5-HT IBS-C & IC study Version 3  31/03/08
 
SUBJECT INFORMATION
Version 3 31st March 2008

5-Hydroxytryptamine (a body chemical) signaling in patients with idiopathic constipation (IC) and irritable bowel syndrome with constipation (IBS-C): Is there a common abnormality which is related to delayed gastrointestinal transit (passage of food through the gut) or rectal insensitivity?


You have been 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 friends, relatives and your GP if you wish (your GP will be informed if you choose to participate in this study).  Ask us if there is anything that is not clear or if you would like more information.

Before taking part in the study you will be asked to sign and date the consent form.  Your participation is voluntary and you are free to refuse to participate or withdraw from the study at any time.  Your decision will not affect your relationship with your doctor or your future healthcare.

This research project has been reviewed by the South Manchester Research Ethics Committee and it has been agreed that it may go ahead.

There are no personal medical benefits resulting from your participation in your study.

If you have taken part in a drug study within the 30 days prior to entry into this study, you should inform the study investigator or member of their team, as this will exclude you from taking part in this study.

You will be given a copy of both the information and consent forms.  Please keep them safely.

Why are we doing this study?
Irritable bowel syndrome with constipation (IBS-C) and idiopathic constipation (IC) are common disorders, although their causes are not well understood.  A chemical called 5-hydroxytryptamine (5-HT) which can be measured in the blood is thought to be involved in these conditions but it is unclear whether there is a similar abnormality in these two conditions and how the levels of blood 5-HT relate to gastrointestinal transit (ie the speed at which food moves through the gut) and the sensitivity of the gut, which can either often be under (in-) sensitive in these two conditions.   The aim of this study is to investigate whether patients with IBS-C and IC have similar abnormalities in blood levels of 5-HT compared with healthy volunteers and to see whether this relates in any way to the speed of gastrointestinal transit and the sensitivity of your rectum

How many people will take part?
A total of 72 people will take part, 24 patients with irritable bowel syndrome with constipation, 24 patients with idiopathic constipation and 24 healthy volunteers.  All visits and assessments will be carried out in the Neurogastroenterology Unit, Wythenshawe Hospital, Manchester under the supervision of Dr L A Houghton and Professor P J Whorwell.

What does the study involve?
This study will consist of 4 phases:

  1. During the first visit, a doctor will ask you about your medical history, and he/she will record your recent drug history.  In addition, you will have a complete physical examination (including physical rectal examination), and tests will be performed on samples of your blood and urine.  This will include drugs of abuse and pregnancy screening tests, either of which if positive will exclude you from the study. In addition a 12 lead ECG of your heart function will be carried out, and you will be asked to complete a simple one page questionnaire which accesses anxiety and depression levels (the Hospital Anxiety and Depression questionnaire).  If you are a patient with either IBS-C or IC (ie not healthy volunteers) aged over 50 years and if you have not had a colonoscopy or a flexible sigmoidoscopy (a visual examination of your bowel) or air contrast barium enema (an X-ray examination of your bowel) during the 5 years before you start the study, you will also have one of these tests performed.  If you are 50 or younger these tests will only be performed if your doctor believes it to be appropriate.

  2. You will have to return for the next visit after 7-9 days during which time you will be asked to complete a diary just before going to bed in which you score the severity of your tummy pain, bloating and bowel urgency you have experienced during the day. In addition if you open your bowels, we would like you to record the time and consistency of these bowel movements.  If eligible to continue in the study, you will attend the unit for one full day (day 0: at 9am).  A small plastic tube (cannula) will be inserted into a vein in your arm so that blood samples can be taken over 6 hours (13 samples of 6ml each equating to total blood volume taken of 78ml) to assess the levels of 5-HT in your blood.  After the first 5 samples (2, 1.5, 1.0 and 0.5 hour prior to meal, and immediately before meal, time=0), you will be given a meal which will be a carbohydrate rich meal of spaghetti on toast, a cake and glass of water.  Throughout the study you will be asked hourly if you have any gut symptoms.  At the end of the study, the cannula will be removed and you will be given three different sets of radio-opaque markers (24 markers in each) to take home with you. You will be asked to swallow the first set of markers at 8.30am on the next day with 100ml water (day 1), the second set of markers at 8.30am on the following day (day 2), and the third set of markers at 8.30am on the day after that (day 3).

  3. On day 4 you will be asked to attend the X-Ray Department at 8.30am and a single abdominal x-ray will be taken, and the markers used to estimate whole gut transit time.   (One abdominal x-ray gives an effective dose of radiation of 0.44 mSv (a round trip from New York to Tokyo would give a dose of 0.2mSv). The one abdominal x-ray you will receive is equivalent to about 5 months of average UK background radiation and is considered a very low risk by the Health Protection Agency). Some of you who have IBS with constipation or idiopathic constipation will require one of these x-rays to determine your large bowel transit anyway, as part of your hospital clinical assessment. In this case you will not be receiving any additional x-ray exposure than you would have required for your normal clinical management. You will then be asked to bring the x-ray back to the Neurogastroenterology Unit where you will have your small bowel transit time assessed (this will take the rest of the day to perform).  This involves you rinsing your mouth out with mouthwash and then eating a meal containing 150g mashed potato and 120g baked beans.  Immediately after consumption of the meal you will be asked to rinse your mouth out once again. Expiratory breath samples will be taken for 1 hour before this meal and then at 10 minute intervals thereafter. A rise in breath hydrogen determines the arrival of the meal in the large bowel and breath samples will be taken until breath hydrogen increases by 10 parts per million (PPM) sustained for 20 minutes.   You will be asked to complete a symptom diary until your next visit to the unit (same type of diary completed before start of study).

  4. Within 14 days of these tests you will be asked to re-attend the laboratory after an overnight fast to have your rectal sensitivity assessed (the test takes about 60 minutes).  This again is often a test we do as part of your normal/routine clinical management.  It involves a balloon catheter being placed in your rectum and then whilst it is inflated you reporting the sensations you experience. This will allow us to determine whether you have a normally or under (in-) sensitive rectum.

? In addition, we ask you to stop smoking for 48 hours prior to study visits on phase 2, 3, and 4 and stop consuming alcohol and caffeine containing drinks for 24 hours prior to study visits on phase 2, 3 and 4 .

? And do not eat any food from midnight the night before study visits on phase 2, 3, and and to only drink water.   Please stop drinking water 2 hours before arriving at the hospital on phases 2, 3, and 4Consumption of foods and liquids will then be restricted during the study days, other than when the study meals are to be consumed.

All blood samples will be stored in the department until it is analysed; the sample will be identified by a code (rather than your name) while it is stored and being used in this research.  This code will allow your sample to be used without anyone knowing that it is your sample just by looking at the label.

At the end of this study, with your consent (see item 6 in consent form) the samples will be stored and may be used in future research.  If you do not wish your blood sample to be used for future research please indicate this by not initialing box 6, and at the end of the study, your blood samples will be disposed of.

What are the risks?
There is always an unknown element of risk associated with any procedure.  However, the risks to patients and healthy volunteers from these procedures are considered to be minimal.  Some temporary discomfort may occur during placement of the small plastic tube in the vein. Because of the x-ray, you must not be, or intend to become pregnant while participating in this study.  Some temporary discomfort may occur during the inflation of the balloon catheter in the rectum to record rectal sensitivity, but this should be mild and temporary.

If you are harmed by taking part in this study, there are no special compensation arrangements.  If you are harmed due to someone’s negligence, then you may have grounds for legal action.  Regardless of this, if you have any cause to complain about any aspect of the way you have been approached or treated during the course of this study, the normal National Health Services complaints mechanisms are available to you.

Will I be paid for the inconvenience?
You will be paid (at the end) an appropriate payment for any travel expenses incurred and for the inconvenience if participating in this study, this will be a sum of £200.  However, if for any reason you are unable to complete the study, you will be paid on a pro rata basis.

Your voluntary participation
Your decision to participate in this study is entirely voluntary and you are free to withdraw from the study at any time.

What do I do if I want to withdraw
You are encouraged to contact the investigator or laboratory should you decide not to continue your participation in the study.  He/she will explain the best way for you to discontinue your participation in the research study.

If you withdraw from the study, collected information may still be used.  However, any stored blood samples that can still be identified as yours will be destroyed if you wish.

The investigator may wish to stop your participation in the study
Your participation may be stopped for any of the following reasons:

? Failure to follow the investigators’ instructions.
? A serious adverse event which may require treatment or observation.
? The investigator decides that it is in the best interest of your health and welfare to discontinue.
? Insufficient enrolment in the study.

Who do I contact?
If during the course of this study you have questions concerning the nature of the research or your rights as a subject or you believe that you have sustained a research related injury, you should contact either Dr L Houghton or Dr C Shekhar on telephone number 0161 291 4188 / 0161 291 4191. 

In an emergency out of hours, you may contact Dr L Houghton or Dr C Shekhar by telephoning the operator of Wythenshawe Hospital on 0161 998 7070.  You will be asked to give you name and telephone number to the operator.  The operator will then contact one of the doctors, and the doctor will immediately ring you back.

You are free to withdraw from this study at any time without giving a reason.

What will happen to the results of the research study?
The results of this research will be published in an appropriate scientific medical journal.  You will not personally be identified in this publication.  Following publication the results of this research will be available to you to look at, if you wish.

Who is organizing and funding the research?
Dr L Houghton is the Chief Investigator of this research, and along with her research team is responsible for its organization. 

What about confidentiality?
If you decide to take part in this study, all the information about your participation in this study will be kept confidential.  Your name will not appear in any publications or reports produced from this study.

The study doctor will contact your general practitioner to inform him/her that you are participating in your study. 

Thank you for reading this information. If you wish to volunteer for this study please telephone Chander Shekhar on: 0161 291 4190 / 4191. Monday - Friday - 9am to 5pm.

 

Women with constipation and irritable bowel syndrome are required for a study. Click here for more information