The MOTOR-CD Trial
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional

Summary: 
      Both single-balloon enteroscopy (SBE) and novel motorized spiral enteroscopy (NMSE) are
      effective techniques for small bowel endoscopy in suspected Crohn's disease (CD). Small bowel
      endoscopy is indicated for confirming diagnosis when CD is suspected based on clinical
      features along with cross-sectional small bowel imaging (computed tomography
      enterography/enteroclysis: CTE or magnetic resonance enterography/enteroclysis: MRE) or
      capsule endoscopy (CE). It not only helps in diagnosing CD, but it also helps in excluding
      CD, diagnosing alternate conditions and taking a surgical decision if a tight stricture is
      found. The pilot study done by the investigators in 177 suspected CD patients (37.2% female,
      7-75 years) undergoing total 201 device assisted enteroscopy (DAE) showed that NMSE scores
      over SBE with regards to small bowel evaluation with complete small bowel coverage and
      shorter procedure time. The investigators aim to validate this findings by comparing
      technical performance and diagnostic yield between NMSE (Olympus Medical, Tokyo, Japan) and
      SBE (Olympus Medical Systems Corporation, Tokyo, Japan) for small bowel evaluation.
      Additionally the investigators plan to compare depth of insertion, total enteroscopy rates,
      procedure time, adverse event rates between the two modalities.

      To date, no study has compared both modalities in suspected Crohn's disease (CD) requiring
      small bowel evaluation in a randomized manner. Hence the investigators intend to perform a
      randomized controlled study based on these preliminary finding with appropriate matching and
      parallel study design in larger numbers.
    

Detailed description: 
      Study design

      Study population Consecutive patients with suspected Crohn's disease requiring small bowel
      endoscopy based on abnormal imaging or capsule endoscopy shall be recruited.

      Study settings:

      The proposed study would be conducted in a high volume tertiary GI centre (Asian Institute of
      Gastroenterology) performing nearly more than 500 SBE/NMSE procedures per year with an well
      established inflammatory bowel disease (IBD) registry with more than 7000 IBD patients under
      follow up.

      The study is approved by the institutional review boards and ethics committee. Written
      informed consent would be taken from each participants and the study would conform to the
      1975 Declaration of Helsinki ethical guidelines.

      Data collection A survey administration software (google forms) would be used to collect the
      participant data [age, sex, comorbidities, clinical features, smoking status, history of
      intestinal resection, type of DAE, indication of DAE, CT/MRE location and characteristic of
      lesions, capsule endoscopy findings, depth of insertion, time taken for the procedure, total
      enteroscopy rates, enteroscopy finding details, cause of failure if any, DAE findings,
      histopathology details, impact on management, adverse events, hospital stay and any
      therapeutic procedure performed e.g. endoscopic balloon dilation (EBD) with details].
      Follow-up details for newly diagnosed CD cases would be collected via physical visit or
      telephonic communication.

      Technique and instruments Single balloon enteroscopy: All SBE procedures will be performed
      with single balloon video-enteroscope (Olympus Medical Systems, Tokyo, Japan) under monitored
      anaesthesia (deep sedation with propofol). Initially antegrade/retrograde enteroscopy would
      be performed based on anticipated location in CT failing which enteroscopy would be done from
      opposite route to reach the lesion. If the desired lesion is not reached via
      antegrade/retrograde route, hemoclips would be applied or tattooing would be done followed by
      enteroscopy from opposite direction on the same day under the same anaesthesia using the same
      overtube. Fluoroscopy would be used in select cases with anticipated therapeutic procedure.
      All the procedures were done after minimum of 8 hours of fasting and bowel preparation was
      given with 4 litres of polyethylene glycol (PEG) for all. Duration of procedure would be
      calculated from the time of introduction of the enteroscope to time of removal. The depth of
      insertion would be measured using the push and pull technique. If the desired lesion is not
      reached by a single route and was deemed possible to reach by the other route, the area of
      maximal insertion shall be marked by India ink tattooing or hemoclip application followed by
      completion of bidirectional enteroscopy on the same or next working day.

      Novel motorized spiral enteroscopy: All the NMSE (Olympus Medical Systems Corporation, Tokyo,
      Japan) procedures would be performed under general anaesthesia with nasotracheal intubation
      under fluoroscopic guidance. Four litres of PEG was given to all patients with at least 8
      hours of fasting prior to NMSE. Initially antegrade enteroscopy would be performed failing
      which retrograde enteroscopy would be done to reach the lesion. If the desired lesion is not
      reached via antegrade route, hemoclips would be applied or tattooing would be done followed
      by retrograde enteroscopy on the same day under the same anesthesia using the same overtube.
      The time of procedure will be calculated from insertion of NMSE to its withdrawal. The depth
      of insertion would be measured by sequential withdrawal technique as described earlier.

      All the enteroscopy procedures were performed by four small bowel endoscopists all of whom
      have performed at least 200 deep enteroscopy. At least 8 biopsies were taken from area of
      interest during DAE and sent for histopathological analysis. In selected cases, additional
      samples were sent for detection of tubercular bacilli using mycobacterium tuberculosis
      (MTB)-polymerase chain reaction (PCR) if clinically tuberculosis was considered as
      differential diagnosis. Histopathological findings were recorded under the following headings
      for diagnosing CD: chronic inflammation, architectural distortion and presence of granulomas.

      Definitions:

      Technical success shall be defined as enteroscope introduction beyond duodenojejunal (DJ)
      flexure or ileocecal valve via antegrade and retrograde route respectively. The diagnostic
      yield with DAE shall be defined as the percentage of procedures which confirmed/excluded
      lesions found on prior cross-sectional imaging (CTE/MRE) or found new/alternate diagnosis
      explaining the clinical condition. Depth of maximal insertion (DMI) will be defined as the
      point beyond which DAE advancement was not feasible. Major adverse events are perforation,
      pancreatitis, bleeding requiring transfusion or procedure related hospitalization. Minor
      adverse events are superficial mucosal injury, self limiting sore throat/nausea/vomiting,
      minor bleeding (without need for blood transfusion) or pain abdomen (not requiring hospital
      admission). Total enteroscopy will be defined as examination of small bowel from DJ flexure
      to ileocecal valve. Total enteroscopy would be achieved by either uni-directional (antegrade
      or retrograde route) or bi-directional enteroscopy (using both antegrade and retrograde
      route). The histopathological diagnosis of CD will be confirmed if non-caseating
      micro-granulomas are found with either of both of the other two histological features
      (chronic inflammation and architectural distortion) and alternate diagnosis like small bowel
      tuberculosis is ruled out based on clinical, radiologic and other relevant findings. Presence
      of both chronic inflammation and architectural distortion, non-caseating granuloma/chronic
      inflammation/ architectural distortion alone will be considered suggestive of CD in the
      appropriate clinical settings.

      Sample size

      Based on the pilot study by the investigators, diagnostic yield for deep enteroscopy with
      NMSE and SBE (97.8% and 83.2% respectively, the estimated sample size is total 124 (62 in
      each group) keeping type 1 error as 0.05 and power as 80%.

      Randomisation

      Randomisation will be done based on web based randomisation services

      Timeline: 2 years Recruitment of 124 suspected CD patients requiring small bowel evaluation
      over maximum 2 years.

      Patient privacy An organised database for the purpose of this study will be formed based on
      google form with anonymised data set (i.e. name, address, and full post code will be removed,
      together with any other information which, in conjunction with other data held by or
      disclosed to the recipient, could identify the patient) which would be entered by clinical
      research assistant.
    

Intervention name(s): Novel motorized spiral enteroscopy; Single balloon enteroscopy
Intervention type(s): Device; Device
Intervention description(s): Novel motorized spiral enteroscopy (Olympus Medical Systems Corporation, Tokyo, Japan) procedures would be performed under general anaesthesia with nasotracheal intubation under fluoroscopic guidance. Four litres of PEG was given to all patients with at least 8 hours of fasting prior to NMSE. Initially antegrade enteroscopy would be performed failing which retrograde enteroscopy would be done to reach the lesion. If the desired lesion is not reached via antegrade/retrograde route, hemoclips would be applied or tattooing would be done followed by enteroscopy from opposite direction on the same day under the same anesthesia using the same overtube. The time of procedure will be calculated from insertion of NMSE to its withdrawal. The depth of insertion would be measured by sequential withdrawal technique.; Single balloon enteroscopy will be performed with single balloon video-enteroscope (Olympus Medical Systems, Tokyo, Japan) under monitored anaesthesia (deep sedation with propofol). Initially antegrade/retrograde enteroscopy would be performed based on pre-procedure localization failing which enteroscopy would be done from opposite route to reach the lesion. Hemoclips would be applied or tattooing would be done followed by enteroscopy from opposite direction on the same day under the same anaesthesia using the same overtube. Duration of procedure would be calculated from the time of introduction of the enteroscope to time of removal. The depth of insertion would be measured using the push and pull technique.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Device-assisted enteroscopy; Single balloon enteroscopy; Novel motorized spiral enteroscopy; total enteroscopy