Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies

NCT04069195 | Unknown

• 1 other identifier: WRNMMC-2018-0126
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: Determine the effects of maternal docosahexaenoic acid (DHA) supplementation during pregnancy on levels of DHA, synaptamide (novel anti-inflammatory metabolite), and inflammatory biomarkers during pregnancy and at delivery Research Design: Double blind randomized placebo-controlled study of maternal DHA supplementation during pregnancy. Methodology /Technical Approach: Investigators plan to enroll 100 pregnant women with a high risk pregnancy related to (1) a pre-pregnancy Body Mass Index (BMI) of ≥30.0 kg/m2 and/or (2) a history of prior preterm delivery at ≤35+6 weeks gestation. Women will be enrolled between the 8th and 14th week of pregnancy and randomized to receive a once daily DHA supplement (DSM Nutritional Products, Columbia Maryland, DHA capsule 441mg/cap) or a placebo (DSM Nutritional Products, Columbia Maryland, Corn Oil/Soybean oil 50/50 mix) for the duration of the pregnancy. DHA is an omega-3 long chain polyunsaturated fatty acid (LCPUFA) and placebo composed of omega-6 LCPUFA's. Investigators will measure maternal levels of plasma DHA, Synaptamide and inflammatory biomarkers at enrollment, at 26-30 weeks of pregnancy, and from cord blood at delivery. Sociodemographic and clinical characteristics will be collected for each mother from pregnancy onset until discharge following delivery. The infant health record and parental report will be reviewed to record clinical data from birth to 12 months corrected age for short term health outcomes potentially related to inflammation-related morbidities, including growth and development, acute infection requiring hospital admission, and any allergic disorder. All plasma samples will be processed at Dr. Kim's NIAAA/NIH laboratories using high-performance liquid chromatography with tandem mass spectrometry

Conditions

Inflammation; Pregnancy Related

Keywords

Inflammation; DHA; Pregnancy; preterm; overweight

Outcome Measures

Primary Outcomes (9)

• Measure DHA

  Measurement of maternal plasma DHA using tandem mass spec

  Sample obtained between 8-14 weeks of pregnancy

• Measure DHA

  Measurement of maternal plasma DHA using tandem mass spec

  Sample obtained between 26-30 weeks of pregnancy

• Measure DHA

  Measurement of fetal plasma DHA using tandem mass spec

  Sample obtained from cord blood at time of infant delivery

• Measure synaptamide

  Measurement of maternal plasma synaptamide using tandem mass spec

  Sample obtained between 8-14 weeks of pregnancy

• Measure synaptamide

  Measurement of maternal plasma synaptamide using tandem mass spec

  Sample obtained between 26-30 weeks of pregnancy

• Measure synaptamide

  Measurement of fetal plasma synaptamide using tandem mass spec

  Sample obtained from cord blood at time of infant delivery

• Measure inflammatory biomarkers

  Measurement of plasma cytokine levels using ELISA human cytokine panel

  Sample obtained between 8-14 weeks of pregnancy

• Measure inflammatory biomarkers

  Measurement of plasma cytokine levels using ELISA human cytokine panel

  Sample obtained between 26-30 weeks of pregnancy

• Measure inflammatory biomarkers

  Measurement of plasma cytokine levels using ELISA human cytokine panel

  Sample obtained from cord blood at time of infant delivery

Secondary Outcomes (42)

• Maternal Gestational weight gain at end of pregnancy in placebo vs. DHA supplement groups

  At time of infant delivery

• Infant delivery method

  At time of infant delivery

• Delivery complications

  at time of infant delivery

• Maternal death

  From enrollment in study at 8-14 weeks of pregnancy until 6 months after infant delivery

• Pre-eclampsia

  From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first

Study Arms (2)

DHA supplement

ACTIVE COMPARATOR

Patients in the intervention group will recieve a \~1000mg capsule containing \~400mg of DHA. This is not standard of care and is being done for research purposes only. Patients will take this capsule once daily begining between 8-14 weeks of pregnancy until delivery of their infant.

Dietary Supplement: DHA supplement

corn oil: Soybean oil placebo

PLACEBO COMPARATOR

Patients in the Placebo group will recieve a \~1000mg capusle containing no DHA and filled with 50:50 mix of corn and soybean oils. This oil is ubiquitous in the american diet and only a very small amount of additional oil will be ingested for study purposes. Giving pregnant women this oil is not standard of care and is being done for research purposes only. Patients will continue taking this placebo from enrollment at 8-14 weeks of pregnancy until time of delivery.

Dietary Supplement: Corn Oil: Soybean Oil

Interventions

DHA supplement DIETARY_SUPPLEMENT

Patient's will be randomized to recieve either DHA or 50:50 corn oil/soybean oil supplement as a once daily supplement to be taken from enrollment through delivery of their infant

Also known as: Docosahexaenoic Acid

DHA supplement

Corn Oil: Soybean Oil DIETARY_SUPPLEMENT

Patient's will be randomized to recieve either DHA or 50:50 corn oil/soybean oil supplement as a once daily supplement to be taken from enrollment through

corn oil: Soybean oil placebo

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Enrolling only pregnant women and their offspring
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• regnant female military health care beneficiaries ≥18 years of age
• Between the 8th and 14th week of pregnancy at enrollment
• BMI of ≥30.0 kg/m2 and/or history of previous preterm delivery at \<36 weeks gestation
• Planning to deliver at WRNMMC
• DEERS-eligible

You may not qualify if:

• Routine use of DHA supplement (including DHA containing prenatal vitamins) and/or fish consumption greater than twice per week
• Women with a fish allergy
• Known major fetal anomaly believed to be lethal
• Maternal treatment for clotting disorder
• Allergy to corn or soybean oils

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead
• National Institutes of Health (NIH): collaborator
• DSM Nutritional Products, Inc.: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Walter Reed National Miltiary medical center

Bethesda, Maryland, 20889, United States

RECRUITING

Related Publications (11)

• Valentine CJ. Maternal dietary DHA supplementation to improve inflammatory outcomes in the preterm infant. Adv Nutr. 2012 May 1;3(3):370-6. doi: 10.3945/an.111.001248.

  PMID: 22585914 BACKGROUND

• Martin CR, Dasilva DA, Cluette-Brown JE, Dimonda C, Hamill A, Bhutta AQ, Coronel E, Wilschanski M, Stephens AJ, Driscoll DF, Bistrian BR, Ware JH, Zaman MM, Freedman SD. Decreased postnatal docosahexaenoic and arachidonic acid blood levels in premature infants are associated with neonatal morbidities. J Pediatr. 2011 Nov;159(5):743-749.e1-2. doi: 10.1016/j.jpeds.2011.04.039. Epub 2011 Jun 12.

  PMID: 21658712 BACKGROUND

• Ma L, Li N, Liu X, Shaw L, Li Calzi S, Grant MB, Neu J. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice. Nutrition. 2012 Nov-Dec;28(11-12):1186-91. doi: 10.1016/j.nut.2012.04.001.

  PMID: 23044165 BACKGROUND

• Hofer N, Kothari R, Morris N, Muller W, Resch B. The fetal inflammatory response syndrome is a risk factor for morbidity in preterm neonates. Am J Obstet Gynecol. 2013 Dec;209(6):542.e1-542.e11. doi: 10.1016/j.ajog.2013.08.030. Epub 2013 Aug 29.

  PMID: 23994220 BACKGROUND

• De Dooy JJ, Mahieu LM, Van Bever HP. The role of inflammation in the development of chronic lung disease in neonates. Eur J Pediatr. 2001 Aug;160(8):457-63. doi: 10.1007/s004310100785.

  PMID: 11548181 BACKGROUND

• Cheng SB, Sharma S. Interleukin-10: a pleiotropic regulator in pregnancy. Am J Reprod Immunol. 2015 Jun;73(6):487-500. doi: 10.1111/aji.12329. Epub 2014 Oct 1.

  PMID: 25269386 BACKGROUND

• Kim HY, Spector AA. Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function. Prostaglandins Leukot Essent Fatty Acids. 2013 Jan;88(1):121-5. doi: 10.1016/j.plefa.2012.08.002. Epub 2012 Sep 5.

  PMID: 22959887 BACKGROUND

• Meijerink J, Poland M, Balvers MG, Plastina P, Lute C, Dwarkasing J, van Norren K, Witkamp RF. Inhibition of COX-2-mediated eicosanoid production plays a major role in the anti-inflammatory effects of the endocannabinoid N-docosahexaenoylethanolamine (DHEA) in macrophages. Br J Pharmacol. 2015 Jan;172(1):24-37. doi: 10.1111/bph.12747. Epub 2014 Sep 23.

  PMID: 24780080 BACKGROUND

• Balvers MG, Verhoeckx KC, Plastina P, Wortelboer HM, Meijerink J, Witkamp RF. Docosahexaenoic acid and eicosapentaenoic acid are converted by 3T3-L1 adipocytes to N-acyl ethanolamines with anti-inflammatory properties. Biochim Biophys Acta. 2010 Oct;1801(10):1107-14. doi: 10.1016/j.bbalip.2010.06.006. Epub 2010 Jun 27.

  PMID: 20601112 BACKGROUND

• Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P; DOMInO Investigative Team. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA. 2010 Oct 20;304(15):1675-83. doi: 10.1001/jama.2010.1507.

  PMID: 20959577 BACKGROUND

• Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008 Jan;93(1):F45-50. doi: 10.1136/adc.2006.099085. Epub 2006 Dec 21.

  PMID: 17185423 BACKGROUND

MeSH Terms

Conditions

Inflammation; Premature Birth; Overweight

Interventions

Docosahexaenoic Acids

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• Peter F Knickerbocker, DO

  Walter Reed National Miltary Medical Center

  PRINCIPAL INVESTIGATOR

• Kim Hee-Yong, PhD

  NIH/ NIAAA

  STUDY DIRECTOR

• Carl Hunt, MD

  Uniformed Services University of the Health Sciences

  STUDY CHAIR

Central Study Contacts

Peter F Knickerbocker, DO

CONTACT

215-298-2476; peteknickerbocker@gmail.com

Carl Hunt, MD

CONTACT

3017675514; carl.hunt@usuhs.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded, randomized, placebo controlled
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Double Blinded, Randomized, Placebo controlled

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: August 28, 2019
• Study Start: February 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)