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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

9/10/2023

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]

None

Universal Trial Number (UTN)

U1111-1233-4407

Trial acronym

Linked study record

Health condition

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

Endometriosis

Condition category

Condition code

Alternative and Complementary Medicine

Herbal remedies

Reproductive Health and Childbirth

Other reproductive health and childbirth disorders

Renal and Urogenital

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]

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]

To evaluate the efficacy of Gynoclear™ by change in endometriosis related pain based on the Endometriosis pain daily diary (EPDD) scores.

Timepoint [1]

Baseline, midpoint (week 6), end of treatment (week 12; primary endpoint) and post-intervention (week 16)

Secondary outcome [1]

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]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [2]

To assess any changes in rescue analgesic usage via the EPDD.

Timepoint [2]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [3]

To assess any changes in dyspareunia (painful sexual intercourse) via the EPDD.

Timepoint [3]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [4]

Composite: To assess any changes in fatigue via the EPDD and fatigue severity scale (FSS).

Timepoint [4]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [5]

To assess any changes in restrictions to activities of daily living (ADLs) via the EPDD.

Timepoint [5]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [6]

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]

Intervention period

Secondary outcome [7]

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]

Baseline, 3 months (intervention period) and 1 month post-intervention.

Secondary outcome [8]

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]

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 2.5/10 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

Sex

Females

Can healthy volunteers participate?

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 three 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 three 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)

Central randomisation via Castor EDC

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation numbers were allocated in permuted blocks of 6 containing 3 active and 3 placebo randomisation numbers. The randomisation sequence using a block size of 6, with 1:1 group allocation, was performed on the 15th of January 2019 by NICMs Clinical Trial Manager who is external to this study.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Not Applicable

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

3/06/2019

Actual

11/06/2019

Date of last participant enrolment

Anticipated

28/02/2021

Actual

26/02/2023

Date of last data collection

Anticipated

31/08/2021

Actual

28/08/2023

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]

Commercial sector/Industry

Name [1]

Metagenics (Aust) Pty Ltd

Address [1]

741 Nudgee Road,
Northgate,
QLD, 4013

Country [1]

Australia

Funding source category [2]

University

Name [2]

Western Sydney University

Address [2]

Locked Bag 1797
PENRITH NSW 2751

Country [2]

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]

University

Name [1]

Western Sydney University

Address [1]

Locked Bag 1797
PENRITH NSW 2751

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Western Sydney University Human Research Ethics Committee

Ethics committee address [1]

Human Ethics Officer
Research Engagement, Development and Innovation (REDI)
Western Sydney University
Locked Bag 1797
Penrith NSW 2751

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/05/2019

Approval date [1]

28/05/2019

Ethics approval number [1]

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

A/Prof Mike Armour

Address

NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751

Country

Australia

Phone

+61 2 9685 4720

Fax

[email protected]

Contact person for public queries

Name

Mike Armour

Address

NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751

Country

Australia

Phone

+61 2 9685 4736

Fax

[email protected]

Contact person for scientific queries

Name

Mike Armour

Address

NICM Health Research Institute
Western Sydney University
Building J, Westmead Campus
Locked Bag 1797
PENRITH NSW 2751

Country

Australia

Phone

+61 2 9685 4720

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
20631	Study protocol	Armour, M.; Al-Dabbas, M.A.; Ee, C.; Smith, C.A.; Ussher, J.; Arentz, S.; Lawson, K.; Abbott, J. The effectiveness of a modified Gui Zhi Fu Ling Wan formulation (Gynoclear™) for the treatment of endometriosis: a study protocol for a placebo-controlled, double-blind, randomised controlled trial. Trials 2021, 22, 299, doi:10.1186/s13063-021-05265-x.	https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05265-x

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	The effectiveness of a modified Gui Zhi Fu Ling Wan formulation (GynoclearTM) for the treatment of endometriosis: a study protocol for a placebo-controlled, double-blind, randomised controlled trial.	2021	https://dx.doi.org/10.1186/s13063-021-05265-x

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

Trial Review

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