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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
70
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.
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.
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
Participants Who Transitioned to Oral Feeding
The efficacy of megestrol as part of the 24 week iKanEat protocol will be measured by participants who successfully transitioned to oral feeding, defined at at least 90% calories consumed orally.
Time frame: Weeks 0 to 24
Number of Participants 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.
Time frame: 10 to 14 weeks
Change in Child Quality of Life as Measured by the Infant Toddler Quality of Life Scale (ITQOL47) - Global Behavior (GB2) Subscale
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).
Time frame: Week 0 to 24
Change in Child Quality of Life as Measured by the Infant Toddler Quality of Life Scale (ITQOL47) - Combined Behavior Scale (CBE) Subscale
he 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).
Time frame: Week 0 to 24
Change in Child Quality of Life as Measured by the Child Health Questionnaire Parent Form - CHQ-PF50, 5.1 Behavior (BE) Subscale
Child quality of life in children aged ≥5 years will be assessed using the Child Health Questionnaire Parent Form - CHQ-PF50, a validated parent-reported measure of physical and psychosocial health for children ages 5-18. The CHQ-PF50 contains 50 items assessing 14 health concepts, including physical functioning, emotional/behavioral well-being, social functioning, and family impact. The Behavior (BE) subscale evaluates behavioral and emotional adjustment as observed by the parent. Subscale scores range from 0 to 100, with higher scores representing better behavioral health and fewer behavioral problems. CHQ-PF50 scores can be analyzed at the subscale level (CHQ Profile Scores) or combined into Summary Scores for physical and psychosocial health. Summary scores are calculated by averaging standardized subscale scores, also ranging from 0 to 100, with higher scores indicating better overall health-related quality of life.
Time frame: Week 0 to 24
Change in Child Quality of Life as Measured by the Child Health Questionnaire Parent Form - CHQ-PF50 - 5.2 Global Behavior (GBE) Subscale
Child quality of life in children aged ≥5 years will be assessed using the Child Health Questionnaire Parent Form - CHQ-PF50, a validated parent-reported measure of physical and psychosocial health for children ages 5-18. The CHQ-PF50 includes 50 items covering 14 health concepts, such as physical functioning, emotional/behavioral well-being, social functioning, and family impact. The Global Behavior (GBE) subscale assesses overall behavioral and emotional functioning as reported by the parent. Subscale scores range from 0 to 100, with higher scores indicating better global behavioral health and fewer overall behavioral problems. CHQ-PF50 scores can be analyzed at the subscale level (CHQ Profile Scores) or combined into Summary Scores for physical and psychosocial health. Summary scores are calculated by averaging standardized subscale scores, also ranging from 0 to 100, with higher scores representing better overall health-related quality of life.
Time frame: Week 0 to 24
Change in Parent Stress as Measured by the Pediatric Inventory for Parents (PIP36) - Total Frequency Score
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.
Time frame: Weeks 0 to 24
Change in Parent Stress as Measured by the Pediatric Inventory for Parents (PIP36) - Total Difficulty Score
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.
Time frame: Weeks 0 to 24
Change in Parent Quality of Life as Measured by the SF-36v2 - Emotional Well-Being Subscale
Parent quality of life will be assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36v2), a widely used, validated self-report measure of general health-related quality of life. The SF-36v2 includes 36 items covering 8 domains: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. The Emotional Well-Being (Mental Health) subscale measures overall emotional functioning, including mood, anxiety, and psychological distress. Raw subscale scores range from 0 to 100, with higher scores indicating better emotional well-being. For analysis, raw subscale scores will be converted to standardized Z-scores, where a Z-score of 0 represents the population mean, and each standard deviation above or below 0 represents deviation from the mean. Higher Z-scores indicate better emotional functioning, while lower Z-scores indicate worse emotional
Time frame: Week 0 to 24
Change in Parent Depressive Symptoms Measured by the Patient Health Questionnaire-9 (PHQ-9)
Parent depressive symptoms will be assessed using the Patient Health Questionnaire-9 (PHQ-9), a validated 9-item self-report measure of depression severity based on the 9 criteria for Major Depressive Disorder (MDD) from the DSM. Each item is scored from 0 ("not at all") to 3 ("nearly every day"), yielding a total score ranging from 0 to 27. Higher PHQ-9 scores indicate greater severity of depressive symptoms, while lower scores indicate fewer or less severe depressive symptoms. Total score interpretation is commonly as follows: 0-4 = minimal or no depression, 5-9 = mild depression, 10-14 = moderate depression, 15-19 = moderately severe depression, 20-27 = severe depression. This measure can be used to assess both the presence of depressive symptoms and changes in symptom severity over time.
Time frame: Week 0 to 24
Change in Parent Anxiety Symptoms Measured by the General Anxiety Disorder-7 (GAD-7).
Parent anxiety symptoms will be assessed using the Generalized Anxiety Disorder-7 (GAD-7), a validated 7-item self-report measure that screens for and assesses the severity of common anxiety disorders, including Generalized Anxiety Disorder, Panic Disorder, Social Phobia, and Post-Traumatic Stress Disorder. Each item is scored from 0 ("not at all") to 3 ("nearly every day"), yielding a total score range of 0 to 21. Higher scores indicate greater anxiety symptom severity, whereas lower scores indicate fewer or less severe anxiety symptoms. Total scores are interpreted as follows: 0-4 = minimal anxiety, 5-9 = mild anxiety, 10-14 = moderate anxiety, 15-21 = severe anxiety. The total GAD-7 score is calculated by summing the scores for all seven items. This measure can be used to assess the presence of clinically significant anxiety symptoms as well as changes in symptom severity over time.
Time frame: Week 0 to 24
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