Nutritional Intervention to Prevent Diabetes

NCT00333554 | Completed DMC

• 2 other identifiers: TN06 NIPUC4DK097835
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

DHA; docosahexaenoic acid; omega-3 fatty acid; fish oil; pregnancy; infancy; prevention; "at risk" for developing type 1 diabetes; juvenile diabetes; T1D; diabetes mellitus; Type 1 diabetes TrialNet; TrialNet; dietary supplementation; nutrition

Outcome Measures

Primary Outcomes (2)

• 20% higher level of plasma and/or red blood cell membrane phospholipid DHA achieved in the treatment group

  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

  Every 3 months for two years; every 6 months until age 3.

Secondary Outcomes (1)

• 95% of families will continue to attend follow-up visits

  Every 3 months for two years; every 6 months until age 3.

Study Arms (2)

DHA Treatment Group

EXPERIMENTAL

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

Control Group

PLACEBO COMPARATOR

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

Interventions

DHA Treatment DIETARY_SUPPLEMENT

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.

DHA Treatment Group

Placebo for DHA DIETARY_SUPPLEMENT

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.

Control Group

Eligibility Criteria

• Age: Up to 5 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Pregnant mothers are eligible for enrollment into this study if they:
• Have T1D or the child's father, or a full or half-sibling of the child has T1D
• Are 18 years of age or older
• Are in their third trimester of pregnancy (i.e. gestation is 24 weeks or longer)
• Have understood and signed a written informed consent and HIPAA authorization
• 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:
• Are less than or equal to six months of age on the date of randomization
• 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)
• Have a parent or legal guardian who has understood and signed a written informed consent and HIPAA authorization
• 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

You may not qualify if:

• Pregnant mothers are NOT eligible for enrollment into this study if they:
• Have any condition the investigator believes will put the mother or her fetus at an unacceptable medical risk for participation in this study
• Have a known complication of pregnancy causing an increased risk for the mother or fetus prior to entry into the study
• Have previously had multiple (2 or more) pre-term births (\<36 weeks)
• 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)
• Plan to take DHA supplementation during the study
• Infants are NOT eligible for enrollment into this study if they:
• Have any condition the investigator believes will put the subject at an unacceptable medical risk for participation in this study
• Have a mother with a condition the investigator believes will put her at an unacceptable medical risk for participation in this study
• 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
• Have a protective allele (DQB1\*0602 or DRB1\*0403)
• Were born prior to 36 weeks gestation and require a pre-term infant formula

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (9)

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868-3835, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Indiana University-Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108-9898, United States

Location

Utah Diabetes Center

Salt Lake City, Utah, 84108, United States

Location

Related Publications (9)

• Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, Chase HP, Eisenbarth GS. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996 Jul;45(7):926-33. doi: 10.2337/diab.45.7.926.

  PMID: 8666144 BACKGROUND

• Karvonen M, Pitkaniemi J, Tuomilehto J. The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group. Diabetes Care. 1999 Jul;22(7):1066-70. doi: 10.2337/diacare.22.7.1066.

  PMID: 10388969 BACKGROUND

• Rice R. Fish and healthy pregnancy: more than just a red herring! Prof Care Mother Child. 1996;6(6):171-3.

  PMID: 9077255 BACKGROUND

• Stene LC, Joner G; Norwegian Childhood Diabetes Study Group. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003 Dec;78(6):1128-34. doi: 10.1093/ajcn/78.6.1128.

  PMID: 14668274 BACKGROUND

• Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989 Feb 2;320(5):265-71. doi: 10.1056/NEJM198902023200501.

  PMID: 2783477 BACKGROUND

• Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999 Sep;70(3 Suppl):560S-569S. doi: 10.1093/ajcn/70.3.560s.

  PMID: 10479232 BACKGROUND

• Chase HP, Cooper S, Osberg I, Stene LC, Barriga K, Norris J, Eisenbarth GS, Rewers M. Elevated C-reactive protein levels in the development of type 1 diabetes. Diabetes. 2004 Oct;53(10):2569-73. doi: 10.2337/diabetes.53.10.2569.

  PMID: 15448085 BACKGROUND

• Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE. Fish oil and glycemic control in diabetes. A meta-analysis. Diabetes Care. 1998 Apr;21(4):494-500. doi: 10.2337/diacare.21.4.494.

  PMID: 9571330 BACKGROUND

• Chase HP, Boulware D, Rodriguez H, Donaldson D, Chritton S, Rafkin-Mervis L, Krischer J, Skyler JS, Clare-Salzler M; Type 1 Diabetes TrialNet Nutritional Intervention to Prevent (NIP) Type 1 Diabetes Study Group. Effect of docosahexaenoic acid supplementation on inflammatory cytokine levels in infants at high genetic risk for type 1 diabetes. Pediatr Diabetes. 2015 Jun;16(4):271-9. doi: 10.1111/pedi.12170. Epub 2014 Jul 12.

  PMID: 25039804 RESULT

Related Links

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MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jay S Skyler, M.D.

  University of Miami

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2006
• First Posted: June 5, 2006
• Study Start: June 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: April 1, 2013
• Last Updated: April 29, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (9)