EAL

CD: Villous Atrophy (2006)

Citation:

Janatuinen EK, Pikkarainen PH, Kemppainen TA, Kosma VM, Jarvinen RMK, Uusitupa MIJ, Julkunen RJK. A comparison of diets with and without oats in adults with celiac disease. N Engl J Med 1995; 333: 1033-7.

PubMed ID: 7675045

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 adults with CD in remission could consume oats without impairment to their condition; and whether patients with newly diagnosed CD could be treated with a diet containing oats.

Inclusion Criteria:

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:

Any medical condition sufficiently serious to interfere with the 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 or diets containing oats.

Description of Study Protocol:

Recruitment

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

Randomized Controlled Trial.

Blinding used (if applicable)

Single blinded study: Examining physicians did not know diets of patients.

Intervention (if applicable)

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

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

Endoscopy with duodenal biopsy performed at beginning and 26 weeks. Nutritional status (BMI), symptoms and hematological parameters measured at baseline, four, 13 and 26 weeks. Studies were repeated at 52 weeks for patients with newly diagnosed CD.

Dependent Variables

Duodenal biopsy specimens obtained through endoscopy at the duodenal bulb and at five-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.
Blood samples taken after overnight fast. Blood Hgb and serum albumin, iron, calcium and RBC folate measured.
Nutritional status determined through interview with RD and four-day food records.

Independent Variables

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 peformed at the National Food Administration in Sweden by ELISA and found to be gluten free.

Description of Actual Data Sample:

Initial N: 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): 52 patients with CD in remission (nine men, 17 women in Oat group; eight men, 18 women in Control group) and 40 patients with newly diagnosed disease (seven men, 12 women in Oat group; five men, 16 women in Control group). 11 patients withdrew from the study. Among patients in remission, three with dermatitis herpetiformis (one in Control; two in Oats) reported worsening of itching. One patient in the Oat group withdrew due to abdominal symptoms and two in the Control group withdrew without giving reason. Among newly diagnosed patients, one in the Control group reported itching and one in the Oat group had abdominal symptoms. Three patients, one in Control and two in the Oat group, refused to continue.
Age: Mean age for CD in remission 48±12 years in Oat group, 42±10 years in Control group. Mean age for newly diagnosed CD 42±14 years in Oat group, 48±11 years in Control group.
Ethnicity: Not mentioned.
Location: Kuopio University Hospital, Finland.

Summary of Results:

	CD in Remission: 6 months study Oats (n=26)	CD in Remission: 6 months study Controls (n=26)	P value of difference	Newly Diagnosed CD: 1 year study Oats (n=19)	Newly Diagnosed CD: 1 yr study Controls (n=21)	P value of difference
BMI Change	0.1±0.8	0.4±0.8	0.09	0.7±1.3	1.0±1.1	0.47
Symptom Score Change	6.7±17.5	2.1±10.8	0.45	-8.2±26.6	-8.4±22.7	0.78
Hgb Change	-0.1±0.7	-0.2±0.5	0.44	0.1±1.0	0.0±1.2	0.78
Iron Change	13.1±38.4	-15.1±52.0	0.09	0.34±39.4	0.0±38.4	0.55
Ca Change	0.1±0.5	-0.1±0.4	0.07	0.2±0.4	0.2±0.5	0.81
RBC Folate Change	2.2±72.8	-14.8±56.4	0.21	71.3±56.9	60.0±68.0	0.90
Albumin	0.0±0.5	0.0±0.3	0.70	-0.3±0.6	-0.2±0.4	0.5
Villous Atrophy Change (All Samples)	0.01±0.36	-0.06±0.31	0.53	-1.07±0.58	-1.2±0.42	0.74
Histomorphometric Index Change	0.0±0.003	0.0±0.003	0.85	0.004±0.002	0.004±0.003	0.82
Mononuclear cell infiltration change	-0.05±0.45	0.04±0.54	0.58	-1.25±0.58	-1.14±0.55	0.51

Other Findings

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 oat and control groups did not differ significantly in nutritional status, symptoms or laboratory measures. Patients in remission, regardless of diet, did not have worsening architecture of duodenal villi or increased mononuclear cell infiltration.
All patients with new diagnoses were in remission at one year, except for one patient in the Control group.

Author Conclusion:

In conclusion, moderate amounts of oats can be included in a GFD in adult patients with CD in remission and a conventional celiac diet containing oats can allow the intestinal mucosa of patients with newly diagnosed disease to heal. Since we excluded patients with severe CD, we cannot make recommendations about the use of oats in their diets.

Funding Source:

Industry:

Raisio Factories-Melia Ltd (Finland)

Food Company:

University/Hospital:

Kuopio University Hospital (Finland), Tampere University Hospital (Finland)

Not-for-profit

Foundation associated with industry:

In-Kind support reported by Industry:

Yes

Reviewer Comments:

This is the original study population used in additional publications by Janatuinen et al. Patients with severe CD (requiring corticosteroid therapy) were excluded. Of 11 withdrawals, six were in the Oat group.

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