The MarVeL Study may be suitable for you if you:

- Are aged 40 years or over,

- Are able to attend study visits at the following locations over the 6-month study period:

Royal North Shore Hospital for up to 6 visits including a study knee X-ray and an ultrasound at Castlereagh Imaging (St Leonards)

Castlereagh Imaging (Cremorne) for 2 knee MRI scans, at the start and end of the study

- Have had knee pain on most days for the past six months or longer

- Have no contraindications for an MRI

- Are not being currently treated for haemophilia

- Do not have a history of gastrointestinal bleeding

- Are not currently taking heparin or other oral anticoagulant medications

- Are not taking steroid medications

- Have not received a corticosteroid injection in the past 3 months

- Have not received Hyaluronic, PRP or regenerative (stem cell) medicine injections in the past 6 months or an arthroscopy to your most painful knee in the past 12 months

- Are not currently taking statins for lowering cholesterol

- Are willing to stop tasking NSAIDs during the study

- Have internet access and a mobile device/laptop for completing online surveys

If you are interested in joining the study, first you will need to complete the online screening survey. The online screening survey will assess if the study might suit you.

After you submit the online screening survey and you are potentially eligible, a member of the study team will be in contact with you to clarify any of your answers if necessary and explain the next steps of the screening process.

If you are eligible for the study, you will be randomly allocated to either the active group of the placebo group:

Active group: will receive Pentosan Polysulfate Sodium (PPS) capsules

Placebo group: will receive placebo capsules without the active ingredient

TGA-approved PPS capsules will be taken for two 5-week treatment periods.

The MaRVeL Study is a double-blinded study meaning you and the researchers will not know which group you have been allocated to until after your participation in the study is finished.

Over 6-months, we anticipate that your total time commitment for the study will be approximately 12 hours spread across six study visits and periodic online surveys.

During the online screening period, you will be required to complete the online screening survey, a knee x-ray at Castlereagh Imaging Centre (St Leonards), and a (fasting) blood test.

If you are eligible for the study, over the 6-month study period you will be required to attend:

• Royal North Shore Hospital: 4 times

• Castlereagh Imaging in St Leonards for an index knee ultrasound examination: 1 time

• Castlereagh Imaging in Cremorne for an index knee MRI examination: 2 times

You will not pay for any treatment or procedures done in this study. All imaging services and pathology tests will be free of cost to you. We will provide you with a complimentary Royal North Shore Hospital meal and parking vouchers.

If you are interested in joining the study, please complete the online screening survey by clicking the green button below. The survey consists of approximately 40 short questions and will take about 10-15 mins to complete.

You can pause the survey at any time and return later by clicking ‘save’. Please take note of the ‘Return Code’ that will display on the screen as you will need this to return to the survey. You will automatically be sent an email with a link to the survey. Once you are ready to continue, please follow the link, and enter your code.

After you submit the online screening survey and are potentially eligible, study staff will be in contact with you to clarify any of your answers if necessary and explain the next steps of the screening process which involves a x-ray of both knees and fasting blood test.

If you have questions now or at any point during the screening process or study, please send an email to:

marvel.study@sydney.edu.au