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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Bowel Preparations for Colonoscopy in SCI

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Drug: Neostigmine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: SCI MoviPrep® (without NG)<br>(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]) | |
| No Intervention: SCI PIEE (without NG)<br>(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)>=50ml/min) pulsed irrigation enhanced evacuation [PIEE] (without neostigmine plus glycopyrrolate [NG]) | |
| No Intervention: Control MoviPrep® only<br>(Control, glomerular filtration rate (GFR)>=50ml/min) low-volume polyethylene glycol-electrolyte lavage with ascorbic acid (MoviPrep®) only (no NG) | |
| No Intervention: Control PIEE only<br>(Control, glomerular filtration rate (GFR)>=50ml/min), pulsed irrigation enhanced evacuation (PIEE) only (no NG) | |
| Experimental: SCI MoviPrep® (with NG)<br>(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]) | Drug: Neostigmine<br>* Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established<br>|
| Experimental: SCI PIEE (with NG)<br>(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)>=50ml/min) pulsed irrigation enhanced evacuation (PIEE) (with neostigmine plus glycopyrrolate [NG]) | Drug: Neostigmine<br>* Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Bowel Preparation | 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. | 1-2 days following intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polyp Detection | The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation. | Time of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Efficacy, Colonoscopy, PIEE, MoviPrep, Neostigmine, Glycopyrrolate