Information for Participants

Implementation of Metformin theraPy to Ease DEcline of kidney function in Polycystic Kidney Disease (IMPEDE-PKD) Randomised Placebo-Controlled Trial

We are inviting you to take part in a research study. Please read this information which will help you decide. Click each question box to open further information.

Why are we doing this study?

We are doing this study to find out whether a drug called metformin can slow down the rate at which kidney disease progresses in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Metformin is not a new medicine. It is currently used to treat patients with diabetes.

Do I have to take part?

If you do not want to take part that’s OK. Your decision will not affect the care you receive.

If you take part, you are free to withdraw at any time without giving a reason.

What will PART 1 of the study involve?

The study will have two parts – PART 1 and PART 2

PART 1

You will be asked to visit the clinic to do some tests. We will record your weight, waist measurement, blood pressure and heart rate and check your current medications. We also collect a blood and urine test to assess your health, check whether you have diabetes and check your cholesterol level. If you are female of childbearing age, we will also do a pregnancy test. You will need to fast (not eat) for 9-12 hours before this blood test. This visit is to confirm whether it is OK for you to join the study.

Ask you to complete surveys about your quality of life and any gut symptoms. This will take around 15 minutes to complete.

If the tests confirm you are OK to join the study, we will give you metformin to take for 10 weeks and ask you to complete some questionnaires.

You will be asked to come to the clinic 2 more times – after 4 weeks and 8 weeks.

  • At these visits we will take your blood pressure and do a blood test. These visits last about 20-30 minutes.

We will also contact you briefly by phone between your clinic visits. We will check how you are getting on with the metformin and if your other medication has changed. Depending on how you are getting on, we may ask you to change the number of tablets of metformin you take.

After 10 weeks you will stop taking metformin.

If you are unable to tolerate 2 tablets of metformin a day, you will not continue on the study.

If you have been able to tolerate 2 tablets of metformin a day, you will stop taking metformin for 2 weeks. After that time, we will arrange a clinic visit to see whether you can enter PART 2 of the study. During this visit we will:

  • check if your other medications have changed
  • Collect a blood and urine sample to assess your health, check again whether you have diabetes and check your cholesterol level. If you could become pregnant, we will also do a pregnancy test. You will have to fast (not eat) for 9 to 12 hours before the blood test.
  • Collect and store extra blood samples to test how well your kidneys are working and whether the metformin has worked. [Delete if not applicable at the site name].
  • Ask you to complete surveys about your quality of life and any gut symptoms. This will take around 15 minutes to complete.

When your doctor has the results of these tests, they will contact you to let you know whether you are suitable for PART 2 of the study.

What will PART 2 of the study involve?

We will use a process called randomisation to allocate you to a study group. One group will take metformin for 24 months and the other group will take a placebo (an inactive pill) for 24 months. Click here to find out why this study uses randomisation to choose your group.

Neither you nor your doctor will know what medication you are taking.

After 1 month we will telephone you to ask about your medication. This will take 5-10 minutes.

You will visit the clinic after 3 months and then every 6 months. Visits will take about 1 hour.

We will:

  • Record your weight, waist measurement, blood pressure and heart rate and check if your other medications have changed
  • Collect a blood and urine sample to assess your health, check again whether you have diabetes and check your cholesterol level. If you are female of childbearing age, we will also do a pregnancy test. You will have to fast (not eat) for 9-12 hours before the blood test.
  • Ask you to complete surveys about your pain (takes about 5 to 10 minutes to complete)
  • Give you more trial medication (not applicable at 3-month visit)
  • Ask you to return unused trial medication (not applicable at 3-month visit)

At the 12-month and 24-month visits we will also:

  • Test your vitamin B12 level as part of your blood test
  • Ask you to complete surveys about how you feel (quality of life) and your gut symptoms. This will take about an extra 10 minutes to complete. We may ask you to fill out an extra questionnaire if you have any gut symptoms.
  • Collect and store extra blood samples to test how well your kidneys are working. [Delete if not applicable at the site name].

What else do I have to do during the research?

While you are on the study you should:

  • Continue with your normal daily activities throughout the trial.
  • Take tablets with food during your evening meal (this can reduce stomach upsets).
  • Let your doctor know straight away if you become unwell or have concerns.
  • Know which medications to avoid taking while on the study. Your doctor will tell you which medications you should avoid. You can also click here for this list of medications.

What are the benefits of taking part?

You may not benefit from taking part in the study, but if you take part, you will be helping to improve understanding of how to treat patients with ADPKD.

What are the risks of taking part?

All medications may have side effects. The most common side effects people have when they first start taking metformin are – nausea, vomiting, and diarrhea and skin reactions (redness, rash, itching or rash). The effects of metformin on unborn babies are unknown.

A rare, but serious side effect of metformin is lactic acidosis. You should talk to your doctor straight away if you have these symptoms:

– Nausea, vomiting, stomach pain– Sleepiness
– Trouble breathing– Dizziness or light-headedness
– Feeling weak, tired or generally unwell– Shivering, feeling extremely cold
– Unusual muscle pain– Slow heartbeat
What information about me is collected?

To find out whether metformin was effective or not, study researchers will ask your permission to access your Medicare Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS) data so we can collect information on how many health services you use during the study.

Your data will also be linked to other sources of information held by government agencies. This information includes records on hospital admission, hospital visits, the cost of each visit, survival, and use of medications.  Once your data are linked, all personal information (including name, date of birth and address) will be removed. 

The study sponsor (The University of Queensland) will collect, store, and send the above personal details to the Data Linkage office in a safe manner.

Click here to find out more about how your data is used and linked to other data for the research and more about how your privacy and confidentiality are protected.

What will happen to my samples?

During the study, routine blood and urine samples will be taken as part of your normal care. These samples will be tested in your hospital or local pathology lab, then destroyed.

[Delete if not applicable at the site name] Researchers are trying to learn more about ADPKD and how your body reacts to metformin. If you give your consent for the collection of extra blood when routine blood samples are taken, this blood will be frozen and stored for testing later.   

Click here to find out more about this optional study from your blood samples

Who is organising this study?

The study is being led and organised by the University of Queensland. It is funded by a government grant.

Summary of trial activities
More information

More information on Autosomal Dominant Polycystic Kidney Disease (ADPKD): https://pkdaustralia.org

What are the risks or side effects of metformin?
Further information about metformin
Information on complaints, compensation and the ethics committee that approved this study
What if I suffer and injury or complications because of the study?

You should contact the research team as soon as possible and you will be assisted with arranging appropriate medical treatment. If you are eligible for Medicare, you can receive any medical treatment required to treat the injury or complication, free of charge, as a public patient in any Australian public hospital.

Who can help if I have concerns about the study?

For matters relating to research at the site at which you are participating, the details of the local site complaints person are:

Complaints contact person
Name[Name]
Position[Position]
Telephone[Phone number]
Email[Email address]

If you have any complaints about any aspect of the project, the way it is being conducted or any questions about being a research participant in general, then you may contact your local HREC administrator for the requirements at your institution.

Reviewing HREC approving this research and HREC Executive Officer details
Reviewing HREC name Metro South Health Ethics Compliance Team
HREC Executive Officer N/A
Telephone 07 3443 8047
Email MSH-Ethics@health.qld.gov.au
What if I have complaints regarding my MBS/PBS information?

If you have a privacy complaint in relation to the use of your MBS/PBS information you should contact the office of the Australian Information Commissioner:

Websitehttp://www.oaic.gov.au
Telephone1300 363 992
Emailenquiries@oaic.gov.au
MailGPO Box 5218, Sydney NSW 2001
What happens if the trial is stopped unexpectedly and how you will be kept informed if new information arises during the study?
What if new information arises during this study?

Your trial doctor will tell you about any new information and discuss with you whether you want to continue in this research. Your trial doctor might consider it to be in your best interests to withdraw you from this research. If this happens, he/she will explain the reasons and arrange for your regular health care to continue.

Could this study be stopped unexpectedly?

Research projects may be stopped unexpectedly for a variety of reasons such as:

  • Unacceptable side effects
  • The drug being shown not to be effective
  • The drug being shown to work and not need further testing
  • Decisions made by local regulatory/health authorities.

Your doctor will let you know what options you have.

Why does this study use randomisation?

Sometimes we do not know which treatment is best for treating a condition. To find out, we need to compare different treatments. This clinical trial will compare metformin with a placebo. A placebo is a medication with no active ingredients. You will be randomly allocated to either take metformin (the treatment group) or the placebo (the control group) The results from each group will be compared at the end of the trial to see if one is better.

Neither you nor your trial doctor will know which treatment you are receiving. In special circumstances, for example a medical emergency your trial doctor can find out which treatment you are receiving.

This study has been designed to make sure the researchers interpret the results in a fair and appropriate way and avoids trial doctors or participants jumping to conclusions. 

Medications to avoid
How will my information and confidentiality be protected?

By signing the consent form, you consent to the trial doctor and relevant research staff collecting and using personal information about you for the study. Information about you may be obtained from your health records held at this and other health services for the purpose of this research.

Any information obtained in connection with this research that can identify you will remain confidential and stored securely. After enrolment, you will be given a unique ID. The research/trial data will be collected using this ID, not your name or any other identifiable information (e.g., date of birth, hospital UR number). Any information with your name or any other identifiable information is only accessed by the staff involved in this research who have completed training for ensuring confidentiality of research participants.

Your personal and health information collected for this study will be stored beyond the term of this project for both regulatory and potential new research purposes. It is only released to doctors or hospitals involved in your care, or with your consent for future research purposes or where an ethics committee has granted approval for non-identifiable information to be used without your consent as allowed under law. No identifying information is ever released publicly.

Your health records and any information obtained during the study are subject to inspection (for the purpose of verifying the procedures and the data) by the relevant authorities and authorised representatives of the Australasian Kidney Trials Network at the University of Queensland, [Name of institution], or as required by law. By signing the Consent Form, you authorise release of, or access to, this confidential information to the relevant research personnel and regulatory authorities as noted above.

It is anticipated that the results of this study will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission. Reference will be made to the study ID only, not to any identifiable information. 

Information about your participation in this study may be recorded in your health records. In accordance with relevant Australian and/or [Name of state/territory] privacy and other relevant laws, you have the right to request access to your information collected and stored by the research team. You also have the right to request that any information with which you disagree be corrected. Please contact the research team member named at the end of this document if you would like to access your information.

Other information collected

We will collect information on how many health services you use during the study. You are asked to consent for study researchers to access your Medicare Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS) data.

  • MBS collects information on medical visits, tests and procedures
  • PBS collects information on prescription medicines.

At the end of the study, the researchers will request your data from Services Australia. To collect your MBS and PBS information, your personal information (Medicare card number, name, date of birth, sex and address) will be securely sent to Services Australia.

When we request this information, there is a small risk to your privacy. However, when we receive these data from the health department, a unique identification number will replace your personal information. This should reduce the risk to your privacy. To ensure your confidentiality, we will also adhere to strict guidelines for data transfer, data storage and data access.

Information about inpatient hospital admissions, emergency department visits, survival, use of medications, outpatient services and cost of each visit at the hospital will be requested from state government data custodians. This is called Data Linkage. To get your health information using Data Linkage, the study team will collect personal information about you, including your hospital UR number, name, date of birth, gender and address. The study sponsor (The University of Queensland) will collect, store, and send the above personal details to the Data Linkage office in a safe manner. Using these details, the study team will link your study information with state government health information. Once it is linked, all personal information (including name, date of birth and address) will be removed. 

To maintain confidentiality of your information, we have processes in place. These include removing information that can tell who you are, using study numbers and following strict guidelines about data transfer, storage and access. If you decide to withdraw your consent for data linkage, the study team this information will not request this information from state government. The data obtained from state linkage will not be shared with external researchers for future unspecified study.

What will happen to my test samples (additional information)

Researchers are trying to learn more about ADPKD and how your body reacts to metformin. You are also being asked to provide consent for the collection of extra blood during some of your study visits. This blood will be frozen and stored in a confidential manner for testing later. Your samples will be labelled with a study code only, not your name, address or hospital number. These samples will be tested at a laboratory in Australia or at a research laboratory outside Australia explicitly approved by the trial global steering committee and which is included within the ethical approval of this trial within that country.

Although the chance is low, if blood and urine sample tests incidentally find any health-related issues, you and your treating doctor/s will be notified as soon as practicable for further assessment and to seek appropriate treatment.

Your samples may also be used for future collaborative research studies related to ADPKD not yet thought of. These future research studies will only use your samples with the approval from a Human Research Ethics Committee. We don’t know how long these samples will be stored and you won’t be informed of the results of these tests.

Will you be doing any genetic tests? [Delete if not applicable at the site name].

You are also be asked if the researchers can keep an extra blood sample to test for genetic (DNA) markers. Genetic research looks specifically at your DNA (which is passed down from your parents). This genetic testing will only be carried out for the purpose of ADPKD and chronic kidney disease-related research purposes. In this research, we will not be testing for or analysing other genes known as actionable incidental finding associated genes. There are approximately 59 such genes at present and they can be associated with some forms of inheritable cancers and nervous system conditions and are beyond the scope of this research. However, we may identify other genes that could indicate other health-related issues. If this occurs, you and your treating doctor/s will be notified as soon as practicable to find specific services to seek genetic guidance. You can decline to be informed of these findings in the consent form.

None of your genetic related information will be used for any purpose other than this study without seeking your further consent, unless required by law.

If you don’t want to consent to the collection of your samples for genetic testing, you can still participate in the study. You can decline genetic testing in the consent form.

What happens when the study ends?

After the study ends, your doctor will discuss the options you have with regards to the continuing treatment of your kidney disease. Once the study is complete and the results are known, a written plain English summary of the results of the study will be made available to your study staff. You can request a copy of this summary from the study staff.

What if I withdraw from this study?

You are under no obligation to continue with the research study. You may change your mind at any time about participating in the research. People withdraw from studies for various reasons and you do not need to provide a reason.

You can withdraw from the study at any time by completing and signing the ‘Participant Withdrawal of Consent Form’. This form is provided separately and is to be completed by you and supplied to the research team if you choose to withdraw at a later date.

If you decide to withdraw from this research, please notify a member of the research team before you withdraw. This notice will allow that person or the research supervisor to discuss any health risks or special requirements linked to withdrawing.

If you do withdraw your consent during the study, the trial doctor and relevant research staff will not collect additional personal information from you, although personal information already collected will be retained to ensure that the results of the study can be measured properly and to comply with law. You should be aware that data collected by the research team up to the time you withdraw will form part of the research results.  If you do not want them to do this, you must tell them before you join the study.

If you decide to withdraw from study treatment, you will be asked to attend follow-up visits to allow collection of information regarding your health status. Alternatively, the investigator/sponsor will request permission to access your medical records for collection of follow-up information for research and analysis.

Will I have to pay anything?

No. The trial treatment and medical tests are provided by the sponsor. Your treatment will be free of charge to you in the same way it would be if you were not in this trial.

How does this research differ from standard care?

You will receive standard care regardless of whether you take part in the trial or not. If you decide to take part you will be asked to do some things in addition to standard care. These include taking the study medication, completing surveys and blood and urine tests. There will be some extra trial appointments as described in sections 3 and 4. 

Destruction of data

TBC

If at any time anything is unclear or you have any questions, please make sure to ask your doctor who would be happy to help and answer your questions.