(Testing a new food supplement for women with mildly abnormal cervical smears.)

PATIENT INFORMATION SHEET

You are being invited to take part in a research study. Before you decide whether to participate, 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 friends and relatives 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.

What is the study about?
Women who have had their first mildly abnormal or second borderline abnormality are usually invited to have a repeat smear in six months time. We would like to find out if giving a supplement for six months reduces the number of women who have an abnormality at their repeat smear in six months time.

What is the supplement?
The supplement is called diindolylmethane or DIM for short. DIM is found naturally in certain vegetables such as cabbages and broccoli. It is further formed during chewing and digestion of these vegetables from a related plant substance. To receive the amount of DIM that is in the supplement you would need to eat at least two raw heads of cabbage per day.

Will I actually receive the supplement?
We want to compare what happens when you take the supplement with what happens without it. Two out of three women will receive the supplement, one out of three will receive a placebo (a dummy capsule). You will be randomly chosen to receive either the supplement or the placebo. Neither you nor the researchers will know which capsule you are given.

During the study you will take two capsules daily with a meal.

Why have I been chosen?
All women who have had one mildly abnormal or two borderline abnormal smears in your area have been invited to participate in the study. We hope to recruit at least 600 women. It is up to you to decide whether or not to take part. If you do decide to take part you will be asked to sign a consent form. Please keep this information sheet. If you decide to take part you are still free to withdraw at any time without giving a reason. This will not affect the standard of care you receive.

What would I have to do?
If you agree to take part in the study, we would take an extra smear from your cervix at the beginning of the study and, if you agree, may also take a photograph of your cervix at the same time. The photo will be taken with the help of a colposcope, which is a form of magnifying glass. The colposcope helps us to examine your cervix in detail. The photo will only show your cervix, no other areas of your body will be seen. The extra smear sample will be stored so that it can be tested in the future in the same way as your smear test and also for human papillomavirus (HPV) or for other markers that may be useful in cervical screening. We would also like to collect a sample of your urine. This might be tested at the end of the study.

You will then be given a box of capsules, which will either contain the supplement or the placebo. You will be asked to take two capsules once a day with a meal.

You will be asked to come back after three months and you will be asked to bring all your remaining capsules with you. We will ask you questions to make sure you have no problems with the capsules and we will collect some urine. No smear test will be taken at this visit.

After six months of taking the capsules, you will be asked to return for your final visit. Again we will ask you to bring any remaining capsules. A smear will be taken from your cervix, which can be tested in the conventional way and for HPV infection. A repeat photograph of your cervix will be taken, if this was done at the start. A detailed examination of your cervix will be carried out (called colposcopy). If there are any visible abnormalities on your cervix, a biopsy may be taken. Again, we will collect a urine sample. We will also ask you to complete a short questionnaire with one of the study team at the beginning and end of the study. The questionnaire asks about contraception, smoking, diet, pre-menstrual syndrome (PMS) and any other medications prescribed by your GP. We will also ask if you have had any side effects related to the food supplements.

After this visit, you will be treated and followed up in the same way as if you had not been taking part in the study.

What is HPV infection?
The human papilloma viruses (HPV) are a group of more than100 different types of viruses. Some types can cause genital warts and others can very occasionally cause cervical cancer. Both of these types are extremely common and most disappear without treatment. We would like to find out if the supplement helps to reduce HPV infection rates.

How will I receive my results?
Your smear test, colposcopy and any biopsy results will be sent to you in the usual way. You will not be informed of any other tests that we may carry out on your smear as these will be purely for research purposes.

Will I see the results of the study?
We will be happy to tell you about the overall results of the study. Please inform the researcher if you would like us to do this.

What happens to information about me?
All information that is collected about you during the course of the research and the results of the tests that we carry out on your cervical sample will be kept strictly confidential. We will make sure that your name and address are kept separately from any other information about you, so that this information only be linked back to you by those directly involved in your clinical care.

Will my GP be told that I am taking part?
We would like to inform your GP that you are taking part in this study. We will ask you to consent to this when you sign the form saying that you are prepared to take part in the study.

What are the possible advantages of taking part?
Taking the supplement may reduce the likelihood that you need further treatment for an abnormal smear test.

The examination at the end of the trial will be more detailed than a normal smear test.

You will have contributed to a study that may lead to a reduction in the number of women requiring treatment following cervical screening.

You will have helped evaluate a natural substance that may have value as a potential preventive for cervical cancer.

The supplement (BioResponse-DIM®) may also reduce symptoms of premenstrual syndrome (PMS) and facilitate weight loss if you are dieting.

What are the possible disadvantages of taking part?
The unwanted effects of taking DIM are mild, reversible and uncommon. They might include nausea, dyspepsia (mild stomach upset), and flatulence (intestinal gas), belching and bloating. Migraine headaches may be worsened during treatment. You may note a harmless darkening of the colour of your urine, if you are not drinking very much liquid.

You will be asked to undergo one extra examination at the start of the trial.

When should I not take part in the study?
The research team will check any exclusion criteria before you sign the consent form.
The following is a list of the exclusion criteria:
Women known to be pregnant or are trying to become pregnant in the next 8 months and those who are breast feeding should not enrol into the study.
Women on any form of immunosuppressive drugs.
Women on any proton pump inhibitors (for ulcers or reflux).
Women taking warfarin, theophyllin or omeprazole.
Women under surveillance for previous abnormal cells on the cervix.

What if I have an adverse reaction?
If you think you are having an adverse reaction to DIM, contact the research team Dr. Gudrun Rieck or our research nurse (Tel No 029 2074 5365) or your own doctor.

Who is organising the research?
The research is being jointly run by Cancer Research UK, University of Wales College of Medicine and Cervical Screening Wales.

How can I obtain more information?
Please ask us if there is anything, which is unclear or if you would like more information regarding the study.

Dr. Gudrun Rieck, Clinical Research Fellow, Department of Obstetrics and Gynaecology, University of Wales. Tel No: 029 2074 5365
Mrs Ceri McGuire, Mrs Susan Ashman Research Nurse. Tel No: 029 2074 5365

Prof Alison Fiander, Department of Obstetrics and Gynaecology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN. Tel No: 029 20743235