Intranasal Administration of a Prokinetic for Bowel Evacuation in Persons With SCI
Condition: SCI
Study type: Interventional
Phase: Phase 2

Summary: 
      DWE (difficulty with evacuation) is a common and an important quality of life issue after
      spinal cord injury. Not only is the management DWE time-consuming and unpleasant, but the
      results are often suboptimal in terms of complications such as incontinence and impaction.
      Bowel care regimens after spinal cord injury have not changed in any significant fashion in
      many years. The usual strategies for attaining bowel evacuation involve dietary manipulation
      (e.g., high fiber diets and hydration), thrice weekly laxative administration (senna and
      cascara) and thrice weekly anorectal instillation of cathartics (enemas and suppositories).
      Bowel care can be quite time consuming (greater than 2 hours in many instances) and may also
      require extensive nursing care. Finally, incomplete evacuation could contribute to fecal
      incontinence that has significant morbidity in these patients.

      In preliminary studies performed at the JJPVAMC, IV, IM, and subcutaneous injection of
      neostigmine combined with glycopyrrolate were demonstrated to be highly effective to promote
      bowel evacuation in the SCI population. In an effort to provide a more realistic
      administration of this procedure, we propose to test the intranasal spray injection of
      neostigmine and glycopyrrolate for safety and efficacy.
    

Detailed description: 
      We have been studying the effects of spinal cord injury on the bowel for over ten years. Our
      data suggests that one of the fundamental consequences of spinal cord injury is a slowing of
      intestinal peristaltic activity, most likely as a result of down regulation of
      parasympathetic neural pathways. Furthermore, measures that increase parasympathetic
      stimulation to the bowel result in bowel evacuation and improve bowel care. In this respect,
      significant acute effects have been demonstrated after the intravenous administration of the
      cholinergic agent neostigmine (Am J Gastro 100:1560-5, 2005). Long term efficacy has also
      been shown using intramuscular administration of neostigmine (Gastro 128:P258, 2005).
      Subcutaneous administration of neostigmine is in progress at this time. Bowel evacuation also
      is facilitated by subcutaneous administration but often requires a second dose (30 minutes
      after the first). This observation is likely due to a decreased rate of absorption from this
      tissue compartment and a correspondingly lower peak level of neostigmine (vide infra). Given
      the potential cardiopulmonary toxicity of neostigmine (bradycardia and bronchoconstriction),
      neostigmine was administered in these studies in combination with the anticholinergic agent
      glycopyrrolate. We have reported that the latter selectively blocks the cardiopulmonary side
      effects of neostigmine without significantly decreasing the prokinetic peristaltic response.
      In summary, our data to date indicates that the combined administration of neostigmine and
      glycopyrrolate is safe after spinal cord damage and it results in predicable and prompt bowel
      evacuation.
    

Intervention name(s): IN NEO; IN NEO; IN NEO; IN NEO + IN Glycopyrrolate; IV Visit
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 20 mg Neostigmine via intranasal and sublingual administration; 40 mg Neostigmine via intranasal administration; 60 mg Neostigmine via intranasal administration; Intranasal or sublingual Neostigmine (at effective dose: 20, 40, or 60 mg) + 4-12 mg intranasal or sublingual Glycopyyrolate; 2mg NEO and .4mg GLY given intravenously to see if the subject responds to the intervention. If they respond, then they will proceed to the IN portion of the study.
Intervention MeSH terms: Glycopyrrolate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment