Efficacy and Safety of Standard Oral Colonoscopic Preparations With or Without Neostigmine Compared to Pulse-Irrigation Colonic Lavage
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries
Intervention: Neostigmine
Intervention description: Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established
Intervention MeSH terms: Neostigmine
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 360.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Safety; Efficacy; Colonoscopy; PIEE; MoviPrep; Neostigmine; Glycopyrrolate

Summary:

      The annual incidence of colorectal cancer in the US during 2005 was approximately 150,000
      cases and this neoplasm claimed 56,000 lives (American Cancer Society). Detection (and
      removal) of colonic polyps is now the central strategy in reducing the risk of colon cancer.
      Thus, failure to detect and remove small cancers and polyps can have dire consequences.
      Although it has not been shown that persons with spinal cord injury (SCI) have an increased
      risk of this disease, there is no reason to assume that the incidence after SCI would be less
      than that of the general population.

      Colonoscopy would appear to be a better approach to colon cancer screening after SCI but may
      also be unreliable if bowel evacuation is unsatisfactory for complete large bowel
      visualization. Poor colonoscopic visualization is a major concern in persons with SCI because
      they have long-standing difficulty with evacuation (DWE) and might not respond in a
      predictable or satisfactory manner to the conventional bowel preparations used for
      colonoscopy. Furthermore, to the extent that bowel preparation for colonoscopy is
      unsatisfactory in persons with SCI, the putative benefits of colonoscopy in reducing colon
      cancer mortality may not be realized.

      In the absence of effective regimens for bowel preparation in persons with SCI, we suspect
      that the documented benefits of screening colonoscopy in the able-bodied may not generalize
      to persons with SCI. Regardless, these observations support the need for improved bowel
      preparation approaches in persons with SCI. One such approach might involve the adjunctive
      administration of prokinetic drugs to standard practices. A prokinetic agent that might be
      beneficial in this context is neostigmine, an anticholinesterase inhibitor with prominent
      parasympathomimetic actions (stimulation of peristalsis) on the colon. We have studied
      neostigmine extensively in persons with SCI and have shown that, when given in combination
      with glycopyrrolate, this approach to stimulate bowel evacuation is safe and effective for
      bowel evacuation.
    

Eligibility criteria:

        Inclusion Criteria:

        1. SCI and able-bodied patients with clinical indication for a colonoscopic examination

        Exclusion Criteria:

          1. Able-bodied patients with a GFR 50ml/min.

          2. SCI and able-bodied patients who are not candidates for elective colonoscopy (i.e.,
             those with recent myocardial infarction, terminal illness, etc.)

          3. SCI and able-bodied patients who have a contraindication to PEG and/or ascorbic acid
             administration (i.e., those with colonic obstruction, etc.)

          4. SCI and able-bodied patients who have a contraindication for magnesium citrate (i.e.,
             those with poor renal function, class 2 or greater symptomatic heart failure, ascites)

          5. SCI and able-bodied patients with a history of bradyarrhythmia, active coronary artery
             disease or asthma will also be excluded from receiving neostigmine/glycopyrrolate

          6. Known hypersensitivity to neostigmine or glycopyrrolate

          7. Potential for pregnancy. Women who are sexually active and of childbearing potential
             (i.e. not surgically sterile or at least 2 years postmenopausal) must have negative
             serum pregnancy test.)

          8. Lactating/nursing females

          9. SCI patients with known adverse reactions to per-rectal colonic lavage.

         10. SCI patients with a serum sodium <130 mM.