NCT01735123

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
87

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jan 2013

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 24, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 28, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

January 1, 2013

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

February 27, 2017

Status Verified

February 1, 2017

Enrollment Period

3.5 years

First QC Date

November 24, 2012

Last Update Submit

February 24, 2017

Conditions

Diabetes Mellitus, Type 1

Keywords

infant formuladietdiabetes mellitus, type 1autoimmunity

Outcome Measures

Primary Outcomes (1)

  • 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

    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 Outcomes (1)

  • Serum metabolic profile

    3, 6, 9 and 12 months

Other Outcomes (1)

  • Intestinal microbiome

    3, 6, 9 and 12 months

Study Arms (2)

extensively hydrolyzed casein formula

EXPERIMENTAL

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

cow's milk based infant formula

EXPERIMENTAL

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

Interventions

dietary interventionDIETARY_SUPPLEMENT

hydrolyzed vs. nonhydrolyzed infant formula

Also known as: An extensively hydrolyzed casein formula, A regular cow's milk based formula
cow's milk based infant formulaextensively hydrolyzed casein formula

Eligibility Criteria

AgeUp to 12 Months
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Tampere University Hospital

Tampere, 33521, Finland

Location

Related Publications (4)

  • Lalli MK, Salo TE, Hakola L, Knip M, Virtanen SM, Vatanen T. Associations between dietary fibers and gut microbiome composition in the EDIA longitudinal infant cohort. Am J Clin Nutr. 2025 Jan;121(1):83-99. doi: 10.1016/j.ajcnut.2024.11.011. Epub 2024 Nov 16.

    PMID: 39551356DERIVED

  • Koivusaari K, Niinisto S, Nevalainen J, Honkanen J, Ruohtula T, Koreasalo M, Ahonen S, Akerlund M, Tapanainen H, Siljander H, Miettinen ME, Alatossava T, Ilonen J, Vaarala O, Knip M, Virtanen SM. Infant Feeding, Gut Permeability, and Gut Inflammation Markers. J Pediatr Gastroenterol Nutr. 2023 Jun 1;76(6):822-829. doi: 10.1097/MPG.0000000000003756. Epub 2023 Mar 12.

    PMID: 36913717DERIVED

  • Lamichhane S, Siljander H, Salonen M, Ruohtula T, Virtanen SM, Ilonen J, Hyotylainen T, Knip M, Oresic M. Impact of Extensively Hydrolyzed Infant Formula on Circulating Lipids During Early Life. Front Nutr. 2022 May 24;9:859627. doi: 10.3389/fnut.2022.859627. eCollection 2022.

    PMID: 35685890DERIVED

  • Siljander H, Jason E, Ruohtula T, Selvenius J, Koivusaari K, Salonen M, Ahonen S, Honkanen J, Ilonen J, Vaarala O, Virtanen SM, Lahdeaho ML, Knip M. Effect of Early Feeding on Intestinal Permeability and Inflammation Markers in Infants with Genetic Susceptibility to Type 1 Diabetes: A Randomized Clinical Trial. J Pediatr. 2021 Nov;238:305-311.e3. doi: 10.1016/j.jpeds.2021.07.042. Epub 2021 Jul 20.

    PMID: 34293372DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Autoimmune Diseases

Interventions

Diet Therapy

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Nutrition TherapyTherapeutics

Study Officials

  • Mikael Knip, M.D.

    University of Helsinki

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

November 24, 2012

First Posted

November 28, 2012

Study Start

January 1, 2013

Primary Completion

July 1, 2016

Study Completion

August 1, 2016

Last Updated

February 27, 2017

Record last verified: 2017-02

Locations

FI(1)