PATIENT INFORMATION SHEET:

MINIATURO™-I SYSTEM STUDY IN TREATMENT OF

INTERSTITIAL CYSTITIS

1.    Study Title:

Safety and preliminary efficacy study for the miniaturo™-I system for the treatment of patients diagnosed with Interstitial Cystitis

2.    Invitation paragraph

You are being invited to take part in a research study.  Before you decide, it is important for you to understand why the research is being done and what it will involve.  Please take time to read the following information carefully and discuss it with others if you wish.  Ask us if there is anything that is not clear or if you would like more information.  Take time to decide whether or not you wish to take part.

Thank you for reading this.

3.    What is the purpose of the study?

The purpose of this study is to determine whether miniaturo™-I, a new medical device, is safe and effective to use for the treatment of female IC. The study will last for a period of about 1 year. However, once the study is over, you will continue to be looked after by your doctor every six months for a period of up to 5 years after the surgery.

The safety of the system will be determined by counting the number of problems that occur during the study, such as pain or discomfort, or more serious problems that might need admission to hospital.

4.    Why have I been chosen?

You were chosen to participate in the study, because your physician thinks that your physical and medical condition are compatible with the requirements set by the study sponsor.
A total of 30 patients will be recruited to this study worldwide and 10 of them will be recruited in the Australia .

5.    Do I have to take part?

It is up to you to decide whether or not to take part.  If you do decide to take part, you will be given this information sheet to keep and be asked to sign a consent form. If you decide to take part you are still free to withdraw at any time and without giving a reason.  A decision to withdraw at any time, or a decision not to take part, will not affect the standard of care you receive

6.    What will happen to me if I take part?

6.1     General
If you decide to take part in the study you will be recruited to the study for 12 months (1 year). The research itself will last for several more years until all patients are recruited and have completed the study.

The miniaturo ™-I therapy involves two stages:

a. miniaturo-I test system (MTS-I)

b. Surgical implantation of the system.

Patients who get relief from their IC symptoms with the test system would then be offered the long-term implant.

6.2     Recruitment visit

Before you try the test system your doctor will go through your medical history with you. You will need to repeat urodynamic and cystoscopy tests if you have not preformed them in the last six months. Your doctor will also collect a blood sample and urine. These are routine examinations done to patients diagnosed with IC.

Additionally, your doctor needs to know:

·         How long you’ve had IC

·         If you have any other urinary symptoms

·         What past procedures or prescription drugs you have tried

·         If you have any other diseases or illnesses

·         What medications you are currently using

You will be asked to fill-in questionnaires and an Interstitial Cystitis diary before your visit to the hospital for a period of 3 days. In the IC diary you will be asked to write down your symptoms (voiding habits and pain events) for 3 consecutive days. This will give your doctor a “baseline” record of your symptoms prior to the therapy. This information will help you and the doctor to decide whether you are suitable to the miniaturo™-I test system.

6.3     miniaturo™-I Test System visit

miniaturo™-I Test System (MTS-I) is the first step of miniaturo ™-I therapy and will last for approximately 6 hours in the outpatient clinic. The MTS-I consists of electrical stimulating device, about the size of a cigarette lighter that is worn on a pouch belt around your waist. The electrostimulator delivers mild intermittent electrical pulses to the pelvic muscles. The lead would be placed in a very small cut near the vagina, performed under local anaesthetic to avoid pain.

After being connected to the test system your doctor will set the best stimulation level, using a communication system, according to your sensations (comfortable, but aware of the stimulation).  Once individual settings have been programmed, you will receive an explanation about how to use the temporary device.

You will be asked to wear the system for 6 hours and record in the IC diary how the therapy affects your symptoms. Your symptoms may improve or even completely disappear. Even so, whenever an event of discomfort is felt, you are asked to turn the system OFF using the safety magnet that will be given to you, and immediately contact your doctor.

The test procedure has several advantages.

·         It’s a temporary procedure in which you can learn whether the miniaturo™-I therapy can help you without committing to a long-term treatment.

·         It allows you to “test drive” the miniaturo™-I therapy.

·         It allows you to feel what stimulation is like. 

At the end of the test, the system is removed. Based on the results of your test trial, your doctor may recommend an implantable miniaturo™-I system to improve your bladder and pain symptoms.

6.4    miniaturo™-I implantation

The implantation of the miniaturo™-I system is the beginning of the second stage of the study. The electrostimulator and stimulation lead are both implanted under the skin under local or general anaesthetic (depending on your wishes). Doctors usually implant the miniaturo ™-I system in two steps: First, the stimulation lead and then the electrostimulator. This entire procedure typically takes 25 to 40 minutes and is performed in the operating theatre. You will be prescribed antibiotic medication in order to reduce the risk of infection after the surgery and can go home the same day if you are feeling OK.

In order to implant the system, the doctor will make two small cuts:

One short 4 cm cut in your lower abdomen just above the pubic bone, where the electrostimulator is positioned; the second, where the stimulation lead tip is inserted (a small incision near the vagina to implant the lead).

6.5     System activation visit

Two weeks after the procedure, you will return to your clinic, where the doctor will remove your sutures and will set the stimulation levels for you, using a communication system connected to a laptop computer. The stimulation level will be set according to your sensations (comfortable, but aware of the stimulation).

This visit will take approximately 1 (one) hour and will be preformed in your outpatient clinic.

You will receive a safety magnet that allows you to control the internal device by switching it ON or OFF (identical to the one used during MTS-I procedure) if you feel it is necessary.

6.6     Follow up visits

You will be asked to attend follow-up visits 1, 3, 6 and 12 months after the activation of the implanted system. Each visit will last approximately 20 minutes at you doctor’s clinic. Between the visits we will ask you to complete the IC diary for 3 consecutive days to record how the treatment affects your voiding and pain symptoms.

The change in symptoms will be estimated according to your personal impressions. Your symptoms may improve or even completely disappear. During these visits, you will be asked to fill in a quality of life questionnaire. Additionally, you may discuss your urinary and pain symptoms with your doctor and decide whether the stimulation levels need adjustment. If so, your doctor will be able to make the necessary changes.

Once the study is over you will continue to be followed up by your doctor every six months for a period of 5 years.

Other than the above visits, you will not need to visit the GP (or clinic) more often then your usual treatment. We will pay all study-related travel expenses.

7.    What do I have to do?

7.1     Lifestyle limitation

As with any surgery you should let your body heal. Right after the surgery you should “take it easy “ and avoid lifting heavy things, stretching and avoid causing strain on the abdominal stitches. You will be asked to avoid sexual intercourse and bathes (showers are allowed) for the first 2 weeks.

7.2     Medical procedures

You should always tell other doctors and nurses that you have an implanted electrostimulator device. The right safety measures will allow most medical procedures to be performed. Some investigations, such as Magnetic Resonance Imaging (MRI – a type of scan), and some treatments, are not possible. We will advise you at the first visit regarding any existing medical conditions.

7.3     Home or occupational environment

You will be given a safety magnet in order to switch the device off immediately if you feel it is necessary. The safety magnet may damage televisions, computer disks, credit cards, and other items affected by strong magnetic fields. You should always store your magnet with its protective plate.

It is recommended that while using the implanted system you should not operate potentially dangerous equipment such as power tools.

Home appliances that are properly grounded should not interfere with the miniaturo™-I system operation, and may be used.

7.4     Theft detectors and screening devices

Theft detectors found in department stores and airport/security-screening devices may cause the electrostimulator output to switch ON or OFF. It is also possible that you will experience a momentary increase in your perceived stimulation as you pass through these screening devices. Higher levels can be unpleasant or “shocking”. If you experience a change in stimulation levels you should exit from the screening device. Those devices do not damage the system, and it will continue to work normally afterwards.

Your doctor will provide you with a card showing that you are implanted with an electrostimulator to show to airport and store security if necessary. 

Other then the above mentioned the miniaturo™-I will not cause any lifestyle limitation and you could continue your regular day routine.

8.    What is the treatment that is being tested?

BioControl miniaturo™-I system is an experimental, electrical stimulator system. The miniaturo™-I system consists of an electrostimulator and a stimulation lead which are both implanted under the skin. The stimulator delivers mild electrical pulses via the stimulation lead to the pelvic floor muscles.

The miniaturo™-I is about the size of a cigarette lighter and its dimensions are 47X53X10 mm. The stimulation lead (a thin wire) is 35 cm long and its diameter is 1.4mm.

You will determine the best stimulation levels according to your sensations. The electric pulse induces relaxing effects on the bladder wall with the intent to obtain control of your bladder.

A non-invasive communication system, which consists of a communication system connected to a laptop computer, allows your physician to control the implanted system.

System components are illustrated in figure 1.

Figure 1: miniaturo™-I system

You will receive a patient identification card with details about your implanted system and emergency contact persons in Australia . You should carry your system ID card with you all the time.

9.    What are the alternative therapies?

Scientists have not yet found a cure for IC. Because the causes of IC are not yet known, treatment is aimed to relieving symptoms. Most of the treatments are not efficient and symptoms often return after a short period. However, IC symptoms may be improved to some degree by one or more of the following treatments:

·         Bladder distension (stretching the bladder under anaesthetic)

·         Bladder instillations (placing drugs in the bladder with a catheter)

·         Drugs taken by mouth.

·         Transcutaneous electrical nerve stimulation.

·         Sacral nerve stimulation implant (another type of implant located in the back)

·         Diet alteration and quitting smoking

·         Exercise

·         Surgery (cystectomy - removal of the urinary bladder or bladder augmentation - a graft of material used to increase the size, shape, or volume of the bladder)

10.    What are the side effects of any treatment received when taking part?

The potential side effects related to this study are the side effects of surgery (infection, skin irritation, blood clotting, etc.), anesthesia (allergy or sensitivity to anesthetic drug, breathing arrest, etc.), and electrical stimulation (transient electric shock, painful or irregular stimulations, tissue damage, etc.).

In any case, whenever you feel unusual or unexpected event or you experience less control of your symptoms or you becoming concerned, you should contact your doctor (detailed below and in your system ID card).

11.    What are the possible disadvantages and risks of taking part?

The possible risks include, but are not limited to, bleeding during the insertion operation; pain where the electrostimulator unit is implanted in the abdomen; movement of the lead leading to technical problems; pain where the lead is sited; infection; sensation of momentary electrical “shock”; skin irritation; expulsion of the device from your body; failure of the system to function properly; unsatisfactory changes in bladder and bowel functions; allergic reaction; and other technical problems.

As safety in pregnant women has not been evaluated for this system, it is possible that if the treatment is given to a pregnant woman it will harm the unborn child. Pregnant women must not therefore take part in this study; neither should women who plan to become pregnant during the study. If you are at risk of pregnancy you may be asked to have a pregnancy test before taking part to exclude the possibility of pregnancy. If you are not planning to have a child, you must use effective contraceptive during the course of the study. If you find yourself pregnant while taking part in the study you should immediately tell the research doctor.  

If you own a private medical insurance plan you should consult with the insurance company before agreeing to take part in the trial.  You will need to do this to ensure that your participation will not affect your medical insurance.

Sometimes, during a clinical trial, patients might be diagnosed with a medical condition that they are not aware of. If the medical condition had occurred due to the miniaturo™-I treatment you would be compensated according to the “Association of British Health Industries” (ABHI) and the “Australian Pharmaceutical Manufacturers Association” (APMA) guidelines (you can find more details about compensation on page 8 section 15 in this sheet).

If it were determined that the new medical condition is not related to the miniaturo™-I therapy you will be treated for this new condition by your doctor. If the new medical treatment will affect the miniaturo™-I treatment your doctor might recommend that you withdraw from the study and the miniaturo™-I will be removed from your body.

Any new information regarding your medical condition will be recorded in the study files; however, your identity will remain confidential.

12.    What are the possible benefits of taking part?

The study sponsor and the investigators feel that there is potential benefit to your IC symptoms as a result of the miniaturo™-I treatment.

The miniaturo ™-I treatment can potentially reduce the need for analgesics (pain killers), improve urinary symptoms and increase your overall health and quality of life. Moreover, the miniaturo ™-I treatment is completely reversible and can be turned off at any time. The miniaturo ™-I system can be completely removed from your body at any time, at your request.

Results from past studies show that the miniaturo™-I treatment is an effective treatment for most study compatible IC patients.

So far, ten Interstitial Cystitis (IC) patients, average age of 54 years old (range 39-72 y), who had suffered IC symptoms for years and had failed previous simple treatments, were recruited to BioControl miniaturo™-I study.

The patients responded favourably to the miniaturo™-I treatment and demonstrated sustained improvement in urinary frequency, pelvic pain and their quality of life at the last follow up visit. At the mean follow up period, the number of times patients went to the toilet to urinate was by half, from an average of 32.4 times per day down to 15.7 times per day. The pain (on a scale of 1 to 10) was also reduced in all patients from a level of 4.9 to a level of 1.0 following miniaturo™-I treatment.

Positive impact of the miniaturo™-I therapy was demonstrated in various aspects of quality of life based on patient’s questionnaires.

As mentioned in the side effect section, several patients had two types of surgery related complications:

The first type is wound infection that was observed in four (4) patients who were treated and cured with short antibiotic treatment.  In the second complication type, one (1) patient had required stimulation lead replacement due to improper lead implantation. After replacement of the stimulation lead, the patient had fully recovered.

We hope that the treatment will help you, although this cannot be guaranteed. The information we get from this study may help us to treat better future IC patients.

13.    Contact for further information

If you would like further information, please feel free to contact: