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

This study has been completed.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Ann Davis, PhD, MPH, ABPP, University of Kansas Medical Center Research Institute
ClinicalTrials.gov Identifier:
NCT01206478
First received: September 20, 2010
Last updated: July 1, 2016
Last verified: May 2016

September 20, 2010
July 1, 2016
August 2010
December 2014   (final data collection date for primary outcome measure)
% Calories Taken Orally [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
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.
To assess the efficacy of amitriptyline in a 24-week outpatient multi-disciplinary protocol for transitioning children from tube to oral feeding [ Time Frame: weekly for 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01206478 on ClinicalTrials.gov Archive Site
Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
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.
To assess the role of pain in the efficacy of amitriptyline in the 24-week outpatient multidisciplinary protocol. [ Time Frame: weekly for 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age
A Phase II, Randomized-Controlled, Multicenter Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Chronic Oral Food Refusal
  • Drug: Amitriptyline
    Amitriptyline 1 mg/kg once daily at bedtime.
  • Drug: Placebo
    Placebo (looks like study drug but has no active ingredients) once daily at bedtime.
  • Drug: Megestrol
    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.
  • Experimental: Amitriptyline plus Megestrol
    Amitriptyline once daily at bedtime plus megestrol starting at visit 2
    Interventions:
    • Drug: Amitriptyline
    • Drug: Megestrol
  • Active Comparator: Placebo plus Megestrol
    Matching placebo once daily at bedtime plus megestrol starting at visit 2
    Interventions:
    • Drug: Placebo
    • Drug: Megestrol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
December 2014
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria

Subjects must meet all of the following inclusion criteria:

  1. Males or females 9 months to 8 years 0 months 0 days of age.
  2. Able to obtain parental or legal guardian written informed consent from subjects as applicable by local laws and regulations.
  3. Subjects must possess the oral motor skills necessary for eating according to Table 1 in the Appendix.
  4. Subjects must possess behavioral skills necessary for mealtime according to Table 2 in the Appendix.
  5. 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.
  6. 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:

  1. Children on MAO inhibitors or who have thyroid problems will be excluded.
  2. Children with diabetes or adrenal insufficiency will be excluded.
  3. Children with known heart conduction abnormalities.
  4. Children taking tricyclic medications.
Both
9 Months to 8 Years   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01206478
12261, R21HD066629
Yes
No
Not Provided
Ann Davis, PhD, MPH, ABPP, University of Kansas Medical Center Research Institute
Ann Davis, PhD, MPH, ABPP
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Ann Davis, Ph.D., MPH, ABPP University of Kansas Medical Center
University of Kansas Medical Center
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP