Intranasal Administration of a Prokinetic for Bowel Evacuation in Persons With SCI (IN NEO)
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.
Drug: IN NEO
Drug: IN NEO + IN Glycopyrrolate
Drug: IV Visit
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intranasal Administration of Neostigmine and Glycopyrrolate for Bowel Evacuation|
- Bowel evacuation [ Time Frame: <60 min ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2012|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Drug: IN NEO
20 mg Neostigmine via intranasal and sublingual administrationDrug: IN NEO
40 mg Neostigmine via intranasal administrationDrug: IN NEO
60 mg Neostigmine via intranasal administrationDrug: IN NEO + IN Glycopyrrolate
Intranasal or sublingual Neostigmine (at effective dose: 20, 40, or 60 mg) + 4-12 mg intranasal or sublingual GlycopyyrolateDrug: IV Visit
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00855283
|United States, New York|
|VA Medical Center, Bronx|
|Bronx, New York, United States, 10468|
|Principal Investigator:||Mark A. Korsten, MD||VA Medical Center, Bronx|