Infant Nutrition and Risk of Celiac Disease

Celiac Disease Clinical Trial

Official title:

Infant Nutrition and Risk of Celiac Disease: Proposal for an Intervention, Prospective Multicenter Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00819819
• Other study ID #: 2013P000287
• Status: Terminated
• Phase: N/A
• First received: January 7, 2009
• Last updated: March 21, 2017
• Start date: April 2008
• Est. completion date: July 2013

Study information

• Verified date: March 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will identify a cohort of infants at risk for celiac disease that can be followed on a long term basis for investigating the natural history the celiac disease based on the pattern of early nutrition. The study will investigate possible early feeding patterns including the timing of introduction to gluten that may protect at least in part from CD development in at risk infants.

Description:

From weaning to age 12 months the clinical data, the adherence to the dietary protocol and the amount of intervention baby-food ingested will be checked every month. Following investigations will be performed at the time of recruitment, at time of weaning and at 12, 18, 24, 30,36, 42, 48, 54 and 60 months by taking a sample of blood (maximum 4 ml) from infants (a) quick test for IgA anti-tTG abs determination (few drops); (b) conventional ELISA for serum IgA and IgG anti-tTG determination (0.4 ml);(c) serum zonulin determination (0.1 ml); (e) serum sample for T1D-related autoantibodies (0.25 ml); (f) serum sample to be stocked in the sera bank (0.25 ml); (g) whole blood sample in EDTA for validation of the quick tests (0.5 ml). All the sera samples will be frozen, stored at -20 °C and sent (boxed in dry ice) in blocks to the centre responsible for the determinations every 2 months. Cases positive for the quick-test for anti-tTG the serum sample will be frozen and immediately shipped for confirmatory determination.

If infants develop symptoms during the intervention period (6 to 12 months) the group to which infant belongs will be decoded. Infants belonging to group A (on a gluten-containing diet) presenting symptoms suggestive of CD will undergo a complete diagnostic work-up for CD. These events will be reported in a form. After age 1 year, infants developing symptoms suggestive of active CD (chronic diarrhea, failure to thrive, etc) in-between the scheduled visits will undergo a supplementary serological investigation. A small intestinal biopsy will be recommended in cases showing either serum anti-tTG abs higher than the cut-off or IgG-AGA higher than cut-off in infants with selective IgA deficiency. (Standard medical care and not part of research).

The evolution of the composition of the intestinal microbiota will be evaluated in both groups at 7d, 30d, 4-6 months (prior to weaning), 12,18,24,30,36, 42, 48, 54 and 60 months. The bacterial composition of stool will also be analyzed in a sub-sample of children developing active CD and in non-CD controls. All patients who develop CD will continue in the study.

Definitions:

Active CD: Children showing positive serology and signs of immune-mediated damage of the small intestinal mucosa on biopsy (ranging from isolated increase of intraepithelial lymphocytes to villous atrophy with crypt hypertrophy.)

CD serological autoimmunity positive: Children positive for IgA anti-tTG abs on two consecutive occasions.

Disruption of the small intestinal barrier: Children with an increased ratio of serum lactulose/mannitol with or without increased levels of serum zonulin.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Months

Eligibility

Inclusion Criteria:

• Newborns and infants less than 6 months of age

• First-degree relatives of patients affected with biopsy-proven CD

• On exclusive milk diet (breast milk or formula)

Exclusion Criteria:

• Infants that have gluten introduced in their diet before 5-6 months of age

• Infants older than 6 months of age

Related Conditions & MeSH terms

• Celiac Disease
• Infant Nutrition

Intervention

Dietary Supplement:
• Gluten
Purified gluten from exaploid wheat introduced per American Academy of Pediatric Recommendations. Three grams from 6-9 months and 5 grams from 9-12 months. The 3-5 grams represents the mean daily intake of gluten during the second half of the first year in infants of different countries.
• Gluten free diet
Non gluten containing starch added to diet. Three grams from 6-9 months and 5 grams from 9-12 months. After the age of 1 year all children will be allowed age appropriate unrestricted diet.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital East	Charlestown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (12)

Clemente MG, De Virgiliis S, Kang JS, Macatagney R, Musu MP, Di Pierro MR, Drago S, Congia M, Fasano A. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003 Feb;52(2):218-23. — View Citation

Damci T, Nuhoglu I, Devranoglu G, Osar Z, Demir M, Ilkova H. Increased intestinal permeability as a cause of fluctuating postprandial blood glucose levels in Type 1 diabetic patients. Eur J Clin Invest. 2003 May;33(5):397-401. — View Citation

Funda DP, Kaas A, Bock T, Tlaskalová-Hogenová H, Buschard K. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev. 1999 Sep-Oct;15(5):323-7. — View Citation

Grönlund MM, Arvilommi H, Kero P, Lehtonen OP, Isolauri E. Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months. Arch Dis Child Fetal Neonatal Ed. 2000 Nov;83(3):F186-92. — View Citation

Hoorfar J, Buschard K, Dagnaes-Hansen F. Prophylactic nutritional modification of the incidence of diabetes in autoimmune non-obese diabetic (NOD) mice. Br J Nutr. 1993 Mar;69(2):597-607. — View Citation

Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr. 2002 May;75(5):914-21. — View Citation

Kirjavainen PV, Arvola T, Salminen SJ, Isolauri E. Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning? Gut. 2002 Jul;51(1):51-5. — View Citation

Meddings JB, Jarand J, Urbanski SJ, Hardin J, Gall DG. Increased gastrointestinal permeability is an early lesion in the spontaneously diabetic BB rat. Am J Physiol. 1999 Apr;276(4 Pt 1):G951-7. — View Citation

Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, Emery LM, Sokol RJ, Erlich HA, Eisenbarth GS, Rewers M. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. JAMA. 2005 May 18;293(19):2343-51. — View Citation

Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, Erlich HA, Rewers M. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA. 2003 Oct 1;290(13):1713-20. — View Citation

Sollid LM, Lundin KE. [Disease mechanisms in coeliac disease]. Tidsskr Nor Laegeforen. 2003 Nov 20;123(22):3230-3. Norwegian. — View Citation

Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the primary prevention of early onset celiac disease and related autoimmunity phenomena by comparing the frequency of disease development according to two different patterns of gluten introduction in at risk infants		5 years

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