Spinal Cord Injury
Conditions
Keywords
Safety, Efficacy, Colonoscopy, PIEE, MoviPrep, Neostigmine, Glycopyrrolate
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.
Interventions
DRUGNeostigmine
Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Bowel Preparation | 1-2 days following intervention | 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
| Measure | Time frame | Description |
|---|---|---|
| Polyp Detection | Time of Study | The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SCI MoviPrep® (Without NG) (SCI, GFR\<=50ml/min and GFR\>=50ml/min) MoviPrep® (without NG) | 14 |
| SCI MoviPrep® (With NG) (SCI, GFR\<=50ml/min and GFR\>=50ml/min) MoviPrep® (without NG)
Neostigmine: Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established | 13 |
| SCI PIEE (Without NG) (SCI, GFR\>=50ml/min) PIEE ( without NG) | 12 |
| SCI PIEE (With NG) (SCI, GFR\>=50ml/min) PIEE (with NG)
Neostigmine: Neostigmine will be administered in 20, 40, and 60mg doses until an individualized dose-response relationship is established | 12 |
| Control MoviPrep® Only (Control, GFR\>=50ml/min) MoviPrep® only (no NG) | 28 |
| Control PIEE Only (Control, GFR\>=50ml/min) PIEE only (no NG) | 27 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Declined to participate | 1 | 0 | 0 | 0 | 92 | 95 |
| Overall Study | Ineligible due to GFR criteria | 0 | 2 | 3 | 3 | 30 | 28 |
Baseline characteristics
| Characteristic | SCI MoviPrep® (Without NG) | SCI MoviPrep® (With NG) | SCI PIEE (Without NG) | SCI PIEE (With NG) | Control MoviPrep® Only | Control PIEE Only | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 8 | 65 years STANDARD_DEVIATION 6 | 61 years STANDARD_DEVIATION 11 | 58 years STANDARD_DEVIATION 5 | 58 years STANDARD_DEVIATION 10 | 60 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 14 participants | 13 participants | 12 participants | 12 participants | 28 participants | 27 participants | 106 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 11 Participants | 11 Participants | 26 Participants | 25 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 14 | 7 / 13 | 4 / 12 | 10 / 12 | 4 / 28 | 20 / 27 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 0 / 12 | 0 / 12 | 1 / 28 | 1 / 27 |
Outcome results
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.
Time frame: 1-2 days following intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCI MoviPrep® (Without NG) | Quality of Bowel Preparation | 3.4 units on a scale | Standard Deviation 1.6 |
| SCI MoviPrep® (With NG) | Quality of Bowel Preparation | 2.5 units on a scale | Standard Deviation 2.4 |
| SCI PIEE (Without NG) | Quality of Bowel Preparation | 3.6 units on a scale | Standard Deviation 3.1 |
| SCI PIEE (With NG) | Quality of Bowel Preparation | 7.4 units on a scale | Standard Deviation 5 |
| Control MoviPrep® Only | Quality of Bowel Preparation | 1.8 units on a scale | Standard Deviation 1.9 |
| Control PIEE Only | Quality of Bowel Preparation | 6.9 units on a scale | Standard Deviation 4.8 |
Secondary
Polyp Detection
The number of polyps detected during colonoscopic procedures were recorded and compared to each bowel cleansing preparation.
Time frame: Time of Study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCI MoviPrep® (Without NG) | Polyp Detection | 1.3 Number of polyps detected (numerical) | Standard Deviation 1.7 |
| SCI MoviPrep® (With NG) | Polyp Detection | 1.3 Number of polyps detected (numerical) | Standard Deviation 1.5 |
| SCI PIEE (Without NG) | Polyp Detection | 0.4 Number of polyps detected (numerical) | Standard Deviation 1.2 |
| SCI PIEE (With NG) | Polyp Detection | 0.5 Number of polyps detected (numerical) | Standard Deviation 1.2 |
| Control MoviPrep® Only | Polyp Detection | 0.9 Number of polyps detected (numerical) | Standard Deviation 1 |
| Control PIEE Only | Polyp Detection | 0.3 Number of polyps detected (numerical) | Standard Deviation 0.8 |