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

Study Overview
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Brief Summary
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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
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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.

Official Title
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iKanEat: A Randomized-controlled, Multi-center Trial of Megestrol for Chronic Oral Food Refusal in Children 9 Months to 9 Years 0 Months of Age

Conditions
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Feeding Behavior, Feeding Disorder of Infancy or Early Childhood

Intervention / Treatment
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* Drug: Megestrol Acetate
* Behavioral: iKanEat Behavioral Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 9 months to 9y0m at the time of consent. Able to obtain parental or legal guardian written informed consent from subjects as applicable by local laws and regulations. Subjects must have a G or G/J tube. Subjects must receive over 80% of their total daily calorie needs from a tube in order to be classified as tube dependent. 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. Subjects must possess the oral motor skills necessary for eating. Subjects must possess behavioral skills necessary for mealtimes. Exclusion Criteria: Children receiving oral or inhaled steroids. 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). 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). Children of non-English speaking parents.

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 108 Months

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
Interventional Model Description: 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).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Megestrol<br>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. | Drug: Megestrol Acetate<br>* 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.<br>* Other names: Megestrol;Behavioral: iKanEat Behavioral Intervention<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Behavioral: iKanEat Behavioral Intervention<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in % kilocalories/day obtained orally | What percentage of kilocalories come from oral feedings as opposed to g-tube feeding. | Weeks 0 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adrenal insufficiency as measured by morning cortisol lab value | The investigators will determine whether any of our participants in either group have adrenal sufficiency levels outside of the normal range at any time point. Should any participant have levels outside of the normal range, the investigators will descriptively examine the individual characteristics associated with this, including group assignment, medical diagnoses, sex, and age at initiation. These characteristics will be reported descriptively. | 10 to 14 weeks | 
| Change in parent stress as measured by the Pediatric Inventory for Parents (PIP36) | The investigators will model parent stress levels from Week 0 to Week 24 of the intervention. The PIP is scored separately for each of the 4 domains (Communication, Emotional Distress, Medical Care, Role Function), across 2 scales: Frequency (F) and Difficulty (D). There is also a total score comprised of the sum for each of the 4 domains, yielding Total F and Total D scores. Items are scored as endorsed by respondents, ranging from 1-5. The range for each of the Total F and Total D scores is 42-210. Higher scores are indicative of worse parent stress outcomes. | Weeks 0 to 24 | 
| Change in child quality of life as measured by the Infant Toddler Quality of Life scale (ITQOL47) | The investigators will model child quality of life from Week 0 to Week 24 of the intervention. The Infant Toddler Quality of Life Questionnaire™ (ITQOL) was developed for use in infants and toddlers from 2-months-to-5 years of age. The Infant Toddler Quality of Life Questionnaire™ (ITQOL) adopts the World Health Organization's definition of health, as a state of complete physical, mental and social wellbeing and not merely the absence of disease. For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). | Week 0 to 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrostomy Tube, G-Tube, Oral Food Refusal, Behavioral Intervention, Megestrol, Transition to Oral Feedings, Weaning