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Trial registered on ANZCTR


Registration number
ACTRN12616000373471
Ethics application status
Approved
Date submitted
16/03/2016
Date registered
23/03/2016
Date last updated
10/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Topical estradiol add-back in hypogonadal men: dose-finding study
Scientific title
Topical estradiol add-back in hypogonadal men: dose-finding study
Secondary ID [1] 288761 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 298008 0
Hypogonadism 298009 0
Condition category
Condition code
Cancer 298168 298168 0 0
Prostate
Metabolic and Endocrine 298169 298169 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Estradiol transdermal gel either 0.9mg per day or 1.8mg per day, applied from a metered dose syringe once daily anywhere on the skin of the trunk for 4 weeks. Adherence will be monitored by weighing returned syringes.
Intervention code [1] 294200 0
Treatment: Drugs
Comparator / control treatment
Identical placebo transdermal gel (ultrasound gel) also applied from an identical metered dose syringe once daily for 4 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 297679 0
Serum estradiol level
Timepoint [1] 297679 0
Weekly from baseline to end of 4 week intervention period.
Secondary outcome [1] 321804 0
Serum Luteinizing Hormone
Timepoint [1] 321804 0
Weekly from baseline to end of 4 week intervention period.
Secondary outcome [2] 321806 0
Homeostatic model assessment of insulin resistance (HOMA-IR) calculated from serum fasting glucose and serum fasting insulin levels.
Timepoint [2] 321806 0
4 weeks compared with baseline
Secondary outcome [3] 321807 0
Serum IGF-1
Timepoint [3] 321807 0
4 weeks compared with baseline
Secondary outcome [4] 321808 0
Hot Flushes (Mayo Clinic Hot Flash Diary)
Timepoint [4] 321808 0
4 weeks compared with baseline
Secondary outcome [5] 321996 0
Serum pro collagen type 1 amino-terminal propeptide (P1NP)
Timepoint [5] 321996 0
4 weeks compared with baseline
Secondary outcome [6] 321997 0
Serum beta carboxyl-terminal type 1 collagen telopeptide (CTX)
Timepoint [6] 321997 0
4 weeks compared with baseline
Secondary outcome [7] 321998 0
Serum follicle-stimulating hormone
Timepoint [7] 321998 0
Weekly from baseline to end of 4 week intervention period
Secondary outcome [8] 321999 0
Serum total testosterone
Timepoint [8] 321999 0
Weekly from baseline to end of 4 week intervention period
Secondary outcome [9] 322000 0
Serum dihydrotestosterone
Timepoint [9] 322000 0
Weekly from baseline to end of 4 week intervention period
Secondary outcome [10] 322001 0
Serum estrone
Timepoint [10] 322001 0
Weekly from baseline to end of 4 week intervention period
Secondary outcome [11] 322002 0
Serum 5-alpha-androstane-3-alpha, 17-beta-diol
Timepoint [11] 322002 0
Weekly from baseline to end of 4 week intervention period
Secondary outcome [12] 322003 0
Serum 5-alpha-androstane-3-beta, 17-beta-diol
Timepoint [12] 322003 0
Weekly from baseline to end of 4 week intervention period

Eligibility
Key inclusion criteria
1) Men with Prostate Cancer without metastases to bone or viscera detectable on staging with computed tomography or bone scanning.
2) Receiving treatment with GnRH agonists to suppress androgen production with a planned duration of further treatment of greater than 4 weeks
Minimum age
55 Years
Maximum age
85 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1) Impaired performance status (ECOG >1)
2) History of deep vein thrombosis or pulmonary embolism
3) Stroke, transient ischaemic attack, myocardial infarction, or angina within last 12 months
4) Systolic BP > 160 or DBP > 100
5) Symptomatic heart failure (NYHA class > 1)
6) History of breast cancer
7) Pre-existing osteoporosis
8) Prior treatment with glucocorticoids or bisphosphonates
9) Diabetes Mellitus
10) Alcohol dependence or recreational drug use

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)
Yes - via central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomized into 3 groups of 12, with equal probability of allocation to
each group. Randomization will be stratified by body mass index (< 29
and >29 kg/m2). The randomization will be created using a generic randomisation template from a statistic book.
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
Phase
Phase 1
Type of endpoint(s)
Bio-availability
Statistical methods / analysis
This is an initial dose-finding study. Power calculations have not been performed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5436 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 5437 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment postcode(s) [1] 12921 0
3084 - Heidelberg
Recruitment postcode(s) [2] 12922 0
3081 - Heidelberg West

Funding & Sponsors
Funding source category [1] 293143 0
Government body
Name [1] 293143 0
National Health and Medical Research Council
Address [1] 293143 0
GPO Box 1421
Canberra ACT 2601
Country [1] 293143 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Department of Medicine (Austin Health)
145 Studley Rd
Heidelberg
VIC 3084
Country
Australia
Secondary sponsor category [1] 291932 0
Hospital
Name [1] 291932 0
Austin Health
Address [1] 291932 0
145 Studley Rd
Heidelberg
VIC 3084
Country [1] 291932 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294619 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 294619 0
145 Studley Rd
Heidelberg
VIC 3084
Ethics committee country [1] 294619 0
Australia
Date submitted for ethics approval [1] 294619 0
07/03/2016
Approval date [1] 294619 0
14/06/2016
Ethics approval number [1] 294619 0

Summary
Brief summary
The primary purpose of this trial is to determine the ideal dose of estradiol to give to men receiving androgen deprivation therapy (ADT) for prostate cancer, in order to replace the normal estradiol levels that they would have if they were not taking ADT.

Who is it for?
You may be eligible to participate in this trial if you are aged 55 to 80 years of age, and have been diagnosed with non-metastatic Prostate Cancer (T1-3NxM0) for which you are receiving treatment with GnRH agonists to suppress androgen production with a planned duration of further treatment of greater than 4 weeks.

Study details
All participants enrolled in this trial will be randomly allocated (by chance) to one of three groups. The first group will receive 0.9mg per day of estradiol, the second group will receive 1.8mg per day of estradiol, and the third group will receive a placebo (sham) treatment which contains no active ingredient. All three treatments are given as a gel which is rubbed into the skin once per day for 4 weeks.

Researchers will take weekly blood samples from baseline to the end of the 4 week treatment period to determine the impact of each treatment on the level of estradiol in the blood as well as some indicators of bone health and diabetes, and a diary of hot flushes will be completed by all participants.

It is hoped that this trial will provide information on the optimal dose of estradiol to give to men with prostate cancer on ADT, to replace the normal blood (serum) level of estradiol that they would have had were they not taking ADT. A subsequent study will investigate whether this treatment is effective in reducing some of the side effects of ADT.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64382 0
A/Prof Mathis Grossmann
Address 64382 0
University of Melbourne Department of Medicine (Austin Health)
Level 7 Lance Townsend Building
145 Studley Rd
Heidelberg
VIC 3084
Country 64382 0
Australia
Phone 64382 0
+61 3 9496 5000
Fax 64382 0
Email 64382 0
mathisg@unimelb.edu.au
Contact person for public queries
Name 64383 0
Dr Nicholas Russell
Address 64383 0
University of Melbourne Department of Medicine (Austin Health)
Level 7 Lance Townsend Building
145 Studley Rd
Heidelberg
VIC 3084
Country 64383 0
Australia
Phone 64383 0
+61 3 9496 5000
Fax 64383 0
Email 64383 0
nicholas.russell@austin.org.au
Contact person for scientific queries
Name 64384 0
Dr Nicholas Russell
Address 64384 0
University of Melbourne Department of Medicine (Austin Health)
Level 7 Lance Townsend Building
145 Studley Rd
Heidelberg
VIC 3084
Country 64384 0
Australia
Phone 64384 0
+61 3 9496 5000
Fax 64384 0
Email 64384 0
nicholas.russell@austin.org.au

No information has been provided regarding IPD availability
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