Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00464022 |
| Other study ID # |
2006-3277 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
April 18, 2007 |
| Last updated |
October 16, 2007 |
| Start date |
November 2006 |
| Est. completion date |
July 2007 |
Study information
| Verified date |
October 2007 |
| Source |
Rikshospitalet University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Norway:National Committee for Medical and Health Research Ethics |
| Study type |
Interventional
|
Clinical Trial Summary
Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire
small bowel. In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel
to secure good visualisation. All endoscopes used for GI endoscopy provide a gas
insufflation unit. Currently, air is used for this purpose in more than 90% of centres
throughout the world. The use of air, however, is far from ideal to use for insufflation in
GI endoscopy. After GI endoscopy, significant amounts of air are usually retained in the
bowel segment inspected (5). This air has to pass the GI tract and exit physiologically
through the rectum. Thus, abdominal pain and discomfort during and after the examination due
to the retention of air has been shown to be very common during and after endoscopic
procedures (5-9).
Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes,
several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to
result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in
several randomised trials (6-9). In these studies, CO2 insufflation almost completely
reduced procedure-related pain and discomfort.
To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is
a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are
insufflated during the procedure, leading to significant distension of the small bowel
during and after the examination.
One of the main technical difficulties in DBE is the formation of small bowel loops and
scarp angels during deep intubation of the endoscope. These loops and angels are the major
restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced
in air-distended bowel segments.
The aim of the present study is to examine whether CO2 insufflation leads to a reduction of
abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation
facilities a deeper intubation of the endoscope and thus a more complete examination of the
small bowel mucosa.
The study is designed as a two-centre randomised controlled trial. Randomisation to the two
treatment groups (CO2 or air insufflation) is performed on basis of the individual
participant.
Description:
Background The small bowel has been a large blind spot for gastrointestinal (GI) endoscopy
as, until recently, the small bowel was not accessible with conventional endosocopes.
Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire
small bowel. The method was first described by Yamamoto et al. and May et al in 2001 and
2003, respectively (1,2). Since then, DBE has spread to a rising number of centres around
the world. Both endoscopic diagnosis (e.g. by biopsy) and treatment can be easily performed
using DBE. The first larger series, recently published, demonstrate that DBE is feasible in
scoping large parts of the small bowel, with total small intubation possible in about 30-40%
of cases (3,4).
In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel to secure
good visualisation. All endoscopes used for GI endoscopy provide a gas insufflation unit.
The gas is pumped on demand into the area examined by the endoscopist via a gas tube
incorporated in the endoscope. Currently, air is used for this purpose in more than 90% of
centres throughout the world. The use of air, however, is far from ideal to use for
insufflation in GI endoscopy. After GI endoscopy, significant amounts of air are usually
retained in the bowel segment inspected (5). This air has to pass the GI tract and exit
physiologically through the rectum. Thus, abdominal pain and discomfort during and after the
examination due to the retention of air has been shown to be very common during and after
endoscopic procedures (5-9).
Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes,
several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to
result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in
several randomised trials (6-9). In these studies, CO2 insufflation almost completely
reduced procedure-related pain and discomfort.
To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is
a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are
insufflated during the procedure, leading to significant distension of the small bowel
during and after the examination.
One of the main technical difficulties in DBE is the formation of small bowel loops and
scarp angels during deep intubation of the endoscope. These loops and angels are the major
restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced
in air-distended bowel segments.
The aim of the present study is to examine whether CO2 insufflation leads to a reduction of
abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation
facilities a deeper intubation of the endoscope and thus a more complete examination of the
small bowel mucosa.
Hypothesis
1. The use of CO2 in DBE leads to a reduction in abdominal pain for the patient when
compared with the use of air.
2. The use of CO2 in DBE leads to deeper intubation when compared to air insufflation.
Methods Study design The study is designed as a two-centre randomised controlled trial. The
participating centres are Rikshospitalet University Hospital, Oslo, Norway and University
Hospital Muenster, Germany.
Randomisation to the two treatment groups (CO2 or air insufflation) is performed on basis of
the individual participant. Equally large groups are randomised, using block randomisation
(blocks of six patients) for each of the participating centres. Randomisation (using SPSS
statistical software package) is performed by an independent researcher, who is not part of
the DBE team.
Individuals eligible for inclusion are patients referred for DBE at the trial centres who do
not fulfil one of the following exclusion criteria:
- Age under 16 years
- Inability to understand information for participation
- Refusal of participation
All eligible individuals are informed about the nature of the study. All individuals provide
written informed consent before entering the trial. Patients who do not wish to participate
in the present trial are treated according to standard procedures (using air insufflation).
All procedures are performed by experienced endoscopists. Both patients and endoscopists are
blinded with regard to type of gas used for any particular patient.
Sedation is performed according to current standards at the centres.
Double-balloon procedure DBE is performed using the DBE endoscope system (Fujinon Inc,
Japan), as described in the literature (1-4). The DBE endoscope consist of a 200-cm long
video endoscope with an outer diameter of 8.5 mm and a flexible overtube with a length of
145 cm and an outer diameter of 12 mm. Latex balloons are attached to both the endoscope and
the overtube. These balloons are inflated and deflated during insertion, as described
elsewhere in detail (1,2).
Gas insufflation CO2 is insufflated using Fujinons equipment (or other, to be specified) Air
is insufflated using the ordinary air inlet system of the endoscope rack. The air inlet
button is hidden from the view of the endoscopist to prevent unblinding (technical details
to be specified in cooperation with company).
Evaluation of pain and discomfort A questionnaire is used to classify patient pain during
and after the procedure. Visual analogue scales (100-mm) are used to quantify abdominal pain
during the examination and at 1, 3, 6, and 24 hours after the procedure, as validated in
recent studies (7,8). The questionnaire is given to every participant after the procedure,
to be filled in the next day, and mailed back to the respective trial centre using prepaid
envelopes.
Evaluation of ERCP examination parameters All procedure parameters of interest (e.g.
duration, depth of insertion, use of sedatives) are registered by the endoscopist
immediately after the examination using the existing GI lab databases.
Ethics The regional ethics committees of the participating centres will be asked for
approval of the study protocol.
Power analysis A 15% reduction in mean pain score on VAS is considered to be clinically
important to detect. There are no studies available regarding this outcome in DBE.
Therefore, pilot study will be performed with 20 included patients in every group (air/CO2).
The results of the pilot study will estimate the standard deviation needed to calculate
power and thus size of the study.
Ownership Data are owned by the respective centres. Publication of the study results is
planned in a peer-reviewed journal. Michael Bretthauer and Dirk Domagk will co-ordinate
study design, data generation and analysis and a first manuscript draft. Michael Bretthauer
and Dirk Domagk will be the first authors of the planned publication, the other members of
the study groups will be co-authors.
Budget All procedures in the present study are performed in ordinary patients, with ordinary
staff and endoscopists. Therefore, no extra costs occur for personal. For the purpose of the
present study, however, some technical equipment has to be purchased (to be specified).
Financial funding is needed for meetings of the study group and prepaid envelopes.
References
1. Yamamoto, Sekine Y, Saito Y, et al. Total enteroscopy with a non-surgical steerable
double-balloon method. Gatrointest Endosc 2001;53:216-20
2. May A, Nachbar L, Wardak A, et al. Double-balloon enteroscopy: preliminary experience
in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy
2003;35:985-91
3. May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull enteroscopy) of the
small bowel: feasibility and diagnostic and therapeutic yield in patients with
suspected small bowel disease. Gastrointest Endoc 2005;62:62-70
4. Ell C, May A, Nachbar L, et al. Push-and pull enteroscopy in the small bowel using the
double-balloon technique: results of a prospective European multicenter study.
Endoscopy 2005;37:613-6
5. Hussein AMJ. Carbon dioxide insufflation for more comfortable colonoscopy. Gastrointest
Endosc 1984; 30:68-70
6. Stevensen GW et al. Pain following colonoscopy: elimination with carbon dioxide.
Gastrointet Endosc 1992;38:564-567
7. Bretthauer M, Thiis-Evensen E, Hoff G, et al. A randomized controlled trial to assess
the safety and efficacy of carbon dioxide insufflation in colonoscopy. Gut 2002;
50:604-607
8. Bretthauer M, Hoff G, Thiis-Evensen E, et al. Carbon dioxide insufflation reduces
discomfort due to flexible sigmoidoscopy in colorectal cancer screening. Scand J
Gastroenterol 2002, 37:1103-8
9. Sumanac K, Zealley I, Fox B , et al. Minimizing postcolonoscopy abdominal pain by using
CO2 insufflation: a prospective, randomized, double blind, controlled trial evaluating
a new commercially available CO2 delivery system. Gastrointest Endosc 2002;56:190-4
Information and consent Research study: Insuflation of carbon dioxide(CO2) in double balloon
enteroscopy
Dear patient
You are hereby kindly invited to participate in a research study while undergoing your
planned endoscopic investigation of the small bowel (DBE, double balloon enteroscopy)
During this examination, it is common practice to insufflate gas into the small bowel to
provide the examiner with an adequate view. At the vast majority of hospitals around the
world, ordinary room air is used for insufflation. However, the insufflated air can produce
pain and abdominal discomfort for patients during and in the hours after the examination.
There is some evidence that the use of carbon dioxide gas (CO2) instead of air can reduce
abdominal pain after examination. In this study, we would like to find out if this is true.
Study participants will be divided by random into a group that receives CO2 during the DBE
examination and one group that receives air.
Both the endoscopist and you as a patient do not know which gas is being used. Only the
endoscopy assistant knows the type of gas used during your examination. After the
examination, you will receive a short questionnaire about any complaints or discomfort,
which we would like to ask you to fill in at home and mail back to the hospital.
If you decide not to participate in the study, your examination will be performed with the
use of air insufflation (standard method).
The present study has been approved by the ethics committee. All information will be treated
strictly confidential and only for research purposes within this study. Participation is
free of charge and not mandatory. You may decline your participation at any time.
Yours sincerely
Dr. med. Michael Bretthauer (tlf:)
Written informed consent I hereby declare my participation in the abovementioned research
study. I am aware of that participation is voluntary.
Date Signature
Vedlegg C
Carbon dioxide versus air insufflation in double-balloon endoscopy
"Patient questionnaire (Version 300606), Michael Bretthauer
This questionnaire is to be filled in the day after the procedure and to be mailed back to
the GI lab.
Patient ID
1. Was the examination any painful??
Please score the degree of pain with a vertical dash on the scale below, between No
pain (left margin) and very heavy pain (right margin).
No pain Very heavy pain
2. Did you have any abdominal pain or distension after the examination?
Please score the degree of pain with a vertical dash on the scale below, between No pain
(left margin) and very heavy pain (right margin).
No pain Very heavy pain
1 hour after the exam
3 hours after the exam
6 hours after the exam
24 hours after the exam
Please use the back of the questionnaire for any comments
