Fecal Incontinence, Neurogenic Bowel
Conditions
Keywords
cecostomy, appendicostomy
Brief summary
There is a surgical procedure to help children with intractable fecal incontinence gain continence for stool through construction of a tube that connects the abdominal wall to the colon near or through the appendix. This tube allows easy administration of enema solution into the first part of the colon. Putting enema solution through that tube into the colon is called an antegrade continence enema (ACE) and has been shown to work well in helping some but not all children prevent stool accidents. The purpose of this study is to compare a large volume ACE flush using a salt water solution called normal saline with a small volume ACE flush using liquid glycerin. The aims of this study are to: 1) find the most effective dose and flush frequency of each solution needed to prevent stool accidents; 2) compare which solution given at the best dose has the least side effects and 3) to determine if administration of either of the ACE flushing solutions causes electrolyte abnormalities or affects colon health.
Detailed description
Fecal incontinence past the time of toilet training is devastating to affected children. Antegrade continence enema (ACE) therapy administered through a catheterizable stoma surgically placed in the cecum has helped children with intractable fecal incontinence attain continence for stool. There are a number of retrospective studies demonstrating the variable effectiveness rates of ACE therapy. This variability may be due to what is used to flush. There are no prospective trials evaluating the effectiveness of different flushing regimens. The catheterizable stoma used for the antegrade administration of enema solution is frequently made by bringing the appendix out through the abdominal wall or by placing a skin-level device (button) in to the cecum. ACE therapy administration through the appendix or into the cecum has the potential to cause colonic dysfunction. The effects of ACE administration on colonic mucosal health has not been investigated. This pilot study will compare a high volume normal saline (NS) flush and a low volume United States Pharmacopeia (USP) glycerin flush. The primary aims of the study are to compare which solution, given at an optimal dose and frequency, is associated with fewer side effects, while promoting the higher degree of fecal continence, and to determine if antegrade enema solution administration through an appendicostomy/cecostomy causes electrolyte abnormalities or affects gut health.
Interventions
DRUGDose Response - NS and USP Glycerin - First Intervention
This trial used a repeated measures, single subjects alternating treatments A-B-C-B'-C'-B1' withdrawal design in which all subjects were tested under all conditions and each subject acted as his or her own control. The subjects were randomly assigned to either normal saline or USP glycerin to control for order effects. Baseline data A served as the control and was obtained pre-operatively. The B-C arm evaluated dose-response relationship and was used to identify the minimum dosing volume and frequency of ACE administration of NS and USP Glycerin necessary to promote fecal continence. When the optimal dose as identified, the child continued on that dose for 2 weeks to insure treatment stability and effectiveness.
DRUGEffectiveness - NS and USP Glycerin - Second Intervention
To prevent statistical bias from subject loss due to treatment failure, each child was randomized to a second treatment sequence once they have achieved continence with minimal side effects on optimal dosing The second phase B'-C'-B1' of the study compared the two regimens at optimal dose and administration frequency. This phase was used to confirm the effectiveness of NS and USP Glycerin at optimal dosing on continence and assess side effects.
Sponsors
University of Florida
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* This study will involve twelve children ages 3 to 12 years recruited from subspecialty clinics at Nemours Children's Subspecialty Care and the Pediatric Spinal Defects Clinic in Jacksonville, Florida. * Children will be selected by purposive sampling and will include those who are scheduled to have an ACE stoma and will require regular antegrade enema administration to maintain continence.
Exclusion criteria
* Excluded will be children with preexisting electrolyte imbalance, chronic high rectal tone, quadriplegia, renal or cardiac disease, or those who require prophylactic antibiotics, cannot communicate, or have significant cognitive delay that would interfere with their ability to fully participate in the study. * Parents must have English language competency and be willing and able to participate in administration or oversight of the flushing regimen and data collection for a minimum of 20 consecutive weeks. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen | Data collection started following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days. | Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. The purpose of this outcome measure was to document the number of individuals who gained continence on NS and USP glycerin. Descriptive statistics was limited to percentage of total participants who achieved continence on each flushing regimen. Data was calculated on the last data point in the final phase for both the NS and USP glycerin flush. |
| Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin | Data collection began following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days. | Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. Descriptive statistics included mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05, calculated on the data from the last day of the completed NS and USP Glycerin phases of the study. Power analysis conducted using data from this study with α = 0.5, power of .80, correlation between two means of .598, and effect size of 1.554 estimated a sample size of 11 would be needed to minimize the risk of a Type II error to (20%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Electrolyte Abnormality | Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples | Evaluated impact of NS and USP Glycerin antegrade flush on serum electrolytes using a blood test called a Basic Metabolic Panel. Data analysis limited to percentage of subjects demonstrating any electrolyte abnormality on NS or USP glycerin. |
| Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject | Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples | Stool calprotectin was used to evaluate the impact of NS and USP Glycerin antegrade flush on colonic health. Calprotectin levels were obtained at baseline and following completion of the NS and USP Glycerin dosing phase of the study. Descriptive data analysis included mean and standard deviation for each flush regimen. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Both descriptive and inferential data analysis was calculated on the difference in calprotectin levels between samples obtained at baseline and samples obtained following the completion of the NS and USP Glycerin flush (value at completion of dosing phase - baseline value). The assumption was the length of each dosing phase was sufficient to achieve a credible active washout period and therefore levels obtained at the end of a phase reflected flushing regimen effects colonic health regardless of flush order. |
| NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence | Frequency of administration data was collected as the total number of flushes recieved over the last three days of each dosing phase for both NS and USP Glycerin and recorded as either daily (1), every other day (2), or every third day | Flush administration frequency necessary to achieve continence was recorded as a single measure per subject per flush solution obtained as the number of flushes in the last three days of each dosing phase and recorded as either daily (1), every other day (2), or every third day (3). The larger the value, the less frequent the flush, the better the clinical outcome. Dosing frequency was measured using direct observational recording completed by the parent or child. Descriptive analysis included mean, and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the data from the last day of the completed NS and USP Glycerin phases of the study. |
| Number of Participants Experiencing Vagal Symptoms With Flush | Data collection started with the first flush administered following discharge from the hospital and was collected with every subsequent flush through completion of the study, an average of 115 days. | Vagal symptoms including nausea, vomiting, sweating, dizziness, and pallor were noted by the parent. The parent was instructed to call if the child had any vagal symptoms. Documentation of any vagal symptoms was completed by the parent and child on a data-collection form at the time of occurrence. Data was analyzed as a percentage of subjects experiencing vagal symptoms during flush with NS and USP glycerin. |
| Cramping With Flush | Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin dosing phase | Cramping with flush was measured using the Wong Baker Faces Pain Rating Scale (WBFPRS). The WBFPRS has undergone extensive testing and has well established psychometrics in the pediatric population. The scale ranges from 0 (very happy without pain) to 10 (the worse pain imaginable). Each pain level is associated with a facial expression. The child is asked to choose the face that best describes his/her level of discomfort (ordinal data). The parent was instructed to call if the child had flushing regimen-associated discomfort greater than a 4 on the WBFPRS. Documentation of pain severity was completed by the parent and child on a data-collection form at the time of occurrence. Descriptive statistics including mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the last data point in the dosing phase. |
| Flush Volume | Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study | Flush volume was measured in mL/flush using a graduated cylinder and recorded by the parent or child with each flush and later calculated in mL/kg. Data derived from the last flush of the completed dosing phase of both NS and USP Glycerin were used to calculate flush volume. Descriptive analysis included mean, median, range, and standard deviation. Reported data excludes subjects who failed to gain and maintain continence on either flushing regimen. |
Countries
United States
Participant flow
Recruitment details
Participants recruited from subspecialty clinics at Nemours Children's Clinic in Jacksonville, Florida between February 2016 and January of 2017
Pre-assignment details
9 assessed for eligibility, 4 excluded (3 did not meet inclusion criteria and 1 surgery date significantly delayed), 5 consented and randomized to treatment sequence in dosing phase (3 started on saline followed by USP Glycerin, 2 started on USP glycerin followed by saline).
Participants by arm
| Arm | Count |
|---|---|
| No Intervention: Pre-operative Baseline Phase Baseline data including frequency and severity of fecal soiling and frequency and severity of abdominal pain were collected for a minimum of 2 weeks prior to surgical construction of the ACE stoma. Baseline stool calprotectin and serum electrolytes were collected in the baseline phase prior to initiation of the preoperative bowel prep. Pre-operative data served as the control. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Dose Response - First Intervention | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Effectiveness - Second Intervention | Lack of Efficacy | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | No Intervention: Pre-operative Baseline Phase |
|---|---|
| Age, Categorical <=18 years | 5 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 66.6 months STANDARD_DEVIATION 29.3309 |
| Ambulatory Ambulatory | 4 participants |
| Ambulatory Wheel Chair User | 1 participants |
| Cause of Neurogenic bowel myelomeningocele | 4 participants |
| Cause of Neurogenic bowel Spinal Cord Trauma - MVA | 1 participants |
| Patulent anus | 5 participants |
| Presence of Fecal Incontinence at Baseline | 5 Participants |
| Race/Ethnicity, Customized African-American | 1 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Caucasian | 2 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 |
Outcome results
Primary
Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen
Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. The purpose of this outcome measure was to document the number of individuals who gained continence on NS and USP glycerin. Descriptive statistics was limited to percentage of total participants who achieved continence on each flushing regimen. Data was calculated on the last data point in the final phase for both the NS and USP glycerin flush.
Time frame: Data collection started following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subjects Continent on NS Antegrade Flush | Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen | 1 Participants |
| Subjects Continent on USP Glycerin | Fecal Soiling - Number of Participants That Gained and Maintained Continence on Each Flushing Regimen | 4 Participants |
Primary
Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin
Fecal soiling was defined as non-toilet elimination, which was tracked and documented by the parent/child as direct event recording and tallied as the number of pairs of underwear/protective undergarments soiled with stool per day. Descriptive statistics included mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05, calculated on the data from the last day of the completed NS and USP Glycerin phases of the study. Power analysis conducted using data from this study with α = 0.5, power of .80, correlation between two means of .598, and effect size of 1.554 estimated a sample size of 11 would be needed to minimize the risk of a Type II error to (20%).
Time frame: Data collection began following consent and procedural training and was collected daily from day 1 for the duration of the study, an average of 135 days.
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Continent on NS Antegrade Flush | Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin | 2 underwear soiled/day | Standard Deviation 1.87 |
| Subjects Continent on USP Glycerin | Fecal Soiling - Quantitative Count Detailing the Number of Episodes of Fecal Incontinence Per Day on NS and USP Glycerin | 0.2 underwear soiled/day | Standard Deviation 0.45 |
Comparison: Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. and calculated on the data from the last day of the completed NS and USP Glycerin phases of the study.~Power analysis conducted using data from this study with α = 0.5, power of .80, correlation between two means of .598, and effect size of 1.554 estimated a sample size of 11 would be needed to minimize the risk of a Type II error to (20%).p-value: 0.069751two-sample pooled variance t-test
Secondary
Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject
Stool calprotectin was used to evaluate the impact of NS and USP Glycerin antegrade flush on colonic health. Calprotectin levels were obtained at baseline and following completion of the NS and USP Glycerin dosing phase of the study. Descriptive data analysis included mean and standard deviation for each flush regimen. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Both descriptive and inferential data analysis was calculated on the difference in calprotectin levels between samples obtained at baseline and samples obtained following the completion of the NS and USP Glycerin flush (value at completion of dosing phase - baseline value). The assumption was the length of each dosing phase was sufficient to achieve a credible active washout period and therefore levels obtained at the end of a phase reflected flushing regimen effects colonic health regardless of flush order.
Time frame: Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples
Population: The data from a total of 5 participants were analyzed for NS and 4 participants for USP Glycerin
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Continent on NS Antegrade Flush | Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject | 133.7 μg/g | Standard Deviation 183.359 |
| Subjects Continent on USP Glycerin | Change in Stool Calprotectin Levels Assessed Through Comparing Levels Obtained Following Completion of NS and USP Glycerin Dosing Phases With the Baseline Value For Each Subject | 108 μg/g | Standard Deviation 113.874 |
Comparison: Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. and calculated on the data from the difference in calprotectin levels between samples obtained at baseline and samples obtained following the completion of the NS and USP Glycerin flush in the dosing phase of the study.p-value: 0.8028two-sample pooled variance t-test
Secondary
Cramping With Flush
Cramping with flush was measured using the Wong Baker Faces Pain Rating Scale (WBFPRS). The WBFPRS has undergone extensive testing and has well established psychometrics in the pediatric population. The scale ranges from 0 (very happy without pain) to 10 (the worse pain imaginable). Each pain level is associated with a facial expression. The child is asked to choose the face that best describes his/her level of discomfort (ordinal data). The parent was instructed to call if the child had flushing regimen-associated discomfort greater than a 4 on the WBFPRS. Documentation of pain severity was completed by the parent and child on a data-collection form at the time of occurrence. Descriptive statistics including mean and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the last data point in the dosing phase.
Time frame: Data analysis was completed on data obtained during the last flush in both the NS and USP Glycerin dosing phase
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Continent on NS Antegrade Flush | Cramping With Flush | 0 units on a scale | Standard Deviation 0 |
| Subjects Continent on USP Glycerin | Cramping With Flush | 0.4 units on a scale | Standard Deviation 0.89 |
Comparison: Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. and calculated on the data from the last day of the completed NS and USP Glycerin phases of the study.p-value: 0.346594two-sample pooled variance t test
Secondary
Flush Volume
Flush volume was measured in mL/flush using a graduated cylinder and recorded by the parent or child with each flush and later calculated in mL/kg. Data derived from the last flush of the completed dosing phase of both NS and USP Glycerin were used to calculate flush volume. Descriptive analysis included mean, median, range, and standard deviation. Reported data excludes subjects who failed to gain and maintain continence on either flushing regimen.
Time frame: Data for analysis was collected from the last flush of the NS and USP Glycerin dosing phase of the study
Population: Subjects limited to those who gained continence (2 saline, 4 USP Glycerin). One subject gained and maintained continence on saline in both the dosing and maintenance phases of the study and one subject who gained continence during the dosing phase of the study but failed to maintain continence on saline during the maintenance phase of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Continent on NS Antegrade Flush | Flush Volume | 39.215 mL/flush | Standard Deviation 12.424 |
| Subjects Continent on USP Glycerin | Flush Volume | 1.475 mL/flush | Standard Deviation 0.457 |
Secondary
NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence
Flush administration frequency necessary to achieve continence was recorded as a single measure per subject per flush solution obtained as the number of flushes in the last three days of each dosing phase and recorded as either daily (1), every other day (2), or every third day (3). The larger the value, the less frequent the flush, the better the clinical outcome. Dosing frequency was measured using direct observational recording completed by the parent or child. Descriptive analysis included mean, and standard deviation. Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. Descriptive and inferential statistics were calculated on the data from the last day of the completed NS and USP Glycerin phases of the study.
Time frame: Frequency of administration data was collected as the total number of flushes recieved over the last three days of each dosing phase for both NS and USP Glycerin and recorded as either daily (1), every other day (2), or every third day
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Continent on NS Antegrade Flush | NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence | 1 Flush administration/day | Standard Deviation 0 |
| Subjects Continent on USP Glycerin | NS and USP Glycerin Flush Solution Dosing Frequency Necessary to Achieve Continence | 1.6 Flush administration/day | Standard Deviation 0.894 |
Comparison: Inferential statistical analysis was accomplished using a two-tailed, two-sample pooled variance t test with a significance level set at 0.05. and calculated on the data from the last day of the completed NS and USP Glycerin phases of the study.p-value: 0.172two-sample pooled variance t-test
Secondary
Number of Participants Experiencing Vagal Symptoms With Flush
Vagal symptoms including nausea, vomiting, sweating, dizziness, and pallor were noted by the parent. The parent was instructed to call if the child had any vagal symptoms. Documentation of any vagal symptoms was completed by the parent and child on a data-collection form at the time of occurrence. Data was analyzed as a percentage of subjects experiencing vagal symptoms during flush with NS and USP glycerin.
Time frame: Data collection started with the first flush administered following discharge from the hospital and was collected with every subsequent flush through completion of the study, an average of 115 days.
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subjects Continent on NS Antegrade Flush | Number of Participants Experiencing Vagal Symptoms With Flush | 0 Participants |
| Subjects Continent on USP Glycerin | Number of Participants Experiencing Vagal Symptoms With Flush | 1 Participants |
Secondary
Number of Participants With Any Electrolyte Abnormality
Evaluated impact of NS and USP Glycerin antegrade flush on serum electrolytes using a blood test called a Basic Metabolic Panel. Data analysis limited to percentage of subjects demonstrating any electrolyte abnormality on NS or USP glycerin.
Time frame: Collection dates included a baseline sample (week 1) and at the completion of the dosing trail for both NS and USP glycerin for a total of 3 samples
Population: The data from a total of 5 participants were analyzed for each arm of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subjects Continent on NS Antegrade Flush | Number of Participants With Any Electrolyte Abnormality | 0 Participants |
| Subjects Continent on USP Glycerin | Number of Participants With Any Electrolyte Abnormality | 0 Participants |