Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age

Study Overview
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Brief Summary
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Gastrojejunal (G-J) feeding tubes are placed in infants and children who refuse to eat or are unable to eat enough to have normal growth. Although often intended as temporary short-term solutions to medical complications, feeding tubes can become a permanent method for eating. While tube feeding routinely saves the lives of children who have long term food refusal, continuation of tube feeding can be hard for patients, caregivers, and families. At the current time there are few treatments for helping children move from tube to oral feeding. Some patients may be treated with the help of inpatient programs such as a combination of medical and behavioral techniques to train children to eat orally. These programs typically require hospital stays of 2-4 months. By doing the current study the investigators hope to learn if the investigational drug amitriptyline is helpful in moving children from tube to oral feeding, and to look at whether or not the treatment of pain helps with this transition.

Detailed Description
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This research study involves a study drugs called amitriptyline and megestrol. Amitriptyline might help children who have feeding problems with pain and megestrol is known to increase appetite. Amitriptyline and megestrol are liquid syrups that are given by feeding tube daily. Amitriptyline has not been approved by the United States Food and Drug Administration (FDA) for the treatment of child with feeding problems. Amitriptyline is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for child with feeding problems. Amitriptyline is approved by the FDA for the treatment of depression. Megestrol has not been approved by the United States Food and Drug Administration (FDA) for the treatment of children with feeding problems. Megestrol is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for children with feeding problems. Megestrol has been approved by the FDA for the treatment of adults. Though megestrol is not FDA approved to treat children with feeding problems, it is often used for this purpose. Megestrol and Amitriptyline both affect the nerve cells that carry pain sensations to and from the brain. Both drugs reduce the intensity of the pain signals going to the part of the brain that feels pain. Each drug attaches to the nerve cell but at separate spots on the nerve cell so pain can be better managed.

Official Title
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A Phase II, Randomized-Controlled, Multicenter Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age

Conditions
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Chronic Oral Food Refusal

Intervention / Treatment
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* Drug: Amitriptyline
* Drug: Placebo
* Drug: Megestrol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects must meet all of the following inclusion criteria: Males or females 9 months to 8 years 0 months 0 days of age. Able to obtain parental or legal guardian written informed consent from subjects as applicable by local laws and regulations. Subjects must possess the oral motor skills necessary for eating according to Table 1 in the Appendix. Subjects must possess behavioral skills necessary for mealtime according to Table 2 in the Appendix. Subjects must have a history of chronic oral food refusal (3 months of refusing to eat more than 5% of their caloric intake orally) and be fed >95% of their caloric intake through a gastrostomy tube for 3 months or longer. Subjects will be required to have a body mass index for age/gender of 25% or greater prior to beginning the protocol to ensure that subjects are sufficiently nourished. Exclusion Criteria Study enrollment will exclude potential subjects with any of the following conditions or taking any of the following medication: Children on MAO inhibitors or who have thyroid problems will be excluded. Children with diabetes or adrenal insufficiency will be excluded. Children with known heart conduction abnormalities. Children taking tricyclic medications.

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amitriptyline plus Megestrol<br>Amitriptyline once daily at bedtime plus megestrol starting at visit 2 | Drug: Amitriptyline<br>* Amitriptyline 1 mg/kg once daily at bedtime.<br>Drug: Megestrol<br>* At Visit 2, after participating in the study for ten weeks, children will receive a prescription for the appetite stimulant megestrol. The dose each child will receive depends on their age and weight. The dose of megestrol is 6 mg/kg divided into two doses per day.<br>|
| Active Comparator: Placebo plus Megestrol<br>Matching placebo once daily at bedtime plus megestrol starting at visit 2 | Drug: Placebo<br>* Placebo (looks like study drug but has no active ingredients) once daily at bedtime.<br>Drug: Megestrol<br>* At Visit 2, after participating in the study for ten weeks, children will receive a prescription for the appetite stimulant megestrol. The dose each child will receive depends on their age and weight. The dose of megestrol is 6 mg/kg divided into two doses per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % Calories Taken Orally | Percent Kilocalories (kcal) Obtained Orally. This measure was obtained using the 24 hour food recall, a standardized five-pass method developed by the US Department of Agriculture for use in national dietary surveillance. This measure has been widely used in several large trials and data suggest it is the most valid and reliable method of dietary assessment for children (20). The data were collected at week 0, week 10, and week 24 using standardized probes by highly trained research staff, and parents were presented with paper food models and measuring devices prior to interviews to reference during the recall. Recalls were analyzed with the Nutritional Data System for Research, version 2005; University of Minnesota, Minneapolis, MN. | baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores | Non-communicating Children's Pain Checklist - Revised (NCCPC-R) used to measure outcome. The NCCPC-R is a 30 item measure intended to assess pain in children who are unable to speak because of cognitive or physical impairments. There are 7 sub-scales including vocal, social, facial, activity, body/limbs, physiological, and eating/sleeping. Each question has a potential score of 0 to 3. Scores are totaled for each sub-scale. Sub-scale scores are then added together for the Total Score. Total Scores can range from 0 to 90. The higher the score, the higher level of pain indicated by the child. This measure was completed by parents at week 0, week 10, and week 24. | baseline, 24 weeks |