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Trial registered on ANZCTR


Registration number
ACTRN12614000689673
Ethics application status
Approved
Date submitted
12/06/2014
Date registered
30/06/2014
Date last updated
16/06/2021
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
16/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Biological actions of estradiol in men trial
Scientific title
The effects of estradiol on bone architecture and fat mass in men with prostate cancer
Secondary ID [1] 284785 0
Nil
Universal Trial Number (UTN)
Trial acronym
BAEMT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone loss
 292161 0
Prostate Cancer 292245 0
Hypogonadism 304421 0
Condition category
Condition code
Musculoskeletal 292498 292498 0 0
Osteoporosis
Cancer 292542 292542 0 0
Prostate
Metabolic and Endocrine 303752 303752 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Estradiol transdermal gel 0.9 mg/d (1mL daily) for 6 months
Intervention code [1] 289576 0
Treatment: Drugs
Comparator / control treatment
Matching placebo transdermal gel 1mL daily for 6 months
Control group
Placebo

Outcomes
Primary outcome [1] 292358 0
Total volumetric bone mineral density at tibia measured by high resolution peripheral quantitative computed tomography (HR-pQCT).
Timepoint [1] 292358 0
6 months
Primary outcome [2] 303622 0
Total fat mass by DEXA scan
Timepoint [2] 303622 0
6 months
Secondary outcome [1] 337926 0
Bone remodeling markers (P1NP, CTX) assessed by serum assay.
Timepoint [1] 337926 0
6 months
Secondary outcome [2] 337927 0
Cortical porosity as measured by HR-pQCT
Timepoint [2] 337927 0
6 months
Secondary outcome [3] 337928 0
Visceral and subcutaneous abdominal fat by DEXA scan
Timepoint [3] 337928 0
6 months
Secondary outcome [4] 337929 0
Lean body mass by DEXA scan
Timepoint [4] 337929 0
6 months
Secondary outcome [5] 337930 0
Insulin resistance as estimated by HOMA-IR
Timepoint [5] 337930 0
6 months
Secondary outcome [6] 337931 0
Cognitive scores in 6 domains measured by a short cognitive battery
- Processing speed (Detection Test)
- Attention (Identification Test)
- Visual memory (One Card Learning Test)
- Working memory (One Back Test)
- Executive function (Groton Maze Learning Test)
- Verbal learning (International Shopping List Test)
Timepoint [6] 337931 0
6 months
Secondary outcome [7] 337932 0
Anatomical differences on brain MRI scanning (MPRAGE T1 anatomical images)
Timepoint [7] 337932 0
6 months
Secondary outcome [8] 337933 0
Trabecular number, thickness, separation and trabecular bone volume/tissue volume as measured by HR-pQCT
Timepoint [8] 337933 0
6 months
Secondary outcome [9] 337934 0
Functional MRI tasks
- Emotion Recognition
- Verbal Memory
- Mental Rotation
Timepoint [9] 337934 0
6 months
Secondary outcome [10] 337935 0
Areal bone mineral density as measured by DEXA scanning
Timepoint [10] 337935 0
6 months
Secondary outcome [11] 337993 0
Total volumetric bone mineral density at radius as measured by HR-pQCT.
Timepoint [11] 337993 0
6 months
Secondary outcome [12] 337994 0
Matrix mineral density as measured by HR-pQCT
Timepoint [12] 337994 0
6 months
Secondary outcome [13] 339661 0
Hot Flushes as measured by the Mayo Clinic Hot Flash Diary
Timepoint [13] 339661 0
6 months
Secondary outcome [14] 339662 0
Prostate cancer specific quality of life as measured by the FACT-P questionnaire.
Timepoint [14] 339662 0
6 months
Secondary outcome [15] 339663 0
Sexual function as measured by the IIEF-5 questionnaire
Timepoint [15] 339663 0
6 months
Secondary outcome [16] 339664 0
Hypogonadal symptoms as measured by the Aging Male Symptoms Score
Timepoint [16] 339664 0
6 months
Secondary outcome [17] 339665 0
Depression using the Hospital and Anxiety Depression Score
Timepoint [17] 339665 0
6 months
Secondary outcome [18] 372435 0
Cortical volumetric bone mineral density at tibia measured by HR-pQCT.
Timepoint [18] 372435 0
6 months
Secondary outcome [19] 372436 0
Cortical volumetric bone mineral density at radius measured by HR-pQCT.
Timepoint [19] 372436 0
6 months
Secondary outcome [20] 372437 0
Cortical area at distal tibia as measured by HR-pQCT.
Timepoint [20] 372437 0
6 months
Secondary outcome [21] 372438 0
Cortical area at distal radius as measured by HR-pQCT.
Timepoint [21] 372438 0
6 months
Secondary outcome [22] 372439 0
Structural fragility score derived from HR-pQCT parameters.
Timepoint [22] 372439 0
6 months

Eligibility
Key inclusion criteria
1. Men with prostate cancer receiving gonadotropin-releasing hormone agonists or antagonists to suppress androgen production
2. Androgen Deprivation Therapy intended to continue for at least 6 months
3. Able and willing to comply with the study protocol requirements
Minimum age
No limit
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Bone metastases within imaging fields detectable by conventional imaging (e.g. CT scanning, bone scanning)
2. Significantly impaired performance status (ECOG > 2)
3. Previous history of deep vein thrombosis or pulmonary embolism
4. Stroke, transient ischaemic attack, myocardial infarction, or angina within the previous 12 months
5. New York Heart Association class 3-4 heart failure
6. Systolic blood pressure of 160 mmHg or higher or diastolic blood pressure of 100 mmHg or higher, or both.
7. Previous history of breast cancer
8. Current oral glucocorticoid therapy
9. Any current or previous antiresorptive therapy
10. Recreational drug use, alcohol dependence, known HIV/AIDS or any disease which is likely to lead to serious illness or death within the study period
11. Inability to understand sufficient English to give informed consent.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
COVID-19 pandemic resulted in a human research ethics committee mandated shut down in recruitment. Further recruitment may have been possible in future from an ethics stand point but funding, staff, facilities were not able to be guaranteed for a future commencement of recruitment.
Date of first participant enrolment
Anticipated
1/11/2017
Actual
8/11/2017
Date of last participant enrolment
Anticipated
30/06/2020
Actual
27/02/2020
Date of last data collection
Anticipated
Actual
24/08/2020
Sample size
Target
130
Accrual to date
Final
78
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8815 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 16939 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 289401 0
Self funded/Unfunded
Name [1] 289401 0
Address [1] 289401 0
Country [1] 289401 0
Primary sponsor type
University
Name
University of Melbourne
Address
Dept. of Medicine
146 Studley Road
Heidelberg 3082
Victoria
Country
Australia
Secondary sponsor category [1] 288083 0
Hospital
Name [1] 288083 0
Austin Health
Address [1] 288083 0
146 Studley Road
Heidelberg 3082
Victoria
Country [1] 288083 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291161 0
Austin Health
Ethics committee address [1] 291161 0
146 Studley Road
Heidelberg 3082
Victoria
Ethics committee country [1] 291161 0
Australia
Date submitted for ethics approval [1] 291161 0
01/08/2014
Approval date [1] 291161 0
08/08/2017
Ethics approval number [1] 291161 0
HREC/16/Austin/98

Summary
Brief summary
This study will evaluate the effect of estradiol on bone architecture and fat mass in men with prostate cancer.

Who is it for?
You may be eligible to join this study if you are male, and have been diagnosed with prostate cancer for which you are about to commence treatment with GnRH agonists or antagonists to suppress androgen production (Androgen Deprivation Therapy; ADT)

Study details
Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will apply estradiol gel to the skin once daily for six months. Participants in the other group will apply a placebo gel (contains no active ingredients) to the skin once daily for six months.

Recent evidence suggests that in men, some important biological actions attributed to testosterone are mediated via its metabolite, estradiol, rather than directly via the androgen receptor. We propose to use ADT given to men with prostate cancer as a unique model of severe long-term untreated hypogonadism to investigate biological actions of estradiol when testosterone is reduced to castrate levels.

On completion of treatment at six months, participants will undergo a high resolution peripheral quantitative computed tomography (HR-pCT) scan to assess bone architecture and a dual-energy X-ray absorptiometry (DEXA) scan to assess fat mass.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49154 0
A/Prof Mathis Grossmann
Address 49154 0
Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia
Country 49154 0
Australia
Phone 49154 0
+61394965000
Fax 49154 0
Email 49154 0
mathisg@unimelb.edu.au
Contact person for public queries
Name 49155 0
Dr Nicholas Russell
Address 49155 0
Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia
Country 49155 0
Australia
Phone 49155 0
+61394965000
Fax 49155 0
Email 49155 0
nicholas.russell@austin.org.au
Contact person for scientific queries
Name 49156 0
Dr Nicholas Russell
Address 49156 0
Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia
Country 49156 0
Australia
Phone 49156 0
+61394965000
Fax 49156 0
Email 49156 0
nicholas.russell@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results.
When will data be available (start and end dates)?
From publication of results for a period of 5 years
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Access subject to approvals by Principal Investigator (nicholas.russell@austin.org.au)
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary