Clinical trial NCT00745095
Conditions: Spinal Cord Injury
Keywords: Safety Efficacy Colonoscopy PIEE MoviPrep Neostigmine Glycopyrrolate
Sponsor: US Department of Veterans Affairs
Start date: 2009-03-01; Completion date: 2013-05-01
Enrollment: 360 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

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.

Arms: arm 1: (Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\<=50ml/min and SCI, GFR\>=50ml/min) low-volume polyethylene glycol-electrolyte lavage with ascorbic acid \[MoviPrep®\] (without neostigmine plus glycopyrrolate \[NG\]) arm 2: (Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\>=50ml/min) pulsed irrigation enhanced evacuation \[PIEE\] (without neostigmine plus glycopyrrolate \[NG\]) arm 3: (Control, glomerular filtration rate (GFR)\>=50ml/min) low-volume polyethylene glycol-electrolyte lavage with ascorbic acid (MoviPrep®) only (no NG) arm 4: (Control, glomerular filtration rate (GFR)\>=50ml/min), pulsed irrigation enhanced evacuation (PIEE) only (no NG) arm 5: (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 \[NG\]) arm 6: (Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\>=50ml/min) pulsed irrigation enhanced evacuation (PIEE) (with neostigmine plus glycopyrrolate \[NG\])
Interventions: intervention 1: Neostigmine
Intervention descriptions: intervention 1: Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established

Protocol documents: