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

NCT ID: NCT00745095

Last Updated: 2014-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2013-05-31

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.

Conditions

Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

SCI MoviPrep® (without NG)

(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 \[NG\])

Group Type: NO_INTERVENTION

No interventions assigned to this group

SCI PIEE (without NG)

(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\>=50ml/min) pulsed irrigation enhanced evacuation \[PIEE\] (without neostigmine plus glycopyrrolate \[NG\])

Group Type: NO_INTERVENTION

No interventions assigned to this group

Control MoviPrep® only

(Control, glomerular filtration rate (GFR)\>=50ml/min) low-volume polyethylene glycol-electrolyte lavage with ascorbic acid (MoviPrep®) only (no NG)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Control PIEE only

(Control, glomerular filtration rate (GFR)\>=50ml/min), pulsed irrigation enhanced evacuation (PIEE) only (no NG)

Group Type: NO_INTERVENTION

No interventions assigned to this group

SCI MoviPrep® (with NG)

(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 \[NG\])

Group Type: EXPERIMENTAL

Neostigmine

Intervention Type: DRUG

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

SCI PIEE (with NG)

(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)\>=50ml/min) pulsed irrigation enhanced evacuation (PIEE) (with neostigmine plus glycopyrrolate \[NG\])

Group Type: EXPERIMENTAL

Neostigmine

Intervention Type: DRUG

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

Interventions

Neostigmine

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark A. Korsten, MD

Role: PRINCIPAL_INVESTIGATOR

VA Medical Center, Bronx

Locations

VA Medical Center, Bronx

The Bronx, New York, United States

Countries

United States

References

Lyons BL, Korsten MA, Spungen AM, Radulovic M, Rosman AS, Hunt K, Galea MD, Kornfeld SD, Yen C, Bauman WA. Comparison between pulsed irrigation enhanced evacuation and polyethylene glycol-electrolyte lavage solution for bowel preparation prior to elective colonoscopy in veterans with spinal cord injury. J Spinal Cord Med. 2015 Nov;38(6):805-11. doi: 10.1179/2045772314Y.0000000256. Epub 2014 Aug 6.

Reference Type: DERIVED

PMID: 25096918 (View on PubMed)

Other Identifiers

KOR-09-10

Identifier Type: OTHER

Identifier Source: secondary_id

A6428-R

Identifier Type: -

Identifier Source: org_study_id