Use of a Prokinetic Agent as an Adjunct to Thrice Weekly Bowel Care After SCI
Condition: Spinal Cord Injuries; Constipation; Neurogenic Bowel
MeSH terms: Neurogenic Bowel; Spinal Cord Injuries; Constipation
Study type: Interventional
Phase: Phase 1

Summary: 
      To measure a baseline for each subject, an abdominal x-ray (KUB) was performed, the SCI Bowel
      Survey and Treatment Satisfaction Questionnaire (TSQM) were administered and the subject's
      weight determined. After all the baseline measurements were acquired, the subjects underwent
      transdermal screening with hair epilation to test their response to transdermal
      administration of NEO (0.07mg/kg) and GLY (0.014mg/kg). All subjects had a positive response
      (bowel movement within 60 minutes of drug administration) and received five more cycles of
      bowel care for two weeks. All subjects reported bowel evacuation during each session and some
      reported side effects like slight dry mouth, eye twitching, and cramping. These side effects
      lasted approximately 20-30 minutes in duration and there were no clinically significant
      changes in cardiopulmonary vital signs. Six subjects after completing two weeks of bowel care
      had an abdominal x-ray (KUB) done. Also, they were weighted and reassessed using the TSQM and
      bowel survey.
    

Detailed description: 
      Part 1: IV Screening Twenty subjects with chronic SCI (>1 year) and difficulty with
      evacuation (DWE) managed by a regular, thrice weekly bowel care (BC) routines will be
      recruited for study participation. In order to determine eligibility for the study, the
      subject will have to undergo an IV screening to test whether or not they are responsive to
      the drug treatment (neostigmine-glycopyrrolate). Subjects will receive the following dose:
      0.03mg/kg neostigmine (NEO) and 0.006mg/kg glycopyrrolate (GLY). If the subject responds
      (bowel movement) to the IV treatment, they will be allowed to continue on to part 2 of the
      study. If patient does not have a successful bowel movement, then they will be considered a
      non-responder and study participation will be discontinued. Study procedures can be found in
      table below.

      Part 2: Baseline and Iontophoresis Screening Once eligibility has been determined, and
      subject consent has been obtained, each subject will undergo 1 week of baseline observation.
      An abdominal x-ray (KUB) will be performed, the SCI Bowel Survey and Treatment Satisfaction
      Questionnaire (TSQM) will be administered, and the subject's weight determined. Each subject
      will continue with regular bowel care and after 1 week, all of the baseline measurements
      (KUB, weight and surveys) will be repeated. This will be followed by an additional screening
      visit during which we will concomitantly administer transcutaneous NEO and GLY via
      iontophoresis (ION). Subjects will receive the following dose: 0.07mg/kg NEO and 0.014mg/kg
      GLY. This visit will be scheduled on a BC day. All procedures will take place in the "Blue
      Room" located in the SCI ward. As part of the setup, subjects will be instrumented with blood
      pressure cuff; intravenous access will be obtained at a peripheral vein (if one is not
      available), as a precautionary measure, since the drug will be administered via an
      Iontophoresis transdermal patch. Heart rate will be continuously monitored throughout the
      procedure through finger oximetry. Symptoms will be assessed every 5 minutes for 60 minutes.
      Impulse Oscillometry system (IOS) will be used to measure the effect of the medication on
      airway obstruction. If the subject has a positive response (bowel movement within 60 minutes
      of drug administration) he/she will be eligible to continue to the third study phase. If the
      subject does not respond, the subject will be considered a non-responder and study
      participation will be discontinued. We expect that about 1/3rd of the subjects will be
      non-responders, or will be lost to attrition; therefore, we are prepared to over-recruit by 5
      subjects in order to ensure that at least 15 subjects will be eligible to complete the second
      part of the study.

      The study will be stopped once the patient experiences a bowel movement within 30 minutes of
      administering ION NEO because the protocol objective will have been achieved. If the patient
      should experience cardiopulmonary side effects when receiving the ION NEO that are not
      effectively reversed by the ION GLY, the study will be stopped. In addition, the study
      investigators reserve the right to stop the study should they have any other safety concerns.

      Part 3: 2 Week Treatment Each subject will be assessed for their perception of their current
      BC routine using the Treatment Satisfaction Questionnaire for Medication (TSQM-Appendix 1),
      and their bowel habits using the bowel survey (Appendix 2).The subject will then be asked to
      continue with their normal BC routine for two weeks, with the exception that NEO and GLY will
      be administered at the beginning of each BC session as an adjunct to each subject's normal
      routine. Subjects will be asked to come to the JJPVAMC for each BC session. Each BC session
      will be documented by a study team member including the time needed to complete BC, methods
      used (i.e. number of enemas used, oral laxatives, suppositories, digital stimulation,
      abdominal massage) and the quality and completeness of the bowel movement. Heart rate,
      oxygenation and blood pressure will be monitored continuously. Subjects will be weighed at
      baseline, once after each week of treatment and once at the post treatment follow-up visit.
      After two weeks of treatment, each subject will undergo a final KUB and be reassessed for
      their perception of the BC routine for the past two weeks using the TSQM and their bowel
      habits (bowel survey).

      *During the treatment period (part 3), monitoring will take place for the first hour after
      administration of study medications. However, bowel care will continue for as long as is
      clinically indicated. Additional techniques for bowel care (i.e. enema, suppository, digital
      stimulation, etc.) will be used in coordination with SCI nurses to promote bowel evacuation
      for subjects who do not respond.

      **An IV line will be inserted during all study visits. Study medication will be administered
      intravenously during Part 1 only. An IV line will be available however through all sessions
      involving study medication for safety purposes in the case that an antidote needs to be
      administered
    

Intervention name(s): Neostigmine and Glycopyrrolate; Iontophoresis
Intervention type(s): Drug; Device
Intervention description(s): Intravenous followed by transdermal administration of the two drug combination.; Application of direct current to skin using an FDA-approved device
Other intervention name(s): I-Box
Intervention MeSH terms: Glycopyrrolate; Neostigmine
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Intervention model description: Single group interventional study with brief crossover of subjects into the placebo group
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Neostigmine; Glycopyrrolate; Transdermal; Intravenous; Constipation; Bowel care; Neurogenic bowel