Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000185369
Ethics application status
Approved
Date submitted
31/01/2017
Date registered
3/02/2017
Date last updated
3/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Metabolic effects of cross-sex hormone treatment
Scientific title
Metabolic effects of cross-sex hormone treatment in transgender individuals
Secondary ID [1] 291032 0
None
Universal Trial Number (UTN)
U1111-1192-2161
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic Health 301821 0
Condition category
Condition code
Metabolic and Endocrine 301500 301500 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
12
Target follow-up type
Months
Description of intervention(s) / exposure
Potential participants will be invited to the study if they are scheduled to commence male-to-female (feminising) or female-to-male (masculinising) cross-sex hormone treatment. Cross-sex hormones are used to facilitate the gender affirmation process in transgender individuals. Feminising therapy initially begins with administration of androgen blockers, with oestrodiol (oral or transdermal) added after 6 - 12 weeks, with the dose titrated to maximal dose or until biochemical targets are met. Masculinisng therapy involves adminstration of transdermal testosterone, beginning at 1/4 dose on alternating days and titrated up over 8-12 weeks until maximal dose is reached. After biochemical treatments are met, transition to injectable testosterone treatment may be considered. Treatments are individualised and may vary according to individual response.
Study appointments will be before commencing treatment (baseline), 3 months, 6 months and 12 months. Each appointment will take 40-60 minutes to complete, and will be scheduled alongside the routine appointments with the Endocrinologist, At each time-point routine clinical measurements will be recorded (fasting glucose, blood lipid profile, FBC, LFT, & UEC ). In addition to these, the following outcomes will be measured: Body composition using biometric impedance analysis and dual-energy xray absorpiometry (DEXA); dietary intake, physical activity, and self-perceived health & wellbeing will be measured using questionnaires; and a small blood sample will be collected to measure fasting insulin, erythrocyte and plasma fatty acid profile, adipokines and inflammatory markers.
Intervention code [1] 297004 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300892 0
Change in eicosapentaenoic acid and docosahexaenoic acid content of erythrocyte membranes, measured using gas chromatography from a fasted blood sample
Timepoint [1] 300892 0
0, 3, 6, & 12 months
Secondary outcome [1] 331132 0
Anthropometric measurements
Height (baseline only), weight, waist circumference, hip circumference
Timepoint [1] 331132 0
0, 3, 6 & 12 months
Secondary outcome [2] 331133 0
Body fat distribution, measured using biometric impedance analysis and dual x-ray absorpiometry (DEXA)
Timepoint [2] 331133 0
0, 3, 6 & 12 months
Secondary outcome [3] 331134 0
Insulin Resistance, as measured by HOMA-IR (fasting glucose x fasting insulin / 22.5), measured by commercial pathology using standardized techniques.
Timepoint [3] 331134 0
0, 3, 6, & 12 months
Secondary outcome [4] 331135 0
Plasma Inflammatory Markers (IL-6, TNF-alpha), measured using ELISA assays
Timepoint [4] 331135 0
0, 3, 6, & 12 months
Secondary outcome [5] 331136 0
Routine clinical measurements of metabolic health (LFT, FBC, UEC, blood lipid profile [total cholesterol, LDL-cholesterol, HDL-cholesterol, fasting triglycerides, fasting glucose, & HbA1c), measured by hospital pathology services using standardized methods
Timepoint [5] 331136 0
0, 3, 6, & 12 months
Secondary outcome [6] 331180 0
Dietary Intake, measured using a validated online food frequency questionnaire (Australian Eating Survey)
Timepoint [6] 331180 0
0, 3, 6, & 12 months
Secondary outcome [7] 331182 0
Self-perceived health and well-being, measured using self-administered questionnaire (SF-36)
Timepoint [7] 331182 0
0, 3, 6, & 12 months
Secondary outcome [8] 331183 0
Physical Activity, measured using a validated self-administered questionnaire (International Physical Activity Questionnaire, long version)
Timepoint [8] 331183 0
0, 3, 6, & 12 months
Secondary outcome [9] 331184 0
Fasting serum insulin, measured by commercial pathology using standardized methods
Timepoint [9] 331184 0
0, 3, 6, & 12 months
Secondary outcome [10] 331185 0
Plasma adipokines (adiponectin, leptin), measured using ELISA assays
Timepoint [10] 331185 0
0, 3, 6, & 12 months
Secondary outcome [11] 331186 0
Change in plasma eicosapentaenoic acid (EPA) and docoshexaenoic acid (DHA) levels, measured using gas chromatography from a fasted blood sample
Timepoint [11] 331186 0
0, 3. 6, & 12 months

Eligibility
Key inclusion criteria
Participants will be invited to join the study if they are:
- Aged 18 years or older
- Commencing cross-sex hormone treatment at John Hunter Hospital
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The following people will be excluded from volunteering from the study:
- Children and young people less than 18 years
- People who regularly consume more than 2 serves / week (250g) oily fish or taking fish oil capsules
- People with an intellectual or mental impairment who cannot give informed consent

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample Size: A 23% increase in Omega-3 Index (%EPA+DHA content of erythrocyte membranes) has been determined to reduce the risk of sudden cardiac death by approximately 50%. Previous studies in transgender individuals and early pregnancy have reported changes to plasma DHA levels, with no changes to EPA levels . Eighteen people in each group will give 80% power to detect a 20% change in DHA content of erythrocyte membranes, assuming a standard deviation in the response to treatment to be 30%, with alpha set at p=0.05. In order to account for withdrawals we will recruit 20 participants from each group (i.e. 20 trans-males and 20 trans-females).
Treatment effects: All the data will be tested for normality and expressed as mean +/- SEM or median (IQR) as appropriate. The effect of CSH on outcome measures will be determined using paired t-tests. Alpha will be set at p=0.05. Significance (P-value set at 0.05) indicates the changes from the baseline values. Changes from the baselines over all time-points will be determined using one-way ANOVA using repeated measures.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/02/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7397 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15195 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295458 0
University
Name [1] 295458 0
University of Newcastle
Country [1] 295458 0
Australia
Funding source category [2] 295476 0
Charities/Societies/Foundations
Name [2] 295476 0
Hunter Medical Research Institute
Country [2] 295476 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive,
Callaghan, NSW, 2308
Country
Australia
Secondary sponsor category [1] 294282 0
None
Name [1] 294282 0
Address [1] 294282 0
Country [1] 294282 0
Other collaborator category [1] 279411 0
Hospital
Name [1] 279411 0
John Hunter Hospital
Address [1] 279411 0
Locked Bag 1
New Lambton
NSW, 2305
Country [1] 279411 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296791 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 296791 0
Locked Bag 1
New Lambton, NSW, 2305
Ethics committee country [1] 296791 0
Australia
Date submitted for ethics approval [1] 296791 0
30/11/2016
Approval date [1] 296791 0
21/12/2016
Ethics approval number [1] 296791 0
2016/12/14/4.03
Ethics committee name [2] 296792 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 296792 0
Human Research Ethics Officer
Research Office,
The Chancellery,
The University of Newcastle
University Drive,
Callaghan, NSW, 2308
Ethics committee country [2] 296792 0
Australia
Date submitted for ethics approval [2] 296792 0
09/01/2017
Approval date [2] 296792 0
13/01/2017
Ethics approval number [2] 296792 0
H-2017-0011

Summary
Brief summary
Biological differences between males and females are well known in terms of reproductive functioning. However, it is becoming increasingly well recognised that non-communicable chronic diseases, such as diabetes, cardiovascular disease, and many neurological and mental health disorders display sexual dimorphisms in their pathogenesis and presentation. Females are somewhat protected against both the development of insulin resistance and cardiovascular disease compared with males of a similar age. However, this difference between sexes diminishes after women reach menopause. Much of this sexual dimorphism has been attributed to the regulatory effects of the steroid sex hormones testosterone, oestrogen and progesterone.
Cross-sex hormones (CSH) are a treatment option used to treat gender dysphoria (DSM V) and facilitate transition from their natal sex (i.e. sex assigned at birth) to their identified gender. Feminisation typically requires administration of androgen-blockers and co-administration of oestrogen hormones, whereas masculinisation requires administration of testosterone treatment. Treatment with CSH is usually lifelong.
Evidence shows that transgender persons are at an increased risk of mental distress and chronic disease. In addition to the physical changes induced by cross-sex hormone therapy commonly associated with puberty (such as changes to body hair, skin appearance), cross-sex hormones have been shown to influence factors such as body composition. The overall effect of cross-sex hormone treatment on cardiovascular and diabetes risk is still unclear. Cross-sex hormone treatment has been reported to both improve and impair various CVD risk factors, such as fasting glucose and insulin levels, plasma docosahexaenoic acid (DHA) levels, adipokines and C-reactive protein.
Studying the effect of cross-sex hormones on DHA status and other risk factors for CVD and diabetes in transgender persons undergoing hormone therapy allows a unique opportunity to investigate the contribution of sex hormones to the sexual dimorphisms apparent in both these conditions. Furthermore, investigating metabolic changes in response to cross-sex hormone treatment may help to inform dietary and/or pharmaceutical strategies for minimizing the health risks associated with receiving CSH in this at risk group. Therefore the aim of this observational study is to measure the effect of cross-sex hormone therapy on metabolic risk factors for both diabetes and CVD in transgender individuals undergoing hormone therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72066 0
Dr Katie-Jane Wynne
Address 72066 0
John Hunter Hospital
Locked Bag 1
New Lambton, NSW, 2305
Country 72066 0
Australia
Phone 72066 0
+61 2 49213000
Fax 72066 0
Email 72066 0
[email protected]
Contact person for public queries
Name 72067 0
Ms Kylie Abbott
Address 72067 0
305B Medical Sciences Building
University of Newcastle
University Drive,
Callaghan, NSW, 2308
Country 72067 0
Australia
Phone 72067 0
+61 2 49215638
Fax 72067 0
Email 72067 0
[email protected]
Contact person for scientific queries
Name 72068 0
Ms Kylie Abbott
Address 72068 0
305B Medical Sciences Building
University of Newcastle
University Drive,
Callaghan, NSW, 2308
Country 72068 0
Australia
Phone 72068 0
+61 2 49215638
Fax 72068 0
Email 72068 0
[email protected]

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Results publications and other study-related documents

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