Gastrointestinal Dysmotility on Aspiration Risk

Study Overview
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Brief Summary
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The hypothesis of this study is that esophageal and gastric dysmotility increase the risk of developing aspiration-associated symptoms in children with neurologic impairment. The investigators are conducting a ten week cross over study comparing prucalopride to famotidine for the treatment of aspiration-associated symptoms.

Official Title
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The Impact of Upper Gastrointestinal Dysmotility on Aspiration-associated Symptoms

Conditions
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Esophageal Motility Disorders, Gastric Motor Dysfunction, Aspiration Pneumonia, Gastro Esophageal Reflux

Intervention / Treatment
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* Drug: Prucalopride
* Drug: Famotidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are 5-21 years of age; receive >90% of their calories by enteral tube (i.e., patients take no food or drink by mouth); are determined to be at high risk for aspiration pneumonia based on evidence of impaired airway protective mechanisms, documented by aspiration on video fluoroscopic swallow study; have static neurologic impairment, defined as functional and/or intellectual impairment that results from a chronic neurologic or related diagnosis (e.g., cerebral palsy) with no prospect of progression for at least one year; have chronic respiratory symptoms, defined as coughing, choking, or need for oral suctioning a minimum of three times per week during the prior four weeks. - Exclusion Criteria: have progressive neurologic impairment; have a history of prior intact Nissen fundoplication; are currently taking oral or inhaled antibiotics, including prophylactic antibiotics; are currently taking or have taken in the last four weeks acid suppression (H2 antagonist or PPI); or are fed by gastrojejunostomy rather than by gastrostomy. -

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Patients will be undergo 1 week observation period followed by 4 weeks of prucalopride followed by 1 weeks of a wash out followed by 4 weeks of famotidine | Drug: Prucalopride<br>* Prucalopride 0.04 mg/kg/day<br>Drug: Famotidine<br>* Famotidine 0.4 mg/kg/day<br>|
| Experimental: Arm 2<br>Patients will be undergo 1 week observation period followed by 4 weeks of famotidine followed by 1 weeks of a wash out followed by 4 weeks of prucalopride | Drug: Prucalopride<br>* Prucalopride 0.04 mg/kg/day<br>Drug: Famotidine<br>* Famotidine 0.4 mg/kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pediatric Cough Quality of Life Questionnaire | Comparison of the mean difference in the Pediatric Cough Quality of Life Questionnaire (range: 7 to 189, lower scores=more symptom impairment) between baseline and 4 week scores between Arm 1 and Arm 2 | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying outcomes | Comparison of within-patient differences in gastric residuals by nuclear scintigraphy | 4 weeks | 
| Total Peds-GI QL score | Comparison of the mean difference in total Peds-GI QL scores (range: 0-100, lower=worse symptoms) between famotidine and prucalopride periods | 8 weeks | 
| Aspiration symptoms | Comparison of the mean difference in the number of coughing or choking episodes per week during the fourth week of treatment | 4 weeks | 
| Microbiome | Comparison of within-patient differences in microbiome diversity and abundance between baseline and after each medication period | 8 weeks | 
| Pneumonias | Comparisons in the number of aspiration pneumonias between each treatment period | 10 weeks | 
| Esophageal reflux events | Comparison of within-patient differences in post-prandial reflux events by nuclear scintigraphy | 4 weeks |