iKanEat: A Randomized-controlled, Multi-center Trial of Megestrol for Chronic Oral Food Refusal in Children

NCT ID: NCT03815019

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-15
• Study Completion Date: 2025-03-19

Brief Summary

This is a multi-center, randomized, placebo-controlled, double-blind clinical trial. The primary focus of the study is the evaluation of the effectiveness of treatment with megestrol as part of a 24 week behavioral feeding protocol in transitioning from tube to oral feedings in a pediatric population. Approximately 60 pediatric subjects matching the criteria for eligibility will be enrolled in the study and randomized to receive either megestrol (n=30) or placebo (n=30).

Detailed Description

The primary aim of the current study is to conduct a randomized controlled trial of a 4-week course of megestrol, the only remaining medication that is part of the iKanEat protocol, to ensure that the addition of megestrol results in improved child outcomes. The second aim is to assess the safety of megestrol as part of the iKanEat protocol. Our previous work (as well as work by others) suggests that a 6 week course of megestrol can lead to adrenal insufficiency in some children, so as part of the current protocol, the investigators will assess the safety of a 4 week course of this drug.

Finally, parents of tube fed children encounter multiple psychosocial stressors regarding tube feeding. These include concerns about their child's survival due to their underlying medical issues, feelings of "failure" due to their inability to feed their child orally, increased feelings of stress around the tube feeding and decreased support from others due to the tube feeding. Our research indicates that quality of life can be poor in tube fed children, even more so than children with cancer or burns. Given the significance of these issues, the third aim of the study is to examine the effect of the transition from tube to oral feeding on parent stress and parent and child quality of life.

Aim 1: To assess the efficacy of megestrol as part of the 24 week iKanEat protocol.

Hypothesis 1: Children randomized to the megestrol group will be significantly more successful in making the transition to oral feeding (defined as obtaining at least 90% of calories orally) than children randomized to the placebo group.

Aim 2: To assess the safety of 4 weeks of megestrol as part of the 24 week iKanEat protocol.

Hypothesis 2A: Children randomized to the megestrol group will not differ from control children in morning cortisol classification level (low, average, high) and will remain within the normal range at all time points. Analyses 2B: Exploratory analysis will determine which, if any, covariates (gender, age, and diagnoses at week 0, diagnoses at birth) are related to abnormal morning cortisol levels.

Aim 3: To examine the effect of the transition from tube to oral feeding on parent stress and parent and child quality of life. Hypothesis 3A: The transition to oral feeding will temporarily increase parent stress at week 14 at the cessation of tube feeding, with a return to baseline by week 24. Hypothesis 3B: The transition to oral feeding will increase parent/child quality of life at 24 weeks compared to week 0. Children with feeding tubes have few options for treatment other than extensive inpatient stays and expensive day treatment programs. iKanEat offers an outpatient, less intensive, empirically supported effective treatment option that can improve the lives of children and families. It is imperative that the investigators determine the efficacy and safety of the protocol including 4 weeks of megestrol before the investigators move toward broad dissemination of the iKanEat protocol.

Conditions

Feeding Behavior; Feeding Disorder of Infancy or Early Childhood

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Megestrol

Megestrol is a steroid and progestational drug FDA approved for treating anorexia or weight loss in patients with acquired immunodeficiency syndrome. Its use in the current protocol is "off label" to stimulate appetite in tube-fed infants and toddlers who are weaning from tube feedings and learning to eat. The precise mechanism of action that leads to increased appetite and weight gain is unknown, but is probably related to megestrol's glucocorticoid effect.

The proposed study will use megestrol 6 mg/kg/day in two doses because this dose has been effective and safe in two previous studies using megestrol to stimulate appetite in children transitioning from tube to oral feedings. The megestrol will be dosed at full dose weeks 10-11, at 66% dose week 12, at 33% dose week 14, and fully tapered at the end of week 14. Megestrol is absorbed from the small bowel, so feeding it through the tube will be acceptable.

Group Type: EXPERIMENTAL

Megestrol Acetate

Intervention Type: DRUG

The proposed study will use megestrol 6 mg/kg/day in two doses because this dose has been effective and safe in two previous studies using megestrol to stimulate appetite in children transitioning from tube to oral feedings. The megestrol will be dosed at full dose weeks 10-11, at 66% dose week 12, at 33% dose week 14, and fully tapered at the end of week 14. Megestrol is absorbed from the small bowel, so feeding it through the tube will be acceptable.

iKanEat Behavioral Intervention

Intervention Type: BEHAVIORAL

The 24 week iKanEat intervention is composed of 4 clinic visits and a series of 12 tele-visits. All visits (clinic and tele-visits) will focus directly on the oral-motor and behavioral skills necessary for oral eating.

Tele-visits will begin by building rapport and asking for a summary of all relevant information since the last point of contact, including parent perception of changes in weight, feeding habits, progress, stress of parent/child, and illness. The majority of the time left in the 30 minute session will be spent dealing with parent concerns, which our previous project indicates may include questions about measures, questions about implementation of the iKanEat protocol, and ensuring that children/families adhere to the oral-motor and behavioral guidelines for feeding.

Placebo

Subjects randomized to the placebo protocol will receive a placebo syrup identical in taste and smell to megestrol at the same intervals as those in the megestrol group but the syrup will contain no active ingredients.

Group Type: PLACEBO_COMPARATOR

iKanEat Behavioral Intervention

Intervention Type: BEHAVIORAL

The 24 week iKanEat intervention is composed of 4 clinic visits and a series of 12 tele-visits. All visits (clinic and tele-visits) will focus directly on the oral-motor and behavioral skills necessary for oral eating.

Tele-visits will begin by building rapport and asking for a summary of all relevant information since the last point of contact, including parent perception of changes in weight, feeding habits, progress, stress of parent/child, and illness. The majority of the time left in the 30 minute session will be spent dealing with parent concerns, which our previous project indicates may include questions about measures, questions about implementation of the iKanEat protocol, and ensuring that children/families adhere to the oral-motor and behavioral guidelines for feeding.

Interventions

Megestrol Acetate

The proposed study will use megestrol 6 mg/kg/day in two doses because this dose has been effective and safe in two previous studies using megestrol to stimulate appetite in children transitioning from tube to oral feedings. The megestrol will be dosed at full dose weeks 10-11, at 66% dose week 12, at 33% dose week 14, and fully tapered at the end of week 14. Megestrol is absorbed from the small bowel, so feeding it through the tube will be acceptable.

Intervention Type: DRUG

iKanEat Behavioral Intervention

The 24 week iKanEat intervention is composed of 4 clinic visits and a series of 12 tele-visits. All visits (clinic and tele-visits) will focus directly on the oral-motor and behavioral skills necessary for oral eating.

Tele-visits will begin by building rapport and asking for a summary of all relevant information since the last point of contact, including parent perception of changes in weight, feeding habits, progress, stress of parent/child, and illness. The majority of the time left in the 30 minute session will be spent dealing with parent concerns, which our previous project indicates may include questions about measures, questions about implementation of the iKanEat protocol, and ensuring that children/families adhere to the oral-motor and behavioral guidelines for feeding.

Intervention Type: BEHAVIORAL

Other Intervention Names

Megace; Megestrol

Eligibility Criteria

Inclusion Criteria

1. Males and females aged 9 months to 9y0m at the time of consent.

2. Able to obtain parental or legal guardian written informed consent from subjects as applicable by local laws and regulations.

3. Subjects must have a G or G/J tube.

4. Subjects must receive over 80% of their total daily calorie needs from a tube in order to be classified as tube dependent.

5. Subjects must have a ≥ 3 month history of feeding problems as identified by a diagnosis from a multidisciplinary feeding team, and must have permission from the physician on the team to ensure that they are medically stable enough to participate in a weaning study.

6. Subjects must possess the oral motor skills necessary for eating. Subjects must possess behavioral skills necessary for mealtimes.

Exclusion Criteria

1. Children receiving oral or inhaled steroids.

2. Parent has a known developmental delay or cognitive impairment that may make participation in the study difficult (children with these issues will not be excluded).

3. Children receiving intensive (defined as more than one session per month) behavioral feeding therapy with a licensed psychologist (previous behavioral feeding therapy is not an exclusion criterion; neither is current oral-motor, sensory, or speech therapy).

4. Children of non-English speaking parents.

• Minimum Eligible Age: 9 Months
• Maximum Eligible Age: 108 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ann Davis, PhD, MPH, ABPP

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rady Children's Hospital - San Diego

San Diego, California, United States

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Riley Hospital for Children at IU Health

Indianapolis, Indiana, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Countries

United States

References

Edwards S, Hyman PE, Mousa H, Bruce A, Cocjin J, Dean K, Fleming K, Romine RS, Davis AM. iKanEat: protocol for a randomized controlled trial of megestrol as a component of a pediatric tube weaning protocol. Trials. 2021 Feb 27;22(1):169. doi: 10.1186/s13063-021-05131-w.

Reference Type: BACKGROUND

PMID: 33640012 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STUDY00142352

Identifier Type: -

Identifier Source: org_study_id