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Trial registered on ANZCTR


Registration number
ACTRN12625001098426
Ethics application status
Approved
Date submitted
18/09/2025
Date registered
8/10/2025
Date last updated
8/10/2025
Date data sharing statement initially provided
8/10/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
Microvascular Modulation in Endometriosis (MMEND) Study: Efficacy of Garlic Extract and L-Arginine in Reducing Endometrial Pain Burden
Scientific title
Microvascular Modulation in Endometriosis (MMEND) Study:
A Double-Blind Evaluation of Garlic Extract and L-Arginine Effect on Endometrial Pain Burden
Secondary ID [1] 315407 0
Nil
Universal Trial Number (UTN)
U1111-1323-3297
Trial acronym
MMEND (Microvascular Modulation in Endometriosis)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 338912 0
Condition category
Condition code
Inflammatory and Immune System 335210 335210 0 0
Other inflammatory or immune system disorders
Diet and Nutrition 335211 335211 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 335285 335285 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A phase-II, randomised, double-blind, two-arm, 48-week study (plus 8-week screening) will be conducted in individuals with medically confirmed endometriosis. This study aims to evaluate the effects of garlic extract alone or in combination with L-arginine on endometriosis associated pain, quality of life and inflammatory and angiogenic biomarkers. Each participant will be randomised into the 2 arms and self-administer the allocated nutraceuticals.

Arm 1: Garlic Extracts (oral capsule)
Arm 2: Garlic Extracts + L-arginine or Placebo (oral capsule)

The intervention will be provided as follows:
- Phase 1: Weeks 0–16: All receive 200 mg Garlic Extract daily.
- Phase 2: Weeks 17–32: Continue Garlic Extract + randomised to either 1500 mg L-arginine or placebo daily.
- Follow up: Weeks 33–48: 16-week follow-up period. No intervention, follow-up assessments continue.
Capsule counts will be conducted at study visits to ensure adequate adherence to intervention protocol.
Intervention code [1] 332015 0
Treatment: Other
Comparator / control treatment
There is no placebo for the first phase of the intervention however, the introduction of the second nutraceutical will be double blinded (to both participants and investigators) and have a matched placebo. This approach ensures that all participants receive an active intervention while maintaining methodological rigor in assessing the effects of the second nutraceutical. The placebo contains microcellulose (insoluble fibre) and will be identical to L-arginine in appearance.
Control group
Placebo

Outcomes
Primary outcome [1] 342820 0
To measure the effects of 200mg Garlic Extract alone or in combination with 1500mg of L-arginine on visual analogue pain scores endometriosis associated pain severity.
Timepoint [1] 342820 0
Participants will record the severity worst endometriosis associated pain experienced in the past 7 days, weekly throughout the entire trial period (including baseline and follow up period).
Primary outcome [2] 342821 0
To measure the effects of 200mg Garlic Extract alone or in combination with 1500mg of L-arginine on quality of life for individuals with endometriosis.
Timepoint [2] 342821 0
This questionnaire will be completed at 4 points throughout the study (baseline, after intervention phase 1, after intervention phase 2 and follow up).
Primary outcome [3] 342927 0
To measure the effects of 200mg Garlic Extract alone or in combination with 1500mg of L-arginine on visual analogue pain scores endometriosis associated pain severity.
Timepoint [3] 342927 0
Participants will record the severity worst endometriosis associated pain experienced in the past 7 days, weekly throughout the entire trial period (including baseline and follow up period).
Secondary outcome [1] 452272 0
To measure the changes in tumour necrosis factor-alpha at baseline, mid intervention and end of intervention (32 week period).
Timepoint [1] 452272 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [2] 452273 0
To measure the changes in Matrix Metalloproteinases at baseline, mid intervention and end of intervention (32 week period).
Timepoint [2] 452273 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [3] 452274 0
To measure the changes in average dysmenorrhea pain through the baseline, intervention and follow up period.
Timepoint [3] 452274 0
The PGA will be completed at baseline, mid intervention, end of intervention and end of follow up period (0, 16, 32, 48 weeks).
Secondary outcome [4] 452275 0
To measure the changes in participant perception of dysmenorrhea pain changes during the intervention and follow up period.
Timepoint [4] 452275 0
The PGIC will be completed at mid intervention, end of intervention and end of follow up period (16, 32, 48 weeks).
Secondary outcome [5] 452738 0
This is an additional primary outcome: To measure the effects of 200mg Garlic Extract alone or in combination with 1500mg of L-arginine on visual analogue pain scores endometriosis associated pain severity.
Timepoint [5] 452738 0
Participants will record the severity worst endometriosis associated pain experienced in the past 7 days, weekly throughout the entire trial period (including baseline and follow up period).
Secondary outcome [6] 452740 0
This is an additional primary outcome: To measure the effects of 200mg Garlic Extract alone or in combination with 1500mg of L-arginine on visual analogue pain scores endometriosis associated pain severity.
Timepoint [6] 452740 0
Participants will record the severity worst endometriosis associated pain experienced in the past 7 days, weekly throughout the entire trial period (including baseline and follow up period).
Secondary outcome [7] 452744 0
To measure the changes in interlukin-1beta at baseline, mid intervention and end of intervention (32 week period).
Timepoint [7] 452744 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [8] 452745 0
To measure the changes in c-reactive protein at baseline, mid intervention and end of intervention (32 week period).
Timepoint [8] 452745 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [9] 452746 0
To measure the changes in prostaglandin e2 at baseline, mid intervention and end of intervention (32 week period).
Timepoint [9] 452746 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [10] 452749 0
To measure the changes in hypoxia inducible factor 1 alpha at baseline, mid intervention and end of intervention (32 week period).
Timepoint [10] 452749 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [11] 452750 0
To measure the changes in Vascular Endothelial Growth Factor at baseline, mid intervention and end of intervention (32 week period).
Timepoint [11] 452750 0
Blood samples will be collected at baseline, 16 and 32 weeks post baseline.
Secondary outcome [12] 452751 0
To measure the changes in average dyspareunia pain through the baseline, intervention and follow up period.
Timepoint [12] 452751 0
The PGA will be completed at baseline, mid intervention, end of intervention and end of follow up period (0, 16, 32, 48 weeks).
Secondary outcome [13] 452752 0
To measure the changes in average non-menstrual pelvic pain through the baseline, intervention and follow up period.
Timepoint [13] 452752 0
The PGA will be completed at baseline, mid intervention, end of intervention and end of follow up period (0, 16, 32, 48 weeks).
Secondary outcome [14] 452753 0
To measure the changes in average back pain through the baseline, intervention and follow up period.
Timepoint [14] 452753 0
The PGA will be completed at baseline, mid intervention, end of intervention and end of follow up period (0, 16, 32, 48 weeks).
Secondary outcome [15] 452754 0
To measure the changes in participant perception of dyspareunia changes during the intervention and follow up period.
Timepoint [15] 452754 0
The PGIC will be completed at mid intervention, end of intervention and end of follow up period (16, 32, 48 weeks).
Secondary outcome [16] 452755 0
To measure the changes in participant perception of non-menstrual pelvic pain changes during the intervention and follow up period.
Timepoint [16] 452755 0
The PGIC will be completed at mid intervention, end of intervention and end of follow up period (16, 32, 48 weeks).
Secondary outcome [17] 452756 0
To measure the changes in participant perception of back pain changes during the intervention and follow up period.
Timepoint [17] 452756 0
The PGIC will be completed at mid intervention, end of intervention and end of follow up period (16, 32, 48 weeks).

Eligibility
Key inclusion criteria
1. Participant provided written, informed consent.
2. Medically confirmed diagnosis of endometriosis via laparoscopy (with or without histological confirmation), magnetic resonance imaging (MRI) or ultrasound imaging
3. Moderate to severe endometriosis-associated pain, scoring 4 or greater on visual analogue scale (VAS).
4. During the baseline period a mean pain score of 4 or greater for at least one VAS pain domain.
5. Pelvic pain that has occurred for longer than 6 months.
6. Premenopausal female, aged 18-45 years old (inclusive) at screening.
7. Able to commit to taking oral capsules once a day for 32 weeks.
8. Able to complete electronic weekly pain questionnaire over 56 weeks.
9. Have access to the internet to complete electronic questionnaires.
10. If sexually active, participant can commit to using appropriate contraception (condoms, IUD, continued oral contraception).
11. Be willing to and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy (or planning to be pregnant within the study period) or breastfeeding.
2. Surgery related to endometriosis within 6 months of screening period.
3. Any surgery planned during study period (56 weeks).
4. Chronic pelvic pain that, in the opinion of the investigator, was not caused by endometriosis and required chronic analgesic use or other chronic therapy, or that interfered with the assessment of endometriosis-related pain.
5. The participant had any known condition, which in the opinion of the investigator constituted a risk or contraindication to participating in the study, or that could interfere with the study objectives, implementation or evaluation.
6. Clinical reports of kidney/liver dysfunction.
7. Unknown genital bleeding.
8. L-arginine tablets or garlic extract tablets in previous 3 months prior to screening.
9. Adverse reactions to food containing L-arginine or garlic.
10. Known risks of bleeding or coagulopathy or currently on blood-thinning medications.
11. Use of anticoagulants or any other medication (including supplements) that causes blood thinning.
12. Current diagnosis of cancer (with exception to cancers of the skin), haemochromatosis or diabetes.
13. History of diabetes, hypertension, hypotension, collagen vascular disease, vasculitis or renal disease/failure.
14. Acute/chronic pain disorders, infections, cardiovascular or cerebrovascular disease.
15. Evidence of significant unmanaged mood or anxiety-related symptoms, at the discretion of the investigator.
16. History of substance abuse/dependence/addiction.
17. Smoke >1 pack of cigarettes a day.
18. Changes (started, stopped or changed dosage) to hormonal contraception within 3 months of screening.
19. Changes (started, stopped or changed the dosage) on any pharmaceutical medication or herbal/natural medicine targeting endometriosis symptoms in the previous 3 months of screening.
20. Participation in concurrent research trial.

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)
An external researcher/statistician will assign participants to intervention group and will be the only person who has access to this list.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible participants will be randomised by block randomisation with a block size of 6, via computer generated sequences.
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
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed via statistics software SPSS V29.0.2.0 (SPSS Inc., Chicago, III, USA), through an intention to treat analysis to ensure results capture realistic intervention adherence and effects. All results will be presented as group mean ± standard deviation. Normality will be assessed through Kolmogorov-Smirnov Test and the Shapiro-Wilk Test. To compare both intervention groups, average pain scores (from each domain from the VAS and impression of change) and concentrations of biomarkers will be analysed through an independent-samples t-test. For group differences of QoL the non-parametric test, Mann-Whitney U test will be implemented. Wilcox signed rank test will be implemented to compare outcome measures between baseline and end of study. All demographic data collected will be reported using Chi square test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
25/09/2025
Date of last participant enrolment
Anticipated
4/05/2026
Actual
Date of last data collection
Anticipated
7/06/2027
Actual
Sample size
Target
150
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 319480 0
Charities/Societies/Foundations
Name [1] 319480 0
Philanthropic donations
Country [1] 319480 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Country
Australia
Secondary sponsor category [1] 322533 0
None
Name [1] 322533 0
None
Address [1] 322533 0
Country [1] 322533 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318052 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 318052 0
Ethics committee country [1] 318052 0
Australia
Date submitted for ethics approval [1] 318052 0
20/05/2025
Approval date [1] 318052 0
18/06/2025
Ethics approval number [1] 318052 0
HRE2025-0324

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142966 0
Prof John Mamo
Address 142966 0
Curtin University, Kent Street, Bentley WA 6102
Country 142966 0
Australia
Phone 142966 0
+61 08 9266 7232
Fax 142966 0
Email 142966 0
[email protected]
Contact person for public queries
Name 142967 0
Professor John Mamo
Address 142967 0
Curtin University, Kent Street, Bentley WA 6102
Country 142967 0
Australia
Phone 142967 0
+61 08 9266 7232
Fax 142967 0
Email 142967 0
[email protected]
Contact person for scientific queries
Name 142968 0
Professor John Mamo
Address 142968 0
Curtin University, Kent Street, Bentley WA 6102
Country 142968 0
Australia
Phone 142968 0
+61 08 9266 7232
Fax 142968 0
Email 142968 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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
No additional documents have been identified.