EAL

CD: Oats and Gluten Intolerance (2005)

Citation:

Lundin KEA, Nilsen EM, Scott HG, Loberg EM, Gjoen A, Bratlie J, Skar V, Mendez E, Lovik A, Kett K. Oats induced villous atrophy in celiac disease. Gut 2003; 52: 1649-1652.

PubMed ID: 14570737

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 further investigate oat consumption by celiac patients.

Inclusion Criteria:

All diagnosed with CD based on duodenal villous atrophy, followed by clinical and histological improvement on a standard GFD.

Exclusion Criteria:

None defined.

Description of Study Protocol:

Recruitment

19 CD patients agreed to start the challenge.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

No blinding used.

Intervention (if applicable)

Adult CD patients challenged with 50 g oats/day for 12 weeks.

Statistical Analysis

Data was descriptive in nature and not statistically analyzed.

Data Collection Summary:

Timing of Measurements

Serological testing, gastroduodenoscopy and C-D-xylose breath test performed before and after the challenge. GI symptoms and food intake measured before, during and at end of study at 12 weeks.

Dependent Variables

Serological testing: IgA AGA, EMA and tTG analyzed in routine lab
Biospies obtained with jumbo forceps through gastroduodenoscopy. Biopsies were scored histologically according to Marsh classification. Levels of mRNA specific for interferon gamma determined by reverse transcription-polymerase chain reaction analysis.
GI symptoms: Measurement not described
Food intake: Measurement not described.

Independent Variables

Target for daily oat intake was 50 g. Oats in study came from one manufacturer and were tested for purity by ELISA, western blot and mass spectrometry.

Description of Actual Data Sample:

Initial N: 19 adult CD patients: 17 female, two male
Attrition (final N): 18 adults completed the study. One patient withdrew after two weeks due to GI symptoms and a general feeling of unwellness. A second patient presented more severe GI symptoms with diarrhea and bloating, which resolved towards the end of the challenge. 15 patients returned for follow-up 1.5 years after eating oats at their own will.
Age: Not mentioned.
Ethnicity: Not mentioned
Location: Norway.

Summary of Results:

Other Findings

Through oat purity testing, the gluten content in five of the samples was estimated to lie between <1.5 ppm and 23 ppm.
Oats were well tolerated by most patients, but several reported initial abdominal discomfort and bloating. Small intestinal biopsies taken after the oat challenge showed either unchanged or improved histology, with the exception of one patient who developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Two of the samples with <1.5 ppm were from the oats eaten by the oat intolerant patient. Clinically, she is a well treated but sensitive CD patient.
Levels of IgA AGA were unchanged during the challenge. All patients had a negative IgA EMA before and after the challenge. Levels of IgA-anti-tTG were below the reference level before and after the challenge in all patients. Five of the patients showed positive levels of interferon gamma mRNA after challenge. With the exception of the oat intolerant subject, the other four subjects had histologically normal or near normal mucosa.
After 1.5 years, 12 of 15 patients regularly consumed oats, but at a level less than 50 g/day. Small intestinal histology was still satisfactory and all had normal serology.

Author Conclusion:

The present data support the notion that most CD patients tolerate oats in their diet. Contamination of commercial oats by other cereals is a problem and celiacs should select oats from manufacturers that are devoted to producing oats without such contaminants. However, the finding that even pure oats can induce villous atrophy in one CD patient raises some concern.

Funding Source:

Industry:

Regal, Freia Chokolade Fabriks Medicinske Fond,

Food Company:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Small sample size. Samples consumed by the oat-intolerant patient were found to be uncontaminated. Did not compare actual oat intake to target intake.

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?	???
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	???
	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?		Yes
	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?	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?		???
	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?	???
	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?	N/A
	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	No
	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?	No
	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