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

NCT01206478 | Completed Phase 2 Results DMC

• 2 other identifiers: 12261R21HD066629
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Chronic Oral Food Refusal

Outcome Measures

Primary Outcomes (1)

• % 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 Outcomes (1)

• Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores

  baseline, 24 weeks

Study Arms (2)

Amitriptyline plus Megestrol

EXPERIMENTAL

Amitriptyline once daily at bedtime plus megestrol starting at visit 2

Drug: Amitriptyline; Drug: Megestrol

Placebo plus Megestrol

ACTIVE COMPARATOR

Matching placebo once daily at bedtime plus megestrol starting at visit 2

Drug: Placebo; Drug: Megestrol

Interventions

Amitriptyline DRUG

Amitriptyline 1 mg/kg once daily at bedtime.

Amitriptyline plus Megestrol

Placebo DRUG

Placebo (looks like study drug but has no active ingredients) once daily at bedtime.

Placebo plus Megestrol

Megestrol DRUG

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.

Amitriptyline plus Megestrol; Placebo plus Megestrol

Eligibility Criteria

• Age: 9 Months - 8 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ann Davis, PhD, MPH, ABPP: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Children's Hospital of New Orleans

New Orleans, Louisiana, 70118, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (2)

• Garcia AM, Beauchamp MT, Patton SR, Edwards S, Dreyer Gillette ML, Davis AM. Family mealtime behaviors in children who are tube fed and preparing to transition to oral eating: A comparison to other pediatric populations. J Health Psychol. 2022 Mar;27(4):1014-1020. doi: 10.1177/1359105320982034. Epub 2020 Dec 18.

  PMID: 33339464 DERIVED

• Davis AM, Dean K, Mousa H, Edwards S, Cocjin J, Almadhoun O, He J, Bruce A, Hyman PE. A Randomized Controlled Trial of an Outpatient Protocol for Transitioning Children from Tube to Oral Feeding: No Need for Amitriptyline. J Pediatr. 2016 May;172:136-141.e2. doi: 10.1016/j.jpeds.2016.02.013. Epub 2016 Mar 3.

  PMID: 26947568 DERIVED

MeSH Terms

Interventions

Amitriptyline; Megestrol

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Major weakness was our small sample size, which was directly due to problems with recruitment, which occurred uniformly across sites. The primary reason for refusal was that parents did not want to be randomly assigned to the amitriptyline/placebo.

Results Point of Contact

• Title: Ann M Davis, PI
• Organization: University of Kansas Medical Center

adavis6@kumc.edu

913-588-6300

Study Officials

• Ann Davis, Ph.D., MPH, ABPP

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 20, 2010
• First Posted: September 21, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 15, 2016
• Results First Posted: August 15, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)