EAL

CD: Oats and Gluten Intolerance (2005)

Citation:

Hoffenberg EJ, Haas J, Drescher A, Barnhurst R, Osberg I, Bao F, Eisenbarth G. A trial of oats in children with newly diagnosed celiac disease. J Pediatr 2000; 137: 361-6.

PubMed ID: 10969261

Study Design:

Non-Randomized Controlled Trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To evaluate the clinical, histologic and serologic responses in children with newly diagnosed CD who are starting a GFD with oats.

Inclusion Criteria:

Children under 18 years with CD diagnosis within three months, following a GFD. Diagnosis of CD required a positive tTG titer plus characteristic features of CD on small bowel biopsy specimen. In addition, at least one sign or symptom suggestive of CD had to be present on the study questionnaire.

Exclusion Criteria:

Excluded if they had IgA deficiency or any other immunodeficiency or if they had another illness affecting small bowel histology, such as Crohn's disease or allergy to milk or soy protein. Children were withdrawn if symptoms of CD did not improve or worsened. Subjects with a Marsh classification of 1 (normal mucosal architecture but increased IEL count) not enrolled.

Description of Study Protocol:

Recruitment

Children were recruited from the clinical practice of the section of pediatric gastroenterology at University of Colorado and from a study prospectively screening children with a genetic risk of CD.

Design

Nonrandomized clinical trial.

Blinding used (if applicable)

No blinding used.

Intervention (if applicable)

10 children with newly diagnosed CD consumed oats for six months.

Statistical Analysis

Comparisons made by using nonparametric Wilcoxon signed rank test. Data are presented as mean±SD.

Data Collection Summary:

Timing of Measurements

Small bowel histomorphology (injury score, IEL count) and anti-tissue transglutaminase IgA antibody titer measured at beginning of study and after six months. Symptom reduction and measures of growth and nutrition were also evaluated. Symptom questionnaire was administered at study entry and monthly until the end of the study.

Dependent Variables

Small bowel biopsy specimens obtained by Carey capsule or upper GI endoscopy with two to four biopsies of distal duodenum. Histologic evaluation performed according to Marsh classification, IEL counts.
Nutritional assessment: Height, weight, mid-arm circumference and triceps skinfold measurements
Blood samples obtained after four hours fasting. Serum anti-tissue transgluatminase, alpha-tocopherol to lipids ratio, RBC folate, Hgb, Fe and Zn measured.
Symptom questionnaire ascertained subjective presence or absence of chronic diarrhea, abdominal pain, abdominal distention, vomiting, constipation, irritability, flatulence or gas, poor weight gain, short stature or edema.

Independent Variables

Subjects were supplied with "maple and brown sugar flavored instant oatmeal" for consumption. Random samples of the oatmeal were tested for gluten contamination by ELISA. In one of five samples, gliadin was detected. Parents recorded child's oat intake in a daily diary.

Description of Actual Data Sample:

Initial N: Of 25 children receiving diagnosis of CD, 13 children entered study.
Attrition (final N): 10 children completed the study, five male, five female. Three were dropped due to admitted noncompliance with the GFD or with oat intake diaries.
Age: 6.8±4.0 years
Ethnicity: Eight children were white, one child was Hispanic, one child was African-American.
Location: University of Colorado School of Medicine.

Summary of Results:

Subject	tTG titer: Entry	tTG titer: Exit	Biopsy Score: Entry	Biopsy Score: Exit	IEL Count: Entry	IEL Count: Exit	Number of Symptoms: Entry	Number of Symptoms: Exit
1	0.745	0.029	3	2	32	20	6	4
2	0.074	0.057	2	0	29	13	2	1
3	0.804	0.102	3	2	48	17	4	1
4	0.400	0.099	3	2	51	24	1	1
5	0.416	0.020	3	1	30	25	3	1
6	0.437	0.144	3	0	38	12	7	2
7	0.135	0.127	3	3	54	29	7	1
8	1.816	0.095	3	0	31	16	7	1
9	0.339	0.132	3	3	15	8	6	7
10	0.346	0.019	3	0	54	12	4	0
Mean±SD	0.551±0.499	0.082±0.048	2.9±0.3	1.3±1.3	38±13	18±7	5±2	2±2

Other Findings

Intake of oats was 24±12 g/day or 1.2±0.9 g/kg body weight/day.
Compared with the start of the study, at completion there was a significant decrease in biopsy score (P<0.01), IEL count (P<0.005), anti-tissue transglutaminase IgA antibody titer (P<0.01) and number of symptoms (P<0.01). There was no difference in anthropometric or biochemical measures of growth and nutrition.

Author Conclusion:

In conclusion, 10 children with newly diagnosed CD safely added an oat cereal product on initiation of a GFD. This study supports the short-term inclusion of oats in the diet of children beginning a GFD. Long-term studies are needed to determine the safety of oats, as well as studies on methods to improve long-term adherence to a GFD.

Funding Source:

Government:

NIH, NIDDK, NCRR

Industry:

ConAgra Foods

Food Company:

University/Hospital:

Children's Hospital Research Institute

In-Kind support reported by Industry:

Yes

Reviewer Comments:

Small sample size. Of 25 newly diagnosed children, only 13 entered study. Possible oat contamination given results of random testing.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		???
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	N/A
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	N/A
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes