Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity (EDIA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Helsinki University
Sponsor:
Collaborators:
University of Turku
National Institute for Health and Welfare, Finland
Tampere University Hospital
Information provided by (Responsible Party):
Mikael Knip, Helsinki University
ClinicalTrials.gov Identifier:
NCT01735123
First received: November 24, 2012
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The proposed mechanistic formula feeding study sets out to identify the mechanism(s) by which an extensively hydrolyzed casein formula is able to protect children at risk for type 1 diabetes (T1D) from beta-cell autoimmunity.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Dietary Supplement: dietary intervention
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity: Potential Mechanisms

Resource links provided by NLM:


Further study details as provided by Helsinki University:

Primary Outcome Measures:
  • Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test Intestinal permeability at the age of 9 months assessed with the lactulose/mannitol test [ Time Frame: 3, 6, 9 and 12 months ] [ Designated as safety issue: No ]
    Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test


Secondary Outcome Measures:
  • Serum metabolic profile [ Time Frame: 3, 6, 9 and 12 months ] [ Designated as safety issue: Yes ]
    The serum metabolic profile wil be analyzed with metabolomics at the age of 3, 6, 9, and 12 months


Other Outcome Measures:
  • Intestinal microbiome [ Time Frame: 3, 6, 9 and 12 months ] [ Designated as safety issue: No ]
    The intestinal microbiome will be analyzed at the age of 3, 6, 9 , and 12 months


Estimated Enrollment: 120
Study Start Date: January 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: extensively hydrolyzed casein formula
The investigators plan to randomize 60 out of 120 infants to be weaned to an extensively hydrolyzed casein formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized.
Dietary Supplement: dietary intervention
hydrolyzed vs. nonhydrolyzed infant formula
Other Names:
  • An extensively hydrolyzed casein formula
  • A regular cow's milk based formula
Experimental: cow's milk based infant formula
The investigators plan to randomize 60 out of 120 infants to be weaned to a cow's milk based infant formula. Recruited mothers are encouraged to breast-feed. The dietary intervention will be applied until 9 months of age. The minimum exposure time to the study formula should be 90 days. Signs of beta-cell autoimmunity, i.e. diabetes-associated autoantibodies, will be monitored in the study participants, although the study will not have sufficient power to detect statistically significant differences in the seroconversion rate between the groups due to the limited number of infants randomized.
Dietary Supplement: dietary intervention
hydrolyzed vs. nonhydrolyzed infant formula
Other Names:
  • An extensively hydrolyzed casein formula
  • A regular cow's milk based formula

Detailed Description:

Based on clinical and experimental observations the study will focus on defining the effects of two different formulas on intestinal permeability, IL (interleukin)-17 immunity, serum metabolome, and gut microflora. The study will be based on a randomized pilot intervention trial using an intention to treat statistical analysis to compare e.g. gut permeability between the two treatment groups. The investigators hypothesize that the extensively hydrolyzed casein formula decreases intestinal permeability, down-regulates IL-17 immunity and proinflammatory lysophosphatidylcholines, and stabilize Lactobacilli levels in the gut microflora when compared to the conventional cow's milk formula. The study population comprises 120 newborn infants with HLA(Human Leukocyte Antigen)-conferred susceptibility to T1D. The mothers will be encouraged to exclusively breast-feed their infants as long as possible. The timing of weaning and introduction of study formula will be left to the mother. The infants are randomized to be weaned to one of two study formulas: ( i) standard cow's milk formula and (ii) an extensively hydrolyzed casein formula. The target will be that the infant should be exposed to his/her study formula for at least 90 days before the age of 270 days. The diet of the infant will be studied with 3-day food records at the age of 3, 6, 9, and 12 months of age. To estimate the amount of breast milk received the weight of the infant will be measured just before and after each lactation. The HLA genotype will be analyzed from cord blood, and the result will be available within 10 days after birth. The family will visit the Study Center when the infant is 3, 6, 9, and 12-month-old. Blood samples will be obtained on each visit. In addition the families are asked to collect stool samples at home once a month during the study. Intestinal permeability will be assessed with the lactulose/mannitol test at the age of 3, 6, 9, and 12 months. Gut microflora will be analyzed with high-throughput, culture-independent methods and serum metabolome with established metabolomics platforms. Il-17 immunity will be studied using peripheral blood mononuclear cells. This work will generate novel knowledge of the disease process leading to overt T1D by studying potential mechanism(s) mediating the protective effect conferred by an extensively hydrolyzed casein formula against beta-cell autoimmunity. The identification of such mechanism(s) will most likely facilitate the refinement of effective preventive measures based on modifications of early infant nutrition.

  Eligibility

Ages Eligible for Study:   up to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- The infant's parents give signed consent to participate and their HLA genotype is eligible.

Exclusion Criteria:

  • An older sibling of the newborn infant has been included in this study;
  • Multiple gestation;
  • The parents are unwilling or unable to feed the infant cow's milk based products for any reason (e.g., religious, cultural);
  • The gestational age of the newborn infant is less than 35 weeks
  • Inability of the family to take part in the study (e.g. the family had no access to the Study Center or telephone)
  • The newborn infant has a recognizable severe illness such as those due to chromosomal abnormality, congenital malformation, respiratory failure needing assisted ventilation, enzyme deficiencies, etc.;
  • The infant receives any infant formula other than study formula or Nutramigen at the delivery hospital
  • No HLA sample has been drawn before the age of 8 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735123

Contacts
Contact: Mikael Knip, M.D. +358 9 47172701 mikael.knip@helsinki.fi

Locations
Finland
Tampere University Hospital Recruiting
Tampere, Finland, 33521
Principal Investigator: Mikael Knip, M.D.         
Sponsors and Collaborators
Helsinki University
University of Turku
National Institute for Health and Welfare, Finland
Tampere University Hospital
Investigators
Principal Investigator: Mikael Knip, M.D. Helsinki University
  More Information

No publications provided

Responsible Party: Mikael Knip, Professor, Helsinki University
ClinicalTrials.gov Identifier: NCT01735123     History of Changes
Other Study ID Numbers: 1DP3DK094338-01
Study First Received: November 24, 2012
Last Updated: March 3, 2014
Health Authority: Finland: Ethics Committee

Keywords provided by Helsinki University:
infant formula
diet
diabetes mellitus, type 1
autoimmunity

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Caseins
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014