ANZCTR - Registration

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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

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]

Nil

Universal Trial Number (UTN)

Trial acronym

BAEMT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Bone loss

Prostate Cancer

Hypogonadism

Condition category

Condition code

Musculoskeletal

Osteoporosis

Cancer

Prostate

Metabolic and Endocrine

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]

Treatment: Drugs

Comparator / control treatment

Matching placebo transdermal gel 1mL daily for 6 months

Control group

Placebo

Outcomes

Primary outcome [1]

Total volumetric bone mineral density at tibia measured by high resolution peripheral quantitative computed tomography (HR-pQCT).

Timepoint [1]

6 months

Primary outcome [2]

Total fat mass by DEXA scan

Timepoint [2]

6 months

Secondary outcome [1]

Bone remodeling markers (P1NP, CTX) assessed by serum assay.

Timepoint [1]

6 months

Secondary outcome [2]

Cortical porosity as measured by HR-pQCT

Timepoint [2]

6 months

Secondary outcome [3]

Visceral and subcutaneous abdominal fat by DEXA scan

Timepoint [3]

6 months

Secondary outcome [4]

Lean body mass by DEXA scan

Timepoint [4]

6 months

Secondary outcome [5]

Insulin resistance as estimated by HOMA-IR

Timepoint [5]

6 months

Secondary outcome [6]

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]

6 months

Secondary outcome [7]

Anatomical differences on brain MRI scanning (MPRAGE T1 anatomical images)

Timepoint [7]

6 months

Secondary outcome [8]

Trabecular number, thickness, separation and trabecular bone volume/tissue volume as measured by HR-pQCT

Timepoint [8]

6 months

Secondary outcome [9]

Functional MRI tasks
- Emotion Recognition
- Verbal Memory
- Mental Rotation

Timepoint [9]

6 months

Secondary outcome [10]

Areal bone mineral density as measured by DEXA scanning

Timepoint [10]

6 months

Secondary outcome [11]

Total volumetric bone mineral density at radius as measured by HR-pQCT.

Timepoint [11]

6 months

Secondary outcome [12]

Matrix mineral density as measured by HR-pQCT

Timepoint [12]

6 months

Secondary outcome [13]

Hot Flushes as measured by the Mayo Clinic Hot Flash Diary

Timepoint [13]

6 months

Secondary outcome [14]

Prostate cancer specific quality of life as measured by the FACT-P questionnaire.

Timepoint [14]

6 months

Secondary outcome [15]

Sexual function as measured by the IIEF-5 questionnaire

Timepoint [15]

6 months

Secondary outcome [16]

Hypogonadal symptoms as measured by the Aging Male Symptoms Score

Timepoint [16]

6 months

Secondary outcome [17]

Depression using the Hospital and Anxiety Depression Score

Timepoint [17]

6 months

Secondary outcome [18]

Cortical volumetric bone mineral density at tibia measured by HR-pQCT.

Timepoint [18]

6 months

Secondary outcome [19]

Cortical volumetric bone mineral density at radius measured by HR-pQCT.

Timepoint [19]

6 months

Secondary outcome [20]

Cortical area at distal tibia as measured by HR-pQCT.

Timepoint [20]

6 months

Secondary outcome [21]

Cortical area at distal radius as measured by HR-pQCT.

Timepoint [21]

6 months

Secondary outcome [22]

Structural fragility score derived from HR-pQCT parameters.

Timepoint [22]

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

Sex

Males

Can healthy volunteers participate?

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

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Heidelberg Repatriation Hospital - Heidelberg West

Recruitment postcode(s) [1]

3081 - Heidelberg West

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

University

Name

University of Melbourne

Address

Dept. of Medicine
146 Studley Road
Heidelberg 3082
Victoria

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Austin Health

Address [1]

146 Studley Road
Heidelberg 3082
Victoria

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health

Ethics committee address [1]

146 Studley Road
Heidelberg 3082
Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/08/2014

Approval date [1]

08/08/2017

Ethics approval number [1]

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

A/Prof Mathis Grossmann

Address

Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia

Country

Australia

Phone

+61394965000

Fax

[email protected]

Contact person for public queries

Name

Nicholas Russell

Address

Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia

Country

Australia

Phone

+61394965000

Fax

[email protected]

Contact person for scientific queries

Name

Nicholas Russell

Address

Department of Medicine Austin Health
The University of Melbourne
145 Studley Road, Heidelberg, VIC 3084, Australia

Country

Australia

Phone

+61394965000

Fax

[email protected]

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 ([email protected])

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

Source	Title	Year of Publication	DOI
Embase	Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial.	2022	https://dx.doi.org/10.1111/cen.14689
Embase	Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.	2022	https://dx.doi.org/10.1530/EJE-22-0227
Embase	Effects of oestradiol treatment on hot flushes in men undergoing androgen deprivation therapy for prostate cancer: a randomised placebo-controlled trial.	2022	https://dx.doi.org/10.1530/EJE-22-0318

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically