Results Summary
What was the research about?
Eosinophilic esophagitis, or EoE, is a health problem that occurs when the esophagus, which connects the mouth to the stomach, becomes inflamed with allergy-related cells called eosinophils. EoE symptoms include nausea, vomiting, stomach pain, and having a hard time swallowing.
For children with EoE, treatment can include a restrictive diet, which means removing one or more types of food from what they eat. They can also take medicine. Both treatments can work, but they may also cause problems. For example, limiting a child’s diet can affect growth or be hard to manage. Medicine can have harmful side effects.
This study had two parts. First, the research team compared two diets:
- A diet that removed one food: milk
- A diet that removed four foods: milk, egg, wheat, and soy
Then, the research team changed the treatment for children whose restrictive diet wasn’t improving symptoms, to see if the change would help.
What were the results?
At the end of the first part of the study, both diets resulted in improved symptoms, quality of life, and well-being. Symptoms improved more in children who removed four foods from their diet compared with children who removed only one food. In addition, 40 percent of children in both groups showed remission. In remission, few allergy-related cells are found in the esophagus.
Too few children were in the second part of the study to make any conclusions.
Who was in the study?
The study included 63 children, ages 6 to 17, who had EoE and were receiving care at specialty clinics across the United States. Of these children, 87 percent were white, 8 percent were black, and 5 percent were of another race; 11 percent were Hispanic. The average age was 12, and 67 percent were boys.
What did the research team do?
In the first part of the study, the research team assigned children, by chance, to one of the two diets. Children followed their assigned diet for three months. Children who didn’t improve changed their treatment for the next three months. Those who had removed only milk from their diet also removed egg, wheat, and soy. Children who had removed four foods started taking medicine.
At the start and end of each part of the study, children or their parents answered questions about symptoms, quality of life, well-being, and if the children had followed their diets.
Organizations supporting children with EoE and the families of children with EoE gave input on this study.
What were the limits of the study?
The research team didn’t enroll as many children in the study as they had planned. Results may have differed if more children had taken part. Also, 60 percent of children didn’t continue with the second part of the study. Children and their parents knew which treatment group they were in; this information may have affected how they reported symptoms.
Future research studies could look at the effect of cutting out only foods with uncooked milk, such as cheese and yogurt, and allowing foods in which the milk is cooked. Studies could also test removing six types of food from the diet when removing four types of food doesn’t help. In addition, researchers could find ways to make it easier for children to take part in the research studies.
How can people use the results?
Doctors, children, and their caregivers can use these results when considering different diets to treat EoE, especially when thinking about trying a diet that first removes milk products.
Professional Abstract
Objective
To compare the effectiveness of two restrictive diets on improving symptoms, quality of life, patient-reported health outcomes, and rates of remission in children with eosinophilic esophagitis (EoE)
Study Design
| Design Elements | Description |
|---|---|
| Design | Randomized controlled trial |
| Population | 63 children ages 6–17 with active EoE |
| Interventions/ Comparators |
|
| Outcomes |
Primary: change in overall symptoms score Secondary: histologic remission, quality of life score, PROMIS® measures of psychological and emotional well-being |
| Timeframe | 6-month follow-up for primary outcomes |
This randomized controlled trial compared the effectiveness of two restrictive diets on improving symptoms in children with EoE. In the one-food-elimination diet (1FED) group, children followed a diet that eliminated milk and foods containing milk. In the four-food-elimination diet (4FED) group, children followed a more restrictive diet that eliminated foods containing milk, egg, wheat, and soy. Researchers also determined the effectiveness of swallowed glucocorticoid (SGC) medication in children who did not improve on 4FED after three months.
Researchers randomly assigned 63 children with EoE, ages 6 to 17, receiving treatment at 10 EoE specialty centers across the United States to one of the two diets. Of these children, 87% were white, 8% were black, and 5% were of another race; 11% were Hispanic. The average age was 12, and 67% were male.
In phase one of the study, the children received three months of treatment with one of the diets. In phase two, children who did not respond to 1FED changed to 4FED, and children who did not respond to 4FED received SGC for three months.
At baseline and at the end of each phase, researchers assessed study outcomes. Children and their parents completed a set of validated instruments and surveys from the Patient-Reported Outcomes Measurement Information System (PROMIS®) to assess children’s pain, health, and function. Researchers conducted phone surveys to measure diet compliance, adverse events, and food intake 2 weeks and 11 weeks after baseline. Each child also underwent an endoscopy to assess histologic remission at the end of each phase.
EoE advocacy groups representing children with EoE and their families informed the study design and implementation.
Results
After phase one, overall symptom scores, health-related quality of life, and psychosocial and emotional well-being improved for children on both diets. Compared with the 1FED diet, the change in symptom score in the 4FED diet was significantly greater (p=0.041).
Forty percent of children on both diets achieved histologic remission, and 20% of children on both diets achieved complete (very low eosinophil counts) remission. The study found no significant differences in histology between the groups.
Too few children were in phase two of the study to draw any conclusions.
Limitations
The study did not achieve the planned sample size. Further, 60% of the children did not participate in the second part of the study, limiting the ability to draw conclusions from phase two findings. The study was unblinded, which could have affected subjective patient-reported outcomes.
Conclusions and Relevance
Although 4FED showed a small advantage over 1FED in improving some symptoms, both diets achieved similar histologic remission rates and were similar in improving symptoms, quality of life, and psychosocial and emotional well-being after three months. As such, 1FED may be a viable and less restrictive treatment option for some children with EoE and an option for first line therapy.
Future Research Needs
Future research could examine whether clinicians can predict which patients will respond to 1FED. To generate adequate sample size, researchers may need to modify entry exclusion criteria and address concerns about participation. Studies could also compare the value of a six-food-elimination diet (eliminating peanuts/tree nuts and fish/shellfish in addition to 4FED exclusions) versus medication in achieving remission after 4FED failure.
Final Research Report
View this project's final research report.
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:
- Reviewers asked whether the researchers collected baseline characteristics for participants that may have affected their adherence to the behavior change intervention. The researchers responded that they did not collect demographic characteristics, such as education and income that might have provided such information. However, they did add some discussion of potential factors that may have contributed to participants’ compliance with the diet, backing up their postulations with previous research.
- Because researchers enrolled far fewer patients in the study than planned, reviewers asked whether that compromised statistical power to detect clinically important differences. Reviewers suggested conducting another power analysis to determine small-to-medium effects in the primary outcome measure. The researchers said they did not feel the need to conduct the additional power analysis because they detected a difference between groups on the primary outcome. For secondary aims, the researchers acknowledged the study was underpowered to detect small-to-moderate clinically important differences between groups. The researchers addressed the limitations in identifying small-to-moderate differences within treatment group due to smaller-than-expected sample size also.
- Reviewers asked for additional detail on how researchers assigned study subjects to groups, noting the unequal number assigned to the two interventions. The researchers added details about the randomization process to the methods. Because of the low recruitment levels and because when assigning subjects to different protocols, factors such as subjects’ age and gender were taken into consideration, allocations became uneven.
- Reviewers questioned the use of symptoms instead of histology to score the primary outcome. The researchers noted that PCORI had asked that changes in symptoms be the primary outcome in the initially approved research plan, perhaps because symptoms are of greater interest to patients. The researchers added information about this to the background and methods sections. They also noted that a larger sample size would have been needed to detect differences between the two diets if they had used both histology and symptoms as measures, instead of either alone.