EAL

CD: Villous Atrophy (2006)

Citation:

Janatuinen EK, Kemppainen TA, Pikkarainen PH, Holm KH, Kosma VM, Uusitupa MIJ, Maki M, Julkunen RJK. Lack of cellular and humoral immunological responses to oats in adults with celiac disease. Gut 2000; 46: 327-331.

PubMed ID: 10673292

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To investigate whether oats in the diets of adult patients with newly diagnosed CD would have any effect on the rate of decrease in gliadin and reticulin antibody levels, as indicators of humoral immunology or the number of intraepithelial lymphocytes (IELs), a marker of local immune response. The same variables were also measured in patients with CD in remission.

Inclusion Criteria:

From 1995 study: Age 18 or older, normal or almost normal duodenal villous architecture after GFD consumption for at least one year. Newly diagnosed subjects must have subtotal or total villous atrophy.

Exclusion Criteria:

From 1995 study: Any medical condition sufficiently serious to interfere with trial or constitute risk to patient, previous or current corticosteroid treatment for CD, history of complications of CD, neurological, cardiovascular, pulmonary, metabolic, hematological or endocrine disorder hindering participation, drug or alcohol abuse, mental impairment, lack of cooperation, any other reason for villous atrophy, diets containing oats.

Description of Study Protocol:

Recruitment

From 1995 study: All new patients with subtotal or total villous atrophy diagnosed at the Kuopio University Hospital between December 1, 1988 and December 31, 1990 were included in the study.

Design

From 1995 study: Randomized Controlled Trial.

Blinding used (if applicable)

From 1995 study: Single blinded study; examining physicians did not know diets of patients.

Intervention (if applicable)

From 1995 study: Patients randomly assigned according to sex to either the oat group or control group. Adults with CD in remission were followed for six months and 40 with newly diagnosed CD were followed for 12 months.

Statistical Analysis

From 1995 study: All analyses carried out with intention-to-treat principle. Results are presented as means±SD. Differences between groups assessed by Student's two-tailed t-test or the Mann-Whitney U test. 95% confidence intervals were calculated for the differences in the changes between the two groups.

Data Collection Summary:

Timing of Measurements

From 1995 study: Endoscopy with duodenal biopsy performed at beginning and 26 weeks. Nutritional status (BMI), symptoms and hematogical parameters measured at baseline, four, 13 and 26 weeks. Studies were repeated at 52 weeks for patients with newly diagnosed CD.
This article: Serum levels of gliadin and reticulin antibodies and intraepithelial lymphocyte (IEL) counts in intestinal mucosa examined before and after the intervention.

Dependent Variables

From 1995 study

Duodenal biopsy specimens obtained through endoscopy at the duodenal bulb and at 5-cm intervals thereafter as far down as possible, two specimens per level. Assessed as either partial, subtotal or total villous atrophy. Specimens were also measured histomorphometrically with the Quantimet 570 image analyzer.
Symptom assessments measured during three days before a visit. Abdominal pain, abdominal distention, flatulence and general well-being measured on a 100 point scale.
Nutritional status determined through interview with RD and four-day food records.
Blood samples taken after overnight fast. Blood Hgb and serum albumin, iron, calcium and RBC folate measured.

This article

Serum IgA and IgG gliadin antibodies measured by ELISA
Serum IgA R1-type reticulin antibodies determined by indirect immunofluorescence method
IELs identified and counted in specimens.

Independent Variables

From 1995 study: Oat group received products supplemented with oats; two types of gluten-free wheat starch flour mixed with an equal amount of oats, muesli containing 60% oats and rolled-oat breakfast cereal. Daily oat intake targeted at 50-70 g, and adherence checked through four-day food records. Analysis of gluten content performed at the National Food Administration in Sweden by ELISA and found to be gluten free.

Description of Actual Data Sample:

Initial N: From 1995 study: 104 adults with previous diagnosis of CD and 50 with newly diagnosed disease asked to participate. 62 patients were excluded - they did not meet inclusion criteria.
Attrition (final N): From 1995 study: 52 patients with CD in remission (9 men, 17 women in Oat group, 8 men, 18 women in Control group) and 40 patients with newly diagnosed CD (7 men, 12 women in Oat group, 5 men, 16 women in Control group). 11 patients withdrew from the study. Among patients in remission, 3 with dermatitis herpetiformis (1 in Control, 2 in Oats) reported worsening of itching. 1 patient in Oat group withdrew due to abdominal symptoms, and 2 in Control group withdrew without giving reason. Among newly diagnosed patients, 1 in Control group reported itching and 1 in Oat group had abdominal symptoms. 3 patients, 1 in Control and 2 in Oat group refused to continue.
Age (from 1995 study): Mean age for CD in remission 48±12 yrs in Oat group, 42±10 yrs in Control group. Mean age for newly diagnosed CD 42±14 yrs in Oat group, 48±11 yrs in Control group.
Ethnicity: Not mentioned.
Location (from 1995 study): Kuopio University Hospital, Finland.

Summary of Results:

	CD in Remission: 6 mos study Oats (n=26)	CD in Remission: 6 mos study Controls (n=26)	P value of difference	Newly Diagnosed CD: 1 yr study Oats (n=19)	Newly Diagnosed CD: 1 yr study Controls (n=21)	P value of difference
Anti-gliadin IgA Change	0.0 (-0.47 to 0.41)	0.0 (-0.31 to 0.03)	0.33	-0.73 (-9.9 to 0)	-0.57 (-9.38 to 0)	0.69
Anti-gliadin IgG Change	0.0 (-1.21 to 2.02)	0.0 (-2.63 to 0.86)	0.12	-7.09 (-29.85 to 0)	-2.99 (-55.2 to 0.53)	0.99
Anti-reticulin IgA Change	0 (-50 to 0)	0 (-50 to 0)	1.0	-200 (-2000 to 0)	-175 (-4000 to 5)	0.79
IEL Count Change	0.6±21.8	2.0±11.7	0.94	-23.8±23.3	-21.7±14.5	0.84

Other Findings

From 1995 study: Mean daily oat intake was 49.9±14.7 g at six months for subjects in remission, 46.6±13.3 g at 12 months for subjects with newly diagnosed disease.
The rate of disappearance of gliadin and reticulin antibodies did not differ between the diet groups in patients with newly diagnosed CD. Oats had no effect on gliadin or reticulin antibody levels in those in remission.
The number of IELs decreased similarly regardless of the diet of newly diagnosed patients, and no increase in the number of IELs was found in patients in remission with or without oats.

Author Conclusion:

In conclusion, our results show that oats used as part of an otherwise GFD in adults with CD in remission do not cause any changes in humoral or local immunological responses, as measured by levels of gliadin and reticulin antibodies or numbers of IELs. More importantly, our report shows that a GFD containing oats normalizes gliadin and reticulin antibodies as well as the number of IELs in the intestinal mucosa of newly diagnosed patients at the same rate as in patients consuming a conventional strict GFD. These results further support the conception that adult celiac patients can eat moderate amounts of oats without harmful effect.

Funding Source:

Industry:

Raisio Factories-Melia Ltd (Finland)

Food Company:

Not-for-profit

Foundation associated with industry:

In-Kind support reported by Industry:

Yes

Reviewer Comments:

So many potential subjects were excluded. They were not studying patients with severe CD requiring corticosteroid treatment.

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?	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?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	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%.)	???
	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?	???
	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)?	???
	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