Double/Single Balloon Enteroscopy Stiffening Wire RCT

Study Overview
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Brief Summary
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This is a randomized clinical trial examining the use of a stiffening wire to increase depth of maximal insertion during double and single balloon enteroscopy.

Detailed Description
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BACKGROUND Small bowel endoscopy has undergone a paradigm shift in the past decade. Prior to this, the small bowel was considered a 'black hole' due to our inability to visualize it endoscopically and the limited sensitivity of radiologic studies. This all changed with the development of capsule endoscopy, which gave physicians the ability to visualize the full length of the small bowel. Although widely considered a great leap forward, video capsule endoscopy is limited by its inability to perform any form of endoscopic intervention. Thus, something was needed to biopsy and treat the abnormalities detected with capsule endoscopy. Double balloon enteroscopy (DBE) was invented in Japan in 2001. Using an overtube and two inflatable balloons, DBE enabled deep intubation of the small bowel through a series of push and pull maneuvers to accordion the small bowel over the overtube. This procedure proved highly successful in the diagnosis and treatment of small bowel diseases. Subsequently, single balloon enteroscopy (SBE) was developed consisting of a single overtube balloon. Collectively, these techniques are called balloon assisted enteroscopy. Balloon assisted enteroscopy can be performed using an antegrade (through the mouth) or retrograde (through the anus) approach. The two approaches are considered complimentary since the antegrade approach enables visualization of the proximal and mid small bowel while the distal portion is seen with the retrograde approach. Complete enteroscopy, or visualization of the entire small intestine, occurs when an antegrade enteroscopy is performed and the tattoo left at the depth of maximal insertion is reached during a subsequent retrograde procedure. Although considered to be the gold standard for enteroscopy, this is rarely achieved outside of expert centres in Japan. The reason for this is because of loop formation in the small intestine, commonly referred to as looping (Figure 1). Looping typically worsens as the depth of insertion increases and eventually prevents forward migration of the enteroscope. Looping is not unique to enteroscopy and is a common problem encountered during colonoscopy. During colonoscopy, loops can be removed, by pulling back and torqueing the colonoscope. However, the loop often reforms when the colonoscope is pushed forward again. To counter this problem, colonoscopes have been developed with adjustable stiffness that can be changed during the procedure (Olympus Inc., Tokyo, Japan). Using this feature, the loop can be removed and the colonoscope stiffened prior to pushing forward to prevent loop reformation. Although variable stiffness is available in colonoscopes, the same technology cannot be incorporated into enteroscopes due to its much thinner diameter. Recently, an enteroscopy stiffening wire has been developed by Zutron Medical LLC (Kansas, USA). This through the scope wire can be inserted as needed to increase the stiffness of the enteroscope. In theory, this should improve the performance of DBE/SBE and translate into deeper insertion although this has never been investigated. The objective of this randomized clinical trial is to answer this question. STUDY DESIGN This is a single centre randomized clinical trial assessing whether a stiffening wire increases the depth of maximal insertion during DBE/SBE. Due to the nature of the procedure, blinding of the endoscopist is impossible. This is because even if a placebo wire is used, the enteroscope feels sufficiently different to enable unmasking. To mitigate the risk of bias, the enteroscopy will be recorded and outcomes assessed in a blinded fashion using the recorded video. Randomization will be in blocks of varying sizes and performed using sequentially labelled sealed envelopes. STUDY INTERVENTION After fasting overnight, sedation is given at the start of the procedure. This consists of either Propofol administered by an anesthetist or midazolam and fentanyl administered by the endoscopist. The enteroscope is inserted into the mouth, down the esophagus, though the stomach, and into the duodenum. Once in the small bowel, a series of push and pull maneuvers are used as previously described (1). Each set of maneuvers is called a cycle. Cycles are repeated until looping prevents any further forward movement and the depth of maximal insertion is reached. In the study, depth of maximal insertion 1 will be defined as a lack of forward movement after 3 consecutive cycles. When the depth of maximal insertion 1 has been reached, a small mark will be made on the wall of the small bowel by sucking mucosa into the enteroscope (ie. suction mark) or using biopsy forceps to create a 3 mm disruption in the mucosa. A virtual mark will also be made on the endoscopy video. Those randomized to the stiffening wire will insert the wire and attempt to proceed deeper. The technique for each cycle is the same as in step 3 and does not change with the presence of the wire. Those randomized to no stiffening wire will attempt to proceed deeper using standard technique. The procedure will continue until there is no forward movement after 3 consecutive cycles. If the enteroscope was able to proceed past depth of maximal insertion 1, a suction/biopsy forceps mark will be made and a virtual mark recorded on the endoscopy video to denote depth of maximal insertion 2. If the enteroscope was not able to proceed past depth of maximal insertion 1, no further marks will be made. On withdrawal of the enteroscope, care will be taken by the endoscopist to ensure any suction/biopsy forceps marks are clearly visible on the video.

Official Title
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A Randomized Clinical Trial of a Novel Stiffening Wire to Increase Depth of Insertion During Double and Single Balloon Enteroscopy

Conditions
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Small Intestine Problem

Intervention / Treatment
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* Device: Stiffening wire
* Device: Standard technique


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient undergoing antegrade DBE/SBE. Exclusion Criteria: Age < 18 Prior surgery involving resection of the esophagus, stomach, or small bowel Suspected stricture or mass in any part of the gastrointestinal tract Failure to obtain informed consent from the patient or substitute decision maker Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stiffening wire<br>A stiffening wire inserted into the instrument channel of the double/single balloon enteroscope will be used. | Device: Stiffening wire<br>* The stiffening wire will be inserted into the double/single balloon enteroscope.<br>|
| Active Comparator: Standard technique<br>The double/single balloon enteroscope will be used without the stiffening wire as per standard technique. | Device: Standard technique<br>* The double/single balloon enteroscope will be used without the stiffening wire as per standard technique.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distance gained beyond depth of maximal insertion 1 | Defined as the distance between depth of maximal insertion 1 and depth of maximal insertion 2. In cases where there is no depth of maximal insertion 2, a value of zero will be assigned. Distance will be measured using the fold counting method as follows: distance = # fold x 0.904 cm/fold. | Measured once at the time of endoscopy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final depth of insertion | Defined as the distance between depth of maximal insertion 2 (or depth of maximal insertion 1 if primary outcome = 0) and the pylorus. Distance will be measured using the fold counting method. | Measured once at the time of endoscopy | 
| Small bowel diagnostic rate | Small bowel diagnosis (dichotomous variable, yes/no) is defined as the visualization of a small bowel abnormality, such as an angioectasia, Crohn's disease, stricture, polyp, mass, or foreign body). Red spots are not included. | Measured once at the time of endoscopy | 
| Small bowel intervention rate | Small bowel therapeutics (dichotomous variable, yes/no) is defined as the application of endoscopic intervention to a small bowel abnormality, such as biopsy of a polyp/mass/ulcer, APC, dilation, polypectomy, or foreign body retrieval. | Measured once at the time of endoscopy | 
| Patient comfort survey | a. To be completed after the procedure in the recovery room using a visual analogue scale (1=no pain, 10=severe pain). Patients will be assessed for intraprocedural and postprocedural pain. | Measured once at the time of endoscopy | 
| Serious Adverse events | Perforation, bleeding requiring blood transfusion or hospital admission, pancreatitis, aspiration, significant hypotension (systolic blood pressure < 80 mmHg), hypoxia (oxygen saturation < 85%), or bradycardia (heart rate < 45 beats per minute). Assessed on day 0 and 7. | Measured once at the time of endoscopy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double-balloon enteroscopy