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

February 24, 2017 updated by: Mikael Knip, University of Helsinki

Early Dietary Intervention and Later Signs of Beta-Cell Autoimmunity: Potential Mechanisms

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Tampere, Finland, 33521
        • Tampere University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 year (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Intestinal permeability will be determined at the age of 3, 6, 9 and 12 months with the lactulose/mannitol test
3, 6, 9 and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum metabolic profile
Time Frame: 3, 6, 9 and 12 months
The serum metabolic profile wil be analyzed with metabolomics at the age of 3, 6, 9, and 12 months
3, 6, 9 and 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intestinal microbiome
Time Frame: 3, 6, 9 and 12 months
The intestinal microbiome will be analyzed at the age of 3, 6, 9 , and 12 months
3, 6, 9 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Helsinki

Collaborators

University of Turku
Tampere University Hospital
Finnish Institute for Health and Welfare

Investigators

  • Principal Investigator: Mikael Knip, M.D., University of Helsinki

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

November 24, 2012

First Submitted That Met QC Criteria

November 24, 2012

First Posted (Estimate)

November 28, 2012

Study Record Updates

Last Update Posted (Actual)

February 27, 2017

Last Update Submitted That Met QC Criteria

February 24, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1DP3DK094338-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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