Chronic Oral Food RefusalPhase 2NCT01206478
Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age
A Phase 2 study testing Amitriptyline and Megestrol in people with Chronic Oral Food Refusal, run by Ann Davis, PhD, MPH, ABPP at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 9 months to 8 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Oral Food Refusal
- What is being tested?
- Amitriptyline and Megestrol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2010to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 months to 8 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Subjects must meet all of the following inclusion criteria:
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Kansas Medical Center
Kansas City, Kansas, 66160
Children's Hospital of New Orleans
New Orleans, Louisiana, 70118
About this study
Official title: A Phase II, Randomized-Controlled, Multicenter Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age
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.
Read the detailed description
This research study involves a study drugs called amitriptyline and megestrol. Amitriptyline might help children who have feeding problems with pain and megestrol is known to increase appetite. Amitriptyline and megestrol are liquid syrups that are given by feeding tube daily.
Amitriptyline has not been approved by the United States Food and Drug Administration (FDA) for the treatment of child with feeding problems. Amitriptyline is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for child with feeding problems. Amitriptyline is approved by the FDA for the treatment of depression.
Megestrol has not been approved by the United States Food and Drug Administration (FDA) for the treatment of children with feeding problems. Megestrol is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for children with feeding problems. Megestrol has been approved by the FDA for the treatment of adults. Though megestrol is not FDA approved to treat children with feeding problems, it is often used for this purpose.
Megestrol and Amitriptyline both affect the nerve cells that carry pain sensations to and from the brain. Both drugs reduce the intensity of the pain signals going to the part of the brain that feels pain. Each drug attaches to the nerve cell but at separate spots on the nerve cell so pain can be better managed.
- Conditions
- Chronic Oral Food Refusal
- Being tested
- Amitriptyline, Placebo, Megestrol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmitriptylineDrug
Amitriptyline 1 mg/kg once daily at bedtime.
PlaceboDrug
Placebo (looks like study drug but has no active ingredients) once daily at bedtime.
MegestrolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Amitriptyline plus Megestrol | Experimental | Amitriptyline once daily at bedtime plus megestrol starting at visit 2 Receives: Drug: Amitriptyline; Drug: Megestrol |
| Placebo plus Megestrol | Active comparator | Matching placebo once daily at bedtime plus megestrol starting at visit 2 Receives: Drug: Placebo; Drug: Megestrol |
What is being measured
The primary outcome is the main question the study is designed to answer.
% 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.
Measured: baseline, 24 weeks
Secondary outcomes (1)
Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores
Non-communicating Children's Pain Checklist - Revised (NCCPC-R) used to measure outcome. The NCCPC-R is a 30 item measure intended to assess pain in children who are unable to speak because of cognitive or physical impairments. There are 7 sub-scales including vocal, social, facial, activity, body/limbs, physiological, and eating/sleeping. Each question has a potential score of 0 to 3. Scores are totaled for each sub-scale. Sub-scale scores are then added together for the Total Score. Total Scores can range from 0 to 90. The higher the score, the higher level of pain indicated by the child. This measure was completed by parents at week 0, week 10, and week 24.
Measured: baseline, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2010 (estimated)
- Study startAug 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Oral Food RefusalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ann Davis, PhD, MPH, ABPP
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Ann Davis, PhD, MPH, ABPP, University of Kansas Medical Center
- Investigators
- Ann Davis, Ph.D., MPH, ABPP, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01206478
- Sponsor's protocol ID
- 12261
- Other IDs
- R21HD066629
- Status last verified
- May 2016
- First submitted
- 20 Sep 2010
- Last updated
- 15 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33339464Davis 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.
PubMed 26947568
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized-Controlled, Multicenter Trial of Amitriptyline for Chronic Oral Food Refusal in Children 9 Months to 8 Years of Age
- ClinicalTrials.gov ID
- NCT01206478
- Acronym / sponsor ID
- 12261
- Conditions
- Chronic Oral Food Refusal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Ann Davis, PhD, MPH, ABPPUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Aug 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 21 Sep 2010 (estimated)
- Results
- Posted 15 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This research study involves a study drugs called amitriptyline and megestrol. Amitriptyline might help children who have feeding problems with pain and megestrol is known to increase appetite. Amitriptyline and megestrol are liquid syrups that are given by feeding tube daily.
Amitriptyline has not been approved by the United States Food and Drug Administration (FDA) for the treatment of child with feeding problems. Amitriptyline is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for child with feeding problems. Amitriptyline is approved by the FDA for the treatment of depression.
Megestrol has not been approved by the United States Food and Drug Administration (FDA) for the treatment of children with feeding problems. Megestrol is an investigational drug that is being studied to find out what the side effects are, and whether or not the product works for children with feeding problems. Megestrol has been approved by the FDA for the treatment of adults. Though megestrol is not FDA approved to treat children with feeding problems, it is often used for this purpose.
Megestrol and Amitriptyline both affect the nerve cells that carry pain sensations to and from the brain. Both drugs reduce the intensity of the pain signals going to the part of the brain that feels pain. Each drug attaches to the nerve cell but at separate spots on the nerve cell so pain can be better managed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amitriptyline plus Megestrol | Experimental | Drug: Amitriptyline, Drug: MegestrolAmitriptyline once daily at bedtime plus megestrol starting at visit 2 |
| Placebo plus Megestrol | Active comparator | Drug: Placebo, Drug: MegestrolMatching placebo once daily at bedtime plus megestrol starting at visit 2 |
Who may qualify
- Ages
- 9 months to 8 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmitriptylineAmitriptyline 1 mg/kg once daily at bedtime. | Drug | Amitriptyline plus Megestrol |
| PlaceboPlacebo (looks like study drug but has no active ingredients) once daily at bedtime. | Drug | Placebo plus Megestrol |
| MegestrolAt 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. | Drug | Amitriptyline plus Megestrol, Placebo plus Megestrol |
Primary outcome
% Calories Taken Orally
Time frame: baseline, 24 weeks
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.
1 secondary outcome
Change in Non-communicating Children's Pain Checklist - Revised (NCCPC-R) Scores
Time frame: baseline, 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33339464Garcia 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.
- Derived from this study: PubMed 26947568Davis 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann Davis, Ph.D., MPH, ABPP principal investigator
University of Kansas Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amitriptyline and Megestrol in people with Chronic Oral Food Refusal, run by Ann Davis, PhD, MPH, ABPP at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
% Calories Taken Orally (time frame: baseline, 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01206478, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2016.