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Trial registered on ANZCTR


Registration number
ACTRN12619000807156
Ethics application status
Approved
Date submitted
9/05/2019
Date registered
3/06/2019
Date last updated
12/06/2019
Date data sharing statement initially provided
3/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Clinical Trial to Test a Modified Traditional Chinese Herbal Medicine for the Treatment of Endometriosis
Scientific title
A placebo controlled, double blind, randomised controlled trial to evaluate the treatment efficacy of a modified Gui Zhi Fu Ling Wan formulation (GynoclearTM) in women with endometriosis
Secondary ID [1] 298198 0
None
Universal Trial Number (UTN)
U1111-1233-4407
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 312787 0
Condition category
Condition code
Alternative and Complementary Medicine 311282 311282 0 0
Herbal remedies
Reproductive Health and Childbirth 311442 311442 0 0
Other reproductive health and childbirth disorders
Renal and Urogenital 311443 311443 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product/Therapy: Six (6) capsules of Gynoclear™ taken orally per day for 12 weeks. Dosing schedule will be three (3) capsules in the morning with food and three (3) capsules in the evening, with the evening meal if possible.

Gynoclear™ contains the following active ingredients: cinnamon (92 mg/cap), poria (92 mg/cap), safflower (92 mg/cap), tree peony (92 mg/cap), peony (92 mg/cap) and red sage (92 mg/cap).

Compliance to dosing regime will be monitored through study drug reconciliation at Midpoint (Week 6) and at End of Treatment (Week 12).
Intervention code [1] 314434 0
Treatment: Other
Comparator / control treatment
Women will be randomly allocated in a 1:1 ratio to active (GynoclearTM) or placebo capsules.

Placebo control: Six capsules of colour, smell and taste matched placebo per day for 12 weeks, taken as three capsules orally with food.

Excipient ingredients of placebo: coca powder (20 mg/cap), cellulose microcrystalline (376 mg/cap) and magnesium stearate (4 mg/cap).
Control group
Placebo

Outcomes
Primary outcome [1] 320027 0
To evaluate the efficacy of Gynoclear™ by change in endometriosis related pain based on the Endometriosis pain daily diary (EPDD) scores.
Timepoint [1] 320027 0
Baseline, midpoint (week 6), end of treatment (week 12; primary endpoint) and post-intervention (week 16)
Secondary outcome [1] 370295 0
Composite: To assess the change in health-related quality of life via the Endometriosis Health Profile (EHP-30), SF-12 and EQ5D scores.
Timepoint [1] 370295 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [2] 370296 0
To assess any changes in rescue analgesic usage via the EPDD.
Timepoint [2] 370296 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [3] 370297 0
To assess any changes in dyspareunia (painful sexual intercourse) via the EPDD.
Timepoint [3] 370297 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [4] 370298 0
Composite: To assess any changes in fatigue via the EPDD and fatigue severity scale (FSS).
Timepoint [4] 370298 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [5] 370299 0
To assess any changes in restrictions to activities of daily living (ADLs) via the EPDD.
Timepoint [5] 370299 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [6] 370300 0
To monitor the frequency and severity of adverse events during intervention period.

The expected adverse event profile of Gynoclear is a combination of adverse events reported for its components, namely: rash or allergic skin reactions and gastrointestinal discomfort. Side effects reported in previous clinical trials also include drowsiness, dizziness and thrombocytopenia, however, it is not known if these effects were due to the ingredient, Salvia Miltiorrhiza (Red Sage), that was tested or other drugs. The expected rate for each of these adverse events is infrequent and the expected severity is mild to moderate. Gynoclear is considered relatively safe with no drug related serious adverse events expected at the prescribed dose. There is case of hypoglycemic seizure reported for a patient using cassia cinnamon, but it is unclear if cassia cinnamon caused this event. There is also some concern that cassia cinnamon may cause liver damage due to its coumarin content. However, most evidence suggests that the amount of coumarin in cassia cinnamon is too little to cause adverse effects in most patients.

Adverse events will be graded by the investigator according to NCI CTCAE v4.0. A copy of the CTCAE Version 4.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov/reporting/ctc.html).
Timepoint [6] 370300 0
Intervention period
Secondary outcome [7] 370301 0
To determine the cost-effectiveness of using Gynoclear™ via tools such as MBS/PBS, estimating quality-adjusted years (QALs), Probabilistic Sensitivity Analysis (PSA) and difference of economic measure of HRQoL will be cross-validated using SF12, and a Value of Information (VOI) analysis.
Timepoint [7] 370301 0
Baseline, 3 months (intervention period) and 1 month post-intervention.
Secondary outcome [8] 370302 0
To explore participant satisfaction with the intervention via a questionnaire to be completed electronically by the participant.

At trial entry, participants will be asked about their current symptoms, and what expectations they have regarding any changes in these during the trial.

At the trial exit, participants will be asked to rate their satisfaction with the treatment given, what (if any) symptoms changed, and what impact this had on them. Additional questions will include the likelihood of recommendation of the intervention to family and friends, interest in using the intervention again for pelvic pain symptoms, and feedback on the trial design and outcomes collected.

Both the trial entry and trial exit questionnaires were designed by the authors of the study.
Timepoint [8] 370302 0
End of treatment: after completing 3 months of the treatment period and before the 1 month post intervention follow up.

Eligibility
Key inclusion criteria
- Laparoscopic visualisation/confirmation of endometriosis in the last five years.

- Have menstrual or non-menstrual pelvic pain rated greater than or equal to 4/10 on a numeric rating scale based off an average over one month via Endometriosis pain daily diary v3 scores.

- Report at least ONE of the following:
o Dysmenorrhea (period pain),
o Dyspareunia (pain during or after sexual intercourse),
o Dyschezia (pain before or during bowel motion) OR
o Dysuria (pain prior to or during urination).

- Willing to provide informed consent and adhere to the protocol.

- Able to travel to a Laverty Pathology collection centre for two blood tests.

- If sexually active, agreeing to use appropriate contraception to prevent pregnancy during the study period.

- Has internet access (either via a mobile, tablet or computer) for completing the Endometriosis Pain Daily Diary v3 scores.
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have had endometriosis related surgery in the previous six months.

- Started the oral or injectable contraceptive pill, GnRH-a or danazol within the last six months.

- Started, stopped or changed dosage on any pharmaceutical medication or herbal/natural medicine targeting endometriosis symptoms (such as pregabalin, Nortriptyline, or other Chinese herbal medicine) in the previous six months.

- Having a known allergy or intolerance to any of the ingredients in Gynoclear™.

- Usage of anticoagulants (e.g. Warfarin, Heparin, Eliquis, Pradaxa, Xarelto) or any other medication, including supplements (e.g., Vitamin E, Gingko), that causes blood thinning.

- History of coagulation disorders.

- Currently pregnant or breast feeding or planning on becoming pregnant during the study period.

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
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 302741 0
Commercial sector/Industry
Name [1] 302741 0
Metagenics (Aust) Pty Ltd
Address [1] 302741 0
741 Nudgee Road,
Northgate,
QLD, 4013
Country [1] 302741 0
Australia
Funding source category [2] 302743 0
University
Name [2] 302743 0
Western Sydney University
Address [2] 302743 0
Locked Bag 1797
PENRITH NSW 2751
Country [2] 302743 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Metagenics (Aust) Pty Ltd
Address
741 Nudgee Road,
Northgate,
QLD, 4013
Country
Australia
Secondary sponsor category [1] 302674 0
University
Name [1] 302674 0
Western Sydney University
Address [1] 302674 0
Locked Bag 1797
PENRITH NSW 2751
Country [1] 302674 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303342 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [1] 303342 0
Human Ethics Officer
Research Engagement, Development and Innovation (REDI)
Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Ethics committee country [1] 303342 0
Australia
Date submitted for ethics approval [1] 303342 0
03/05/2019
Approval date [1] 303342 0
28/05/2019
Ethics approval number [1] 303342 0
H13256

Summary
Brief summary
To examine the efficacy and cost-effectiveness of a modified traditional Chinese medicine formula (GynoclearTM) as a treatment for endometriosis related pain and fatigue. The project will utilise a placebo controlled, double blind, randomised controlled trial involving reproductive aged women surgically diagnosed with endometriosis. Baseline scores for pelvic pain, fatigue, painful intercourse (dysparunia) and rescue medication will be collected over four weeks. Women will be randomly allocated in a 1:1 ratio to active (GynoclearTM) or placebo capsules. Six capules will be taken daily for three months. The primary outcome is change in daily pelvic pain score at the end of the intervention. Safety and adverse event data will be collected during the trial and at a one month follow up period. If GynoclearTM shows evidence of efficacy and safety it will be another possible treatment option for the over 360,000 Australian women with endometriosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93342 0
Dr Mike Armour
Address 93342 0
NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751
Country 93342 0
Australia
Phone 93342 0
+61 2 9685 4720
Fax 93342 0
Email 93342 0
M.Armour@westernsydney.edu.au
Contact person for public queries
Name 93343 0
Mr Mahmoud Al-Dabbas
Address 93343 0
NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751
Country 93343 0
Australia
Phone 93343 0
+61 2 9685 4736
Fax 93343 0
Email 93343 0
m.al-dabbas@westernsydney.edu.au
Contact person for scientific queries
Name 93344 0
Dr Mike Armour
Address 93344 0
NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751
Country 93344 0
Australia
Phone 93344 0
+61 2 9685 4720
Fax 93344 0
Email 93344 0
M.Armour@westernsydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results