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

Spinal Cord Injury Clinical Trial

Official title:

Efficacy and Safety of Bowel Preparations for Colonoscopy in SCI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00745095
• Other study ID #: A6428-R
• Secondary ID: KOR-09-10
• Status: Completed
• Phase: Phase 4
• First received: September 2, 2008
• Last updated: July 2, 2014
• Start date: March 2009
• Est. completion date: May 2013

Study information

• Verified date: May 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: May 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

1. Able-bodied patients with a GFR 50ml/min.

2. SCI and able-bodied patients who are not candidates for elective colonoscopy (i.e., those with recent myocardial infarction, terminal illness, etc.)

3. SCI and able-bodied patients who have a contraindication to PEG and/or ascorbic acid administration (i.e., those with colonic obstruction, etc.)

4. 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)

5. SCI and able-bodied patients with a history of bradyarrhythmia, active coronary artery disease or asthma will also be excluded from receiving neostigmine/glycopyrrolate

6. Known hypersensitivity to neostigmine or glycopyrrolate

7. 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.)

8. Lactating/nursing females

9. SCI patients with known adverse reactions to per-rectal colonic lavage.

10. SCI patients with a serum sodium <130 mM.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Drug:
• Neostigmine
Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established

Locations

Country	Name	City	State
United States	VA Medical Center, Bronx	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Polyp Detection	The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation.	Time of Study	No