CD: Villous Atrophy (2006)
Hogberg L, Laurin P, Falth-Magnusson K, Grant C, Grodzinsky E, Jansson G, Ascher H, Browaldh L, Hammersjo JA, Lindberg E, Myrdal U, Stenhammar L. Oats to children with newly diagnosed celiac disease: a randomized double blind study. Gut 2004; 53:649-654.PubMed ID: 15082581
To determine if children with CD tolerate oats in their GFD.
Aged less than 18 years, small bowel biopsy showing enteropathy, good understanding of Swedish.
Excluded if inclusion criteria not met.
- 116 children recruited from eight Swedish pediatric clinics, from April 1998 to September 2001.
- Randomized double blind multicenter study.
Blinding used (if applicable)
- Study was double blind.
Intervention (if applicable)
- Children randomized to one of two groups: One given a standard GFD (GFD-Std, n=59) and one given a GFD with additional wheat free oat products (GFD-Oats, n=57) for a period of one year.
- Results presented as mean (SD) or median (range). Differences between groups assessed by Student's two-tailed t-test or the Mann-Whitney U-test. The chi-square test (two-tailed) was used to analyze differences in the frequency between study groups.
Timing of Measurements
- Small bowel biopsy performed at beginning and end of study. Serum IgA antigliadin (AGA), antiendomysium (EMA) and antitissue transglutaminase (TGA) antibodies monitored at zero, three, six and 12 months. Oat product intake monitored for first month of study and thereafter for the week prior to clinic visits at three, six, nine and 12 months.
- Small bowel biopsy performed by peroral suction capsule obtaining one or two specimens from the distal duodenum or proximal jejunum and examined by a local pathologist. Assessed as either partial, subtotal or total villous atrophy and Marsh classification used. Counts of intraepithelial lymphocytes (IELs) also completed on biopsy specimens with restored mucosa structure.
- Serum IgA AGA detected through ELISA
- Serum IgA and IgG EMA titres measured by indirect immunofluorescence microscopy
- Serum IgA TGA titre measured through ELISA kit Celikey
- Total serum IgA through routine nephelometric assay.
- Oats were specially grown, milled and packaged so as not to become contaminated, and were tested by ELISA to ensure absence of gluten contamination. To ensure blinding, oats mixed with otherwise gluten free products. Daily oat intake targeted at 25-50 g. Parents of subjects were asked to monitor oat product intake and oat intake was calculated by a dietitian.
- Initial N: 116 children with newly diagnosed symptomatic CD, male:female ratio of 1:1.4
- Attrition (final N): 93 subjects completed the study (80%). Most common reason for withdrawal was inability to follow the diet. In GFD-Std group, seven of 59 (11%) withdrew from study, two having GI symptoms. In GFD-Oats group, 15 of 57 (26%) withdrew, six due to symptoms: One subject had no catch-up growth and was withdrawn by MD, other five subjects reported abdominal pain or diarrhea. Significantly more children in the younger age group (under two years) withdrew (p=0.01).
- Age: Mean age of 6.5 years (median 6.0, range 8 months - 17.5 years)
- Ethnicity: Swedish
- Other relevant demographics: Seven children had diabetes mellitus, three of whom were in GFD-Oats. Six other subjects had IgA deficiency, one of them in GFD-Oats. The only subject with Down's Syndrome had GFD-Std.
- Anthropometrics: Difference in withdrawal frequency found to not be significant (p=0.08).
- Location: Eight Swedish pediatric clinics.
|GFD: Oats >8 g
Difference between GFD-Oats & GFD-Std, GFD-Oats >8 g & GFD-Std
|Subjects with Enteropathy||0 subjects||0 subjects||2 subjects||p=0.50, p=0.51|
IEL Count (per 100 enterocytes)
|16 (4.5) [6-26]||16 (4.0) [9-24]||16 (5.0) [3-29]||p=0.84, p=0.94|
- Median (range) amount of oats ingested in the GFD-Oats group (n=42) was 15 g (five to 40 g) at the six-month control and 15 g (zero to 43 g) at the 12-month control. Since some GFD-Oats subjects consumed very small amounts of oats toward the end of the study year, the GFD-Oats group was divided into two subgroups: Those consuming at least eight g/oats daily (n=34) and those consuming less than eight g/oats daily (n=8).
- Regarding the frequency of positive IgA AGA, no significant difference was found between the study groups (specific values not provided).
- Regarding total serum IgA, 2 patients with values below 0.05 g/l were negative for all 3 serological markers.
In conclusion, this randomized double blind study provides evidence that the presence of moderate amounts of oats in a GFD in children with CD does not prevent clinical or small bowel mucosal healing or humoral immunological downregulation. This finding is in accordance with previous open studies in celiac children and adults and indicates that oats can be safely included in a GFD for the majority of children with CD. To confirm this, long term studies of the effects of oats in celiac children are needed.
|Government:||Swedish Research Council|
|In-Kind support reported by Industry:||Yes|
High withdrawal frequency in the GFD-Oats group, with celiac symptoms in six of the 15 withdrawals. Average oat intake of 15 g was below the targeted intake of 25-50 g. Some in the GFD-Oats group were not eating any oats at one year.
Quality Criteria Checklist: Primary Research
|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|
|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?||Yes|
|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?||Yes|
|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?||Yes|
|3.||Were study groups comparable?||???|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||No|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||Yes|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||Yes|
|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%.)||Yes|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||Yes|
|4.4.||Were reasons for withdrawals similar across groups?||No|
|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?||Yes|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||Yes|
|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.)||Yes|
|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?||Yes|
|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?||Yes|
|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|