Efficacy and Safety of Standard Oral Colonoscopic Preparations With or Without Neostigmine Compared to Pulse-Irrigation Colonic Lavage

Phase 4

Completed

Conditions: Spinal Cord Injury

Interventions: Drug: Neostigmine

Registration Number: NCT00745095

Lead Sponsor: US Department of Veterans Affairs

Brief 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 360

Inclusion Criteria

SCI and able-bodied patients with clinical indication for a colonoscopic examination

Exclusion Criteria

Able-bodied patients with a GFR 50ml/min.
SCI and able-bodied patients who are not candidates for elective colonoscopy (i.e., those with recent myocardial infarction, terminal illness, etc.)
SCI and able-bodied patients who have a contraindication to PEG and/or ascorbic acid administration (i.e., those with colonic obstruction, etc.)
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)
SCI and able-bodied patients with a history of bradyarrhythmia, active coronary artery disease or asthma will also be excluded from receiving neostigmine/glycopyrrolate
Known hypersensitivity to neostigmine or glycopyrrolate
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.)
Lactating/nursing females
SCI patients with known adverse reactions to per-rectal colonic lavage.
SCI patients with a serum sodium <130 mM.

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
SCI PIEE (with NG)	Neostigmine	(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\>=50ml/min) pulsed irrigation enhanced evacuation (PIEE) (with neostigmine plus glycopyrrolate \[NG\])
SCI MoviPrep® (with NG)	Neostigmine	(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\<=50ml/min and SCI GFR\>=50ml/min) low-volume polyethylene glycol-electrolyte lavage with ascorbic acid \[MoviPrep®\] (with neostigmine plus glycopyrrolate \[NG\])

Primary Outcome Measures

Name	Time	Method
Quality of Bowel Preparation	1-2 days following intervention	The quality of bowel preparation was determined by using the Ottawa Scale for bowel Evacuation. The range of this score is from 0 (perfectly clean and dry colon) to 14 ( a colon filled with stool and liquid). The right, mid and rectosigmoid colon were independently rated from 0-4 and fluid quality of entire colon was recorded with an additional score of 0-2. The total Ottawa Score is calculated by the sum of the independent scores of all three sections of the colon plus the fluid content.

Secondary Outcome Measures

Name	Time	Method
Polyp Detection	Time of Study	The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation.