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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00745095
First received: September 2, 2008
Last updated: July 2, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Spinal Cord Injury
Drug: Neostigmine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Efficacy and Safety of Bowel Preparations for Colonoscopy in SCI

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Quality of Bowel Preparation [ Time Frame: 1-2 days following intervention ] [ Designated as safety issue: No ]
    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:
  • Polyp Detection [ Time Frame: Time of Study ] [ Designated as safety issue: No ]
    The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation.


Enrollment: 360
Study Start Date: March 2009
Study Completion Date: May 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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])
No Intervention: SCI PIEE (without NG)
(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
(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
(Control, glomerular filtration rate (GFR)>=50ml/min), pulsed irrigation enhanced evacuation (PIEE) only (no NG)
Experimental: 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])
Drug: Neostigmine
Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established
Experimental: SCI PIEE (with NG)
(Spinal Cord Injury (SCI), glomerular filtration rate (GFR)>=50ml/min) pulsed irrigation enhanced evacuation (PIEE) (with neostigmine plus glycopyrrolate [NG])
Drug: Neostigmine
Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00745095

Locations
United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468
Sponsors and Collaborators
Investigators
Principal Investigator: Mark A. Korsten, MD VA Medical Center, Bronx
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00745095     History of Changes
Other Study ID Numbers: A6428-R, KOR-09-10
Study First Received: September 2, 2008
Results First Received: April 18, 2014
Last Updated: July 2, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Safety
Efficacy
Colonoscopy
PIEE
MoviPrep
Neostigmine
Glycopyrrolate

Additional relevant MeSH terms:
Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Glycopyrrolate
Neostigmine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014