Nutritional Intervention to Prevent Diabetes (TN06)

April 27, 2020 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Type 1 Diabetes (T1D) is an autoimmune disease. This means that the immune system (the part of the body which helps fight infections) mistakenly attacks and destroys the cells that produce insulin (islet cells found in the pancreas). As these cells are destroyed, the body's ability to produce insulin decreases.

The autoimmune process is thought to be initiated by a gene-environment interaction. The genetics involved in the development of T1D are fairly well understood. There is a higher risk of developing T1D with the presence of the human leukocyte antigen (HLA) DR3 or DR4. It is also known that not everyone with these genes actually develops T1D. Therefore, one or more environmental factors are thought to contribute to the process of developing T1D.

The consumption of the anti-inflammatory fatty acids, the omega-3 fatty acids, has decreased significantly in the past 100 years. At the same time a rise in the incidence of T1D, especially in young children has occurred. Because of the warnings to eliminate fish during pregnancy, pregnant women are consuming even less omega-3 fatty acids during fetal development.

Observations have been made that children who have received omega-3 fatty acid supplementation have a lower risk of T1D. Omega-3 fatty acids could have a protective effect that may occur during pregnancy, infancy, or both. The mechanism of this protection may be due to the DHA mediated suppression of the inflammatory response.

Patients at higher risk for T1D have an increased pro-inflammatory environment. We hypothesize that DHA supplementation during pregnancy and early childhood will block the initial pro-inflammatory events and prevent development of islet cell autoimmunity in children at higher risk for T1D.

This study is a feasibility study to determine if a full-scale DHA supplementation study will be implemented. If a full study is implemented, the primary outcome will be to determine if nutritional supplementation with omega-3 fatty acids during the last trimester of a mother's pregnancy and/or the first three years of life for children who are at higher risk of T1D will prevent the development of islet autoimmunity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There are two possible entry pathways for study participants. The first pathway is the entry point for pregnant mothers in their third trimester (24 weeks gestational age) whose babies may be at higher risk for T1D based on family history. At birth, or soon after, their babies will be tested for HLA type (to look for the specific gene which confers a higher risk of developing T1D). If the HLA typing shows that the baby is at higher risk for T1D and no protective genes are present, the baby will then continue in the study. The second pathway is the entry point for babies whose mothers were not enrolled during pregnancy. These babies will also be tested for HLA type. Their eligibility will be based on the presence of higher risk genes or the presence of a multiplex family history. This screening process may take place up until the baby is 5 months old.

Eligible participants (pregnant women or infants) will be randomized to one of the two study groups: DHA (docosahexaenoic acid) study substance (this is the intervention) or control study substance (this is the placebo). The DHA (docosahexaenoic acid) to be used in this trial is produced from algae, not from fish oil, so there is no risk of mercury or pesticide contamination.

Pregnant and nursing mothers who are assigned to the control group will receive study capsules containing a vegetable oil and no DHA (docosahexaenoic acid) . Pregnant and nursing mothers who are assigned to the experimental group will receive study capsules containing DHA (docosahexaenoic acid) . During pregnancy and while breastfeeding, infants will receive the study substance indirectly through their mother (either the placenta or breastmilk).

Infants who are either partially or exclusively formula feeding will receive study substance more directly through the study formula. The control group will receive study formula containing the typical amount of DHA that can be found in some infant formulas, while infants in the experimental group will receive study formula containing a larger amount of DHA (docosahexaenoic acid) than typically found in some infant formulas. By six to twelve months of age, all infants will get study supplement added to solid foods.

All mothers will have contact with the study site every 3 months. Nursing mothers will provide samples of breast milk for fatty acids analysis at these visits.

Infants will need to come to follow-up study visits every 6 months. At each of these visits, the infant will have a limited physical exam and blood drawn from a vein to monitor immune activity, levels of fatty acid and vitamin D, and to check for diabetes-related autoantibodies. Infants/children cannot continue in the study if they: (1) develop two positive autoantibodies, present at two consecutive visits, or (2) develop T1D.

All follow-up study visits will continue for 1-2 years, and possibly an additional 2 years if a full-scale study is initiated.

Study Type

Interventional

Enrollment (Actual)

99

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

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital of Los Angeles
      • Orange, California, United States, 92868-3835
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University-Riley Hospital for Children
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Health Care
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Missouri
      • Kansas City, Missouri, United States, 64108-9898
        • The Children's Mercy Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Utah Diabetes Center

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 5 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Pregnant mothers are eligible for enrollment into this study if they:

  1. Have T1D or the child's father, or a full or half-sibling of the child has T1D
  2. Are 18 years of age or older
  3. Are in their third trimester of pregnancy (i.e. gestation is 24 weeks or longer)
  4. Have understood and signed a written informed consent and HIPAA authorization
  5. Are willing to undergo randomization to ensure that equal numbers receive the DHA study substance versus the control

Infants are eligible for enrollment into this study if they:

  1. Are less than or equal to six months of age on the date of randomization

  2. Are found to be at risk for type 1 diabetes because they have a mother, father or full or half-sibling with T1D AND

    • have a DR3 or DR4 allele OR
    • have another relative (includes both 1st and 2nd degree relatives) with T1D (multiplex family)
  3. Have a parent or legal guardian who has understood and signed a written informed consent and HIPAA authorization
  4. Have a parent(s) or legal guardian(s) who are willing for their baby to undergo randomization to ensure that equal numbers receive the DHA study substance versus the control

Exclusion Criteria

Pregnant mothers are NOT eligible for enrollment into this study if they:

  1. Have any condition the investigator believes will put the mother or her fetus at an unacceptable medical risk for participation in this study
  2. Have a known complication of pregnancy causing an increased risk for the mother or fetus prior to entry into the study
  3. Have previously had multiple (2 or more) pre-term births (<36 weeks)
  4. Are diabetic and have a known HbA1c greater than 9% at anytime during the pregnancy (however, healthy infants after birth may qualify in spite of the above restrictions during pregnancy)
  5. Plan to take DHA supplementation during the study

Infants are NOT eligible for enrollment into this study if they:

  1. Have any condition the investigator believes will put the subject at an unacceptable medical risk for participation in this study
  2. Have a mother with a condition the investigator believes will put her at an unacceptable medical risk for participation in this study
  3. Have a nursing mother who plans to take DHA supplementation or has a parent or legal guardian who plans to provide supplementation to his/her infant independently during the study
  4. Have a protective allele (DQB1*0602 or DRB1*0403)
  5. Were born prior to 36 weeks gestation and require a pre-term infant formula

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: DHA Treatment Group
DHA study treatment given on daily basis to nursing mother (breast milk) or baby as either formula, or capsules (removing content and mixing with food)depending on age of child.
Dietary supplement: DHA Treatment
DHA study treatment given on daily basis to nursing mother (breast milk) or baby as either formula, or capsules (removing content and mixing with food) depending on age of child.
Placebo Comparator: Control Group
Placebo for DHA given to nursing mother (breast milk), study formula, or capsules (removing content and mixing with food)depending on age of child.
Dietary supplement: Placebo for DHA
Study placebo given on daily basis to nursing mother (breast milk) or baby as either formula, or capsules (removing content and mixing with food)depending on age of child.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
20% higher level of plasma and/or red blood cell membrane phospholipid DHA achieved in the treatment group
Time Frame: Every 3 months for two years; every 6 months until age 3.
Every 3 months for two years; every 6 months until age 3.
At least a 20% reduction in the level of the major inflammatory cytokine, IL1-beta, achieved in the plasma of the treatment group
Time Frame: Every 3 months for two years; every 6 months until age 3.
Every 3 months for two years; every 6 months until age 3.

Secondary Outcome Measures

Outcome Measure
Time Frame
95% of families will continue to attend follow-up visits
Time Frame: Every 3 months for two years; every 6 months until age 3.
Every 3 months for two years; every 6 months until age 3.

Collaborators and Investigators

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

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Study Chair: Jay S Skyler, M.D., University of Miami
  • Principal Investigator: H. Peter Chase, MD, The University of Colorado Health Science Center- Barbara Davis Center for Childhood Diabetes
  • Principal Investigator: Michael Clare-Salzler, MD, University of Florida, Department of Pathology, Department of Pediatrics, Diabetes Research Program

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

Helpful Links

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 (Actual)

June 1, 2006

Primary Completion (Actual)

February 1, 2008

Study Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

June 2, 2006

First Submitted That Met QC Criteria

June 2, 2006

First Posted (Estimate)

June 5, 2006

Study Record Updates

Last Update Posted (Actual)

April 29, 2020

Last Update Submitted That Met QC Criteria

April 27, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TN06 NIP
  • UC4DK097835 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn06-nip-pilot/?query=tn06

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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