated into a single pill. The control treatment will involve packing cellulose powder (a safe and metabolically inert component of food) into the capsules
Control group
Placebo

Outcomes
Primary outcome [1] 306199 0
liver fat content via 1H-magnetic resonance spectroscopy
Timepoint [1] 306199 0
within 72 hours prior to initiation and 48 hours after completion of the three month intervention
Secondary outcome [1] 347819 0
Homeostatic model assessment of insulin resistance (HOMA-IR; calculated from fasting glucose and fasting insulin concentrations).

Fasting glucose and insulin concentrations will be measured from whole blood according to clinical diagnostic standard at a NATA/RCPA accredited pathology laboratory.
Timepoint [1] 347819 0
within 48 hours prior to initiation and 48 hours after completion of the three month intervention

Eligibility
Key inclusion criteria
Age 20-50 years
BMI: 30-40 kg/m2
HOMA-IR: greater than or equal to 2.0
Minimum age
20 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An independent agent (Alfred Hospital Clinical Trials Pharmacy (CTP) staff member) will be responsible for allocation of treatment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Alfred CTP staff will use software (eg MS Excel) to generate a random order sequence for allocation of treatment
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Treatment effects will be assessed as the percentage change in variables from pre- to post-intervention between groups via ANCOVA with age, gender and indices of body size (BMI, body fat content and/or body mass) included as covariates. Statistical significance will be accepted at p<0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/08/2018
Actual
Date of last participant enrolment
Anticipated
1/10/2020
Actual
Date of last data collection
Anticipated
31/12/2020
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 22915 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 299715 0
Other
Name [1] 299715 0
Baker Heart and Diabetes Institute
Country [1] 299715 0
Australia
Primary sponsor type
Other
Name
Baker Heart and Diabetes Institute
Address
75 Commercial Rd
Melbourne, Vic,
3004
Country
Australia
Secondary sponsor category [1] 299047 0
None
Name [1] 299047 0
NA
Address [1] 299047 0
N/A
Country [1] 299047 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300603 0
Alfred Hospital Ethics Committee [EC00315]
Ethics committee address [1] 300603 0
The Alfred, Office of Ethics & Research Governance
PO Box 315
Prahran VIC 3181
Ethics committee country [1] 300603 0
Australia
Date submitted for ethics approval [1] 300603 0
01/07/2018
Approval date [1] 300603 0
16/08/2018
Ethics approval number [1] 300603 0

Summary
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.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 84186 0
Dr Andrew Carey
Address 84186 0
Baker Heart and Diabetes Institute
PO Box 6492
Melbourne, Vic
3004
Country 84186 0
Australia
Phone 84186 0
+61385321251
Fax 84186 0
Email 84186 0
andrew.carey@baker.edu.au
Contact person for public queries
Name 84187 0
Dr Andrew Carey
Address 84187 0
Baker Heart and Diabetes Institute
PO Box 6492
Melbourne, Vic
3004
Country 84187 0
Australia
Phone 84187 0
+61385321251
Fax 84187 0
Email 84187 0
andrew.carey@baker.edu.au
Contact person for scientific queries
Name 84188 0
Dr Andrew Carey
Address 84188 0
Baker Heart and Diabetes Institute
PO Box 6492
Melbourne, Vic
3004
Country 84188 0
Australia
Phone 84188 0
+61385321251
Fax 84188 0
Email 84188 0
andrew.carey@baker.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.