Trial Outcomes & Findings for iKanEat: A Randomized-controlled, Multi-center Trial of Megestrol for Chronic Oral Food Refusal in Children (NCT NCT03815019)

NCT ID: NCT03815019

Last Updated: 2025-09-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 70 participants
• Primary outcome timeframe: Weeks 0 to 24
• Results posted on: 2025-09-10

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	36	34
Overall Study COMPLETED	30	26
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Measure	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.	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.
Overall Study Withdrawal by Subject	6	8

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Megestrol n=36 Participants 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.	Placebo n=34 Participants 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.	Total n=70 Participants Total of all reporting groups
Age, Continuous	4.06 years STANDARD_DEVIATION 2.08 • n=5 Participants	4.20 years STANDARD_DEVIATION 2.54 • n=7 Participants	4.15 years STANDARD_DEVIATION 2.30 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	20 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	14 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants	30 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
% calories from oral intake	18.51 % calories from oral intake STANDARD_DEVIATION 16.39 • n=5 Participants	20.50 % calories from oral intake STANDARD_DEVIATION 15.43 • n=7 Participants	19.48 % calories from oral intake STANDARD_DEVIATION 15.85 • n=5 Participants

PRIMARY outcome

Timeframe: Weeks 0 to 24

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.

Outcome measures

Measure	Megestrol n=30 Participants 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.	Placebo n=26 Participants 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.
Participants Who Transitioned to Oral Feeding	23 Participants	24 Participants

SECONDARY outcome

Timeframe: 10 to 14 weeks

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.

Outcome measures

Measure	Megestrol n=31 Participants 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.	Placebo n=26 Participants 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.
Number of Participants With Adrenal Insufficiency as Measured by Morning Cortisol Lab Value	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 0 to 24

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).

Outcome measures

Measure	Megestrol n=19 Participants 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.	Placebo n=17 Participants 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.
Change in Child Quality of Life as Measured by the Infant Toddler Quality of Life Scale (ITQOL47) - Global Behavior (GB2) Subscale	3.4211 scores on a scale Standard Error 4.8652	1.4706 scores on a scale Standard Error 5.1434

SECONDARY outcome

Timeframe: Week 0 to 24

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).

Outcome measures

Measure	Megestrol n=19 Participants 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.	Placebo n=17 Participants 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.
Change in Child Quality of Life as Measured by the Infant Toddler Quality of Life Scale (ITQOL47) - Combined Behavior Scale (CBE) Subscale	0.3947 scores on scale Standard Error 2.4536	-0.9804 scores on scale Standard Error 2.5939

SECONDARY outcome

Timeframe: Week 0 to 24

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.

Outcome measures

Measure	Megestrol n=10 Participants 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.	Placebo n=7 Participants 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.
Change in Child Quality of Life as Measured by the Child Health Questionnaire Parent Form - CHQ-PF50, 5.1 Behavior (BE) Subscale	5.0000 scores on a scale Standard Error 5.0249	8.3333 scores on a scale Standard Error 6.0059

SECONDARY outcome

Timeframe: Week 0 to 24

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.

Outcome measures

Measure	Megestrol n=10 Participants 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.	Placebo n=7 Participants 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.
Change in Child Quality of Life as Measured by the Child Health Questionnaire Parent Form - CHQ-PF50 - 5.2 Global Behavior (GBE) Subscale	-2.5000 scores on a scale Standard Error 5.2678	-0.000000000001 scores on a scale Standard Error 6.2963

SECONDARY outcome

Timeframe: Weeks 0 to 24

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.

Outcome measures

Measure	Megestrol n=28 Participants 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.	Placebo n=24 Participants 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.
Change in Parent Stress as Measured by the Pediatric Inventory for Parents (PIP36) - Total Frequency Score	-20.7500 scores on a scale Standard Error 5.2481	-21.2500 scores on a scale Standard Error 5.6686

SECONDARY outcome

Timeframe: Weeks 0 to 24

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.

Outcome measures

Measure	Megestrol n=28 Participants 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.	Placebo n=24 Participants 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.
Change in Parent Stress as Measured by the Pediatric Inventory for Parents (PIP36) - Total Difficulty Score	-18.7143 scores on a scale Standard Error 5.6856	-21.2083 scores on a scale Standard Error 6.1411

SECONDARY outcome

Timeframe: Week 0 to 24

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

Outcome measures

Measure	Megestrol n=29 Participants 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.	Placebo n=24 Participants 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.
Change in Parent Quality of Life as Measured by the SF-36v2 - Emotional Well-Being Subscale	0.9655 z-score Standard Error 2.5131	3.0000 z-score Standard Error 2.7625

SECONDARY outcome

Timeframe: Week 0 to 24

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.

Outcome measures

Measure	Megestrol n=28 Participants 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.	Placebo n=23 Participants 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.
Change in Parent Depressive Symptoms Measured by the Patient Health Questionnaire-9 (PHQ-9)	-0.5357 scores on a scale Standard Error 0.9456	0.4783 scores on a scale Standard Error 0.4783

SECONDARY outcome

Timeframe: Week 0 to 24

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.

Outcome measures

Measure	Megestrol n=28 Participants 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.	Placebo n=23 Participants 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.
Change in Parent Anxiety Symptoms Measured by the General Anxiety Disorder-7 (GAD-7).	-0.9643 scores on a scale Standard Error 0.7912	-0.7826 scores on a scale Standard Error 0.8730

Adverse Events

Megestrol

Serious events: 5 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Megestrol n=36 participants at risk 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.	Placebo n=34 participants at risk 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.
Gastrointestinal disorders Post-surgical ileus	2.8% 1/36 • Number of events 1 • 24 Weeks	0.00% 0/34 • 24 Weeks
Cardiac disorders Tachycardia	2.8% 1/36 • Number of events 1 • 24 Weeks	0.00% 0/34 • 24 Weeks
Renal and urinary disorders Urinary Tract Infection	2.8% 1/36 • Number of events 1 • 24 Weeks	0.00% 0/34 • 24 Weeks
Immune system disorders Allergenic reaction to food	2.8% 1/36 • Number of events 1 • 24 Weeks	0.00% 0/34 • 24 Weeks
Metabolism and nutrition disorders Weight loss	0.00% 0/36 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks
General disorders Weakness	0.00% 0/36 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks
General disorders Dehydration	2.8% 1/36 • Number of events 1 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks
Injury, poisoning and procedural complications Concussion	0.00% 0/36 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks
Infections and infestations Fever	0.00% 0/36 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks

Other adverse events

Measure	Megestrol n=36 participants at risk 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.	Placebo n=34 participants at risk 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.
Gastrointestinal disorders Constipation	8.3% 3/36 • Number of events 3 • 24 Weeks	2.9% 1/34 • Number of events 1 • 24 Weeks
Gastrointestinal disorders Diarrhea	2.8% 1/36 • Number of events 1 • 24 Weeks	5.9% 2/34 • Number of events 3 • 24 Weeks
Infections and infestations Ear infection	8.3% 3/36 • Number of events 5 • 24 Weeks	11.8% 4/34 • Number of events 4 • 24 Weeks
General disorders Fever	22.2% 8/36 • Number of events 10 • 24 Weeks	14.7% 5/34 • Number of events 6 • 24 Weeks
Psychiatric disorders Irritability	5.6% 2/36 • Number of events 2 • 24 Weeks	0.00% 0/34 • 24 Weeks
Respiratory, thoracic and mediastinal disorders Respiratory virus	27.8% 10/36 • Number of events 15 • 24 Weeks	47.1% 16/34 • Number of events 24 • 24 Weeks
Infections and infestations Streptococcal pharyngitis	5.6% 2/36 • Number of events 2 • 24 Weeks	0.00% 0/34 • 24 Weeks
Gastrointestinal disorders Vomiting	8.3% 3/36 • Number of events 3 • 24 Weeks	5.9% 2/34 • Number of events 3 • 24 Weeks
Metabolism and nutrition disorders Weight loss	5.6% 2/36 • Number of events 3 • 24 Weeks	0.00% 0/34 • 24 Weeks
Endocrine disorders High cortisol	5.6% 2/36 • Number of events 2 • 24 Weeks	0.00% 0/34 • 24 Weeks
Endocrine disorders Low cortisol	13.9% 5/36 • Number of events 9 • 24 Weeks	8.8% 3/34 • Number of events 4 • 24 Weeks
Skin and subcutaneous tissue disorders Rash	0.00% 0/36 • 24 Weeks	5.9% 2/34 • Number of events 2 • 24 Weeks

Additional Information

Ann Davis, PhD, MPH, ABPP, Director, Center for Children's Healthy Lifestyles & Nutrition

University of Kansas Medical Center

Phone: (913) 588-1227

Email: adavis6@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place