Celiac DiseaseNCT00819819
Infant Nutrition and Risk of Celiac Disease
A study testing Gluten and Gluten free diet in people with Celiac Disease and Infant Nutrition, run by Massachusetts General Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Celiac Disease, Infant Nutrition
- What is being tested?
- Gluten and Gluten free diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Jul 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- Infants that have gluten introduced in their diet before 5-6 months of age
- Infants older than 6 months of age
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital East
Charlestown, Massachusetts, 02129
About this study
Official title: Infant Nutrition and Risk of Celiac Disease: Proposal for an Intervention, Prospective Multicenter Study
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.
Read the detailed 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.
- Conditions
- Celiac Disease, Infant Nutrition
- Being tested
- Gluten, Gluten free diet
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlutenDietary supplement
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 dietDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 Gluten containing diet | Active comparator | Gluten added to diet at 6 months per American Academy of Pediatrics recommendations Receives: Dietary Supplement: Gluten |
| 2 Gluten free diet | Active comparator | Non gluten containing food starch added to diet from 6-12 months Receives: Dietary Supplement: Gluten free diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2009 (estimated)
- Study startApr 2008
- Primary completionJul 2013
- Study completionJul 2013
Why it stopped: A similar study was conducted and subsequently published in Italy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Celiac DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessio Fasano, Massachusetts General Hospital
- Investigators
- Alessio Fasano, M.D., Principal investigator, Center for Celiac Research MGH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00819819
- Sponsor's protocol ID
- 2013P000287
- Status last verified
- Mar 2017
- First submitted
- 7 Jan 2009
- Last updated
- 22 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr. 2002 May;75(5):914-21. doi: 10.1093/ajcn/75.5.914.
PubMed 11976167Norris 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. doi: 10.1001/jama.293.19.2343.
PubMed 15900004Hoorfar 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. doi: 10.1079/bjn19930059.
PubMed 8490012Norris 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. doi: 10.1001/jama.290.13.1713.
PubMed 14519705Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev. 1999 Sep-Oct;15(5):323-7. doi: 10.1002/(sici)1520-7560(199909/10)15:53.0.co;2-p.
PubMed 10585617Damci 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. doi: 10.1046/j.1365-2362.2003.01161.x.
PubMed 12713453Meddings 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):G951-7. doi: 10.1152/ajpgi.1999.276.4.G951.
PubMed 10198339Clemente 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. doi: 10.1136/gut.52.2.218.
PubMed 12524403Watts 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. doi: 10.1073/pnas.0500178102. Epub 2005 Feb 14.
PubMed 15710870Sollid LM, Lundin KE. [Disease mechanisms in coeliac disease]. Tidsskr Nor Laegeforen. 2003 Nov 20;123(22):3230-3. Norwegian.
PubMed 14714017Gronlund 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. doi: 10.1136/fn.83.3.f186.
PubMed 11040166Kirjavainen 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. doi: 10.1136/gut.51.1.51.
PubMed 12077091
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infant Nutrition and Risk of Celiac Disease: Proposal for an Intervention, Prospective Multicenter Study
- ClinicalTrials.gov ID
- NCT00819819
- Acronym / sponsor ID
- 2013P000287
- Conditions
- Celiac Disease, Infant Nutrition
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A similar study was conducted and subsequently published in Italy.
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 9 Jan 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Gluten containing diet | Active comparator | Dietary Supplement: GlutenGluten added to diet at 6 months per American Academy of Pediatrics recommendations |
| 2 Gluten free diet | Active comparator | Dietary Supplement: Gluten free dietNon gluten containing food starch added to diet from 6-12 months |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (2 listed)
- Infants that have gluten introduced in their diet before 5-6 months of age
- Infants older than 6 months of age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlutenPurified 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. | Dietary supplement | 1 Gluten containing diet |
| Gluten free dietNon 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. | Dietary supplement | 2 Gluten free diet |
Primary outcome
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
Time frame: 5 years
Results and safety
The study was stopped early (reason given: A similar study was conducted and subsequently published in Italy.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2017.
- Background: PubMed 11976167Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr. 2002 May;75(5):914-21. doi: 10.1093/ajcn/75.5.914.
- Background: PubMed 15900004Norris 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. doi: 10.1001/jama.293.19.2343.
- Background: PubMed 8490012Hoorfar 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. doi: 10.1079/bjn19930059.
- Background: PubMed 14519705Norris 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. doi: 10.1001/jama.290.13.1713.
- Background: PubMed 10585617Funda DP, Kaas A, Bock T, Tlaskalova-Hogenova H, Buschard K. Gluten-free diet prevents diabetes in NOD mice. Diabetes Metab Res Rev. 1999 Sep-Oct;15(5):323-7. doi: 10.1002/(sici)1520-7560(199909/10)15:53.0.co;2-p.
- Background: PubMed 12713453Damci 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. doi: 10.1046/j.1365-2362.2003.01161.x.
- Background: PubMed 10198339Meddings 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):G951-7. doi: 10.1152/ajpgi.1999.276.4.G951.
- Background: PubMed 12524403Clemente 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. doi: 10.1136/gut.52.2.218.
- Background: PubMed 15710870Watts 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. doi: 10.1073/pnas.0500178102. Epub 2005 Feb 14.
- Background: PubMed 14714017Sollid LM, Lundin KE. [Disease mechanisms in coeliac disease]. Tidsskr Nor Laegeforen. 2003 Nov 20;123(22):3230-3. Norwegian.
- Background: PubMed 11040166Gronlund 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. doi: 10.1136/fn.83.3.f186.
- Background: PubMed 12077091Kirjavainen 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. doi: 10.1136/gut.51.1.51.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alessio Fasano, M.D. principal investigator
Center for Celiac Research MGH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gluten and Gluten free diet in people with Celiac Disease and Infant Nutrition, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: A similar study was conducted and subsequently published in Italy.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00819819, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2017.