Celiac Disease Screening

Our overall hypothesis is that first and second degree relatives of individuals with celiac
disease benefit from screening and diagnosis of celiac disease. Secondary hypotheses are:

1. The number needed to test and cost to benefit one person though celiac disease screening
are within acceptable ranges of 33 tested and < $10,000 spent.

2. Treatment does not lead to adverse metabolic changes.

3. Intestinal biopsy is unnecessary for accurate diagnosis in a substantial subset of
adults.

Aim 1. Determine the effect of screen detected celiac disease on health related quality of
life.

- Evaluate change in health related quality of life at one year in participants randomized
to the screen detected, early diagnosis cohort compared to the screen detected, delayed
diagnosis, clinically detected and non-celiac control cohorts.

- Evaluate change in symptoms, psychological well-being and burden of treatment at one
year in the screen detected, early diagnosis cohort compared to the screen detected,
delayed diagnosis, clinically detected and non-celiac control cohorts.

- Evaluate the cost per diagnosis and the number needed to test for the diagnosis of
individuals who will have a clinically meaningful improvement in health related quality
of life attributable to treatment of celiac disease.

Aim 2: Assess the effect of screen detected celiac disease on nutritional and metabolic
indices.

- Compare changes bone density, body mass index, Reynolds Cardiovascular Risk Score, and
nutritional indices at one year in the screen detected, early diagnosis cohort compared
to the screen detected, delayed diagnosis, clinically detected and non-celiac control
cohorts.

Aim 3: Evaluate the reliability of using serologic tests in combination with intestinal fatty
acid binding protein vs. intestinal biopsy to confirm celiac disease diagnosis in adults.

- Prospectively assess the sensitivity and specificity of a novel non-invasive celiac
diagnostic algorithm in comparison to the current gold standard of small intestinal
biopsy histology.

- Model the cost of modified, non-invasive celiac testing vs. classical testing with
endoscopic biopsy in both screen-detected and clinically identified celiac disease.

Inclusion Criteria:

- Be ambulatory, community dwelling, 18 to 80 years, inclusive

- For the screening cohort:

- Have a first or second degree family member with known biopsy-proven celiac
disease.

- Have not been on a gluten-free diet in the past 6 months

- Have not received a prior diagnosis of celiac disease at any time

- For the clinically detected cohort

- Have biopsy proven celiac disease detected based on clinical symptoms and on a
gluten free diet for less than 1 month.

Exclusion Criteria:

- For the screen detected cohort, have significantly severe symptoms (as judged by the
investigator) at screening which preclude randomization;

- Be on a gluten-free diet or have been on a gluten-free diet within the past 6 months.

- Be pregnant or planning pregnancy in the study time period

- Be taking corticosteroids or immunomodulators

- Have a history of significant concomitant gastrointestinal disease or other
comorbidity judged by the investigator to potentially interfere with study outcomes

- Be unable or unwilling to cooperate with the study protocol

- Have insufficient knowledge of English to complete study surveys