InflammationNCT04069195
Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
A study testing DHA supplement and Corn Oil: Soybean Oil in people with Inflammation and Pregnancy Related, run by Walter Reed National Military Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammation, Pregnancy Related
- What is being tested?
- DHA supplement and Corn Oil: Soybean Oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2019to 1 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- All infants born to mothers enrolled in this study who do not meet any exclusion criteria
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Walter Reed National Miltiary medical center
Bethesda, Maryland, 20889
Peter F Knickerbocker, DO, 215-298-2476, peteknickerbocker@gmail.com
Carl Hunt, MD, 3017675514, carl.hunt@usuhs.edu
About this study
Official title: Placebo Controlled Trial of Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
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
Read the detailed description
All pregnant women meeting the inclusion/exclusion criteria will be identified at the time of their regular OB appointments between the 8th and the 14th week of pregnancy (+/- 3 days) Research team members will approach potential subjects to explain the study and obtain consent for their participation Patients who give their consent for enrollment will be asked to complete a dietary survey at the time of enrollment Patients will be given a paper script for study drug to be taken to the Walter Reed Military Medical Center pharmacy to obtain study drug The Investigational Pharmacy will randomize the patients in double blinded fashion to the intervention group or placebo group.
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 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 The placebo and intervention drugs will be packaged in the same capsule membrane and will be indistinguishable by color, shape, or taste.
Patients will be instructed to take 1 capule PO daily until their child is delivered Patients will be issued a 3 month supply of study drug at enrollment and will get refills from the investigational pharmacy
≤5ml of whole blood will be obtained from each subject at enrollment and at 26-30 weeks gestation (+/- 3 days), as part of a routine blood sampling. It is standard of care to collect blood at this point in pregnancy for lab evaluation. The additional tube of blood collected for this study is for research purposes only and not part of the standard of care. This sample will be centrifuged, and the separated plasma will be labeled and frozen at -80° C pending transport to Dr. Kim's lab at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for bulk analyses.
At delivery, ≤5ml of umbilical cord blood will be obtained from an umbilical artery and from the umbilical vein. These samples will be processed and stored in a similar fashion as the earlier samples. Cord blood is a medical waste product, and collection will therefore have no adverse effect for either mother or newborn. It is standard of care to collect cord blood by OB request for lab evaluation. Collecting additional cord blood for this study anaylsis is for research purposes only All enrollees will complete a dietary survey upon enrollment at 8-14 weeks (+/- 3 days), at 26-30th week of pregnancy (+/- 3 days), and during the delivery admission. This survey will also include the subject's self-report on compliance with taking the study supplement All plasma samples collected will be processed at Dr. Kim's National Institute on Alcohol Abuse and Alcoholism/ National Insititute of Health (NIAAA/NIH) laboratories The Cytokine Assays for IL-6, Il-10, TNF- alpha will be run in Dr Kim's lab using Ensyme Linked Immunosorbent Assay (ELISA) testing The DHA and Synaptamide levels will be analyzed in Dr. Kim's lab using High performance liquid chromatrography with tandem mass spectrometry All babies from multiple birth pregnancies will be enrolled in this study The offspring of enrolled women will be followed through 12 months corrected age to assess the longer term outcomes of study intervention Information will be collected from the maternal medical record at time of enrollment, infant delivery and postpartum discharge.
Information will be collected from the infant medical record at time of birth discharge, and 12 months corrected age.
- Conditions
- Inflammation, Pregnancy Related
- Being tested
- DHA supplement, Corn Oil: Soybean Oil
- Keywords
- Inflammation, DHA, Pregnancy, preterm, overweight
- Medical subject headings
- Inflammation, Premature Birth, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHA supplementDietary supplement
Also called Docosahexaenoic Acid
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
Corn Oil: Soybean OilDietary 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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Corn Oil: Soybean Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure DHA
Measurement of maternal plasma DHA using tandem mass spec
Measured: Sample obtained between 8-14 weeks of pregnancy
Measure DHA
Measurement of maternal plasma DHA using tandem mass spec
Measured: Sample obtained between 26-30 weeks of pregnancy
Measure DHA
Measurement of fetal plasma DHA using tandem mass spec
Measured: Sample obtained from cord blood at time of infant delivery
Measure synaptamide
Measurement of maternal plasma synaptamide using tandem mass spec
Measured: Sample obtained between 8-14 weeks of pregnancy
Measure synaptamide
Measurement of maternal plasma synaptamide using tandem mass spec
Measured: Sample obtained between 26-30 weeks of pregnancy
Measure synaptamide
Measurement of fetal plasma synaptamide using tandem mass spec
Measured: Sample obtained from cord blood at time of infant delivery
Measure inflammatory biomarkers
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measured: Sample obtained between 8-14 weeks of pregnancy
Measure inflammatory biomarkers
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measured: Sample obtained between 26-30 weeks of pregnancy
Measure inflammatory biomarkers
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measured: 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
Compare maternal gestational weight gain at the end of pregnancy between intervention and placebo groups
Measured: At time of infant delivery
Infant delivery method
Compare delivery method used to delivery infant between intervention and placebo groups
Measured: At time of infant delivery
Delivery complications
Compare any documented delivery complications between intervention and placebo groups
Measured: at time of infant delivery
Maternal death
Number of maternal deaths in intervention group vs placebo group
Measured: From enrollment in study at 8-14 weeks of pregnancy until 6 months after infant delivery
Pre-eclampsia
Presence or absence of pre-eclampsia in intervention vs placebo groups
Measured: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
chorioamionitis
Presence or absence of chorioamionitis in intervention vs placebo groups
Measured: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
Gestational Diabetes Melitus
Presence or absence of Gestational Diabetes Mellitus in intervention vs placebo groups
Measured: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
non-gestational Diabetes mellitus
Presence or absence of non-Gestational Diabetes Mellitus in intervention vs placebo groups
Measured: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
Preterm Premature Rupture of Membranes
Presence or absence of Preterm Premature Rupture of Membranes in intervention vs placebo groups
Measured: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
going past due dates
Presence or absence of going past due dates in intervention vs placebo groups
Measured: during last month of pregnancy
Placental pathology
Any placental pathology documented on maternal delivery summary in intervention vs. placebo groups
Measured: at time of delivery
Head circumference at birth
Measurement of head circumference at birth in placebo vs. Intervention
Measured: At time of infant birth
Length at birth
Measurement of length at birth in placebo vs. Intervention
Measured: At time of infant birth
weight at birth
Measurement of weight at birth in placebo vs. Intervention
Measured: At time of infant birth
Gestational age at birth
Gestational age at infant birth in both placebo and intervention groups
Measured: At time of infant birth
APGAR score at 1 min
APGAR score assessed for infants in both placebo and intervention groups
Measured: At time of infant birth
APGAR score at 5 min
APGAR score assessed for infants in both placebo and intervention groups
Measured: At time of infant birth
Resuscitation beyond warm/dry stimulate at birth
Presence or absence of any resuscitation beyond warm, dry and stimulate at infant birth
Measured: At time of infant birth
Presence or absence or requirement for respiratory assistance within the first 24 hours after birth
Presence or absence of any respiratory support outside of the delivery room in first 24 hours of birth placebo vs intervention groups
Measured: From NICU admission to 24 hours after birth
Days of antibiotic exposure during birth hospitalization
Number of 24hr periods in which infant was exposed to antibiotics during birth hospitalization
Measured: During birth admission up to 8 months of chronologic age or discharge from hospital whichever happens sooner
NICU admission
Presence or absence of NICU admission in placebo vs intervention groups
Measured: Within the first 5 days of infant's life
Duration of birth admission
Number of 24hr periods patient was present in hospital during birth admission
Measured: Birth through 12 months of age or infant discharge, whichever occurs sooner
Requirement for phototherapy during birth admission
Presence or absence of phototherapy during birth admission in placebo vs intervention groups
Measured: Birth through 14 days of infant life
Culture proven sepsis
Presence or absence of culture proven sepsis during birth admission in placebo vs intervention groups
Measured: From birth through 12 months or until infant discharge whichever occurs sooner
Infant Death
Number of infants that died during birth hospitalization in both the placebo and intervention groups
Measured: From birth through 12 months or until infant discharge whichever occurs sooner
Weight at infant hospital discharge
Weight at infant hospital discharge in placebo vs intervention group
Measured: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
head circumference at infant hospital discharge
head circumference at infant hospital discharge in placebo vs intervention group
Measured: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
Length at infant hospital discharge
Length at infant hospital discharge in placebo vs intervention group
Measured: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
Feeding plan at infant discharge
Feeding plan documented as exclusive breastfeeding, formula and breastfeeding or exclusive formula feeding
Measured: At 12 months chronological if still admitted or at infant discharge, whichever occurs sooner
Infant diagnosis in medical record
Compare infant diagnosis recorded in medical record in placebo vs intervention group
Measured: at 12 months corrected
infant weight at 6 months corrected age
Weight at 6 months corrected age documented in medical record in placebo vs intervention group
Measured: at 6 months corrected
infant weight at 12 months corrected age
Weight at 12 months corrected age documented in medical record in placebo vs intervention group
Measured: at 12 months corrected
head circumferene weight at 6 months corrected age
head circumferene at 6 months corrected age documented in medical record in placebo vs intervention group
Measured: at 6 months corrected
head circumference weight at 12 months corrected age
head circumference at 12 months corrected age documented in medical record in placebo vs intervention group
Measured: at 12 months corrected
Length weight at 6 months corrected age
Length at 6 months corrected age documented in medical record in placebo vs intervention group
Measured: at 6 months corrected
Length weight at 12 months corrected age
Length at 12 months corrected age documented in medical record in placebo vs intervention group
Measured: at 12 months corrected
Number of outpatient visits for infant during first 12 months corrected
Number of outpatient visits recorded during first 12 months corrected in placebo vs. intervention groups
Measured: birth through12 months corrected
Failure to thrive in for infant
Presence or absence of diagnosis "failure to thrive" in medical record through first 12 months corrected in placebo vs intervention
Measured: birth through 12 months corrected
number of inpatient days for infant through 12 months corrected
number of inpatient days for infant through 12 months corrected in intervention vs placebo
Measured: birth through 12 months corrected
Indication of infant developmental delay in medical record from birth through 12 months corrected
Presence or absence of any indication of developmental delay recorded by physician in the medical record through 12 months corrected in intervention vs placebo groups
Measured: birth through 12 months corrected
Number of antibiotic prescriptions for infant through first 12 months corrected
Number of antibiotic prescriptions for infant through first 12 months corrected in intervention vs placebo
Measured: birth through 12 months corrected
Documented infant feeding plan through first year
Documented infant feeding plan through first year. Exclusive breastfeeding, formula and breastfeeding or exclusive formula
Measured: birth through 12 months corrected
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start1 Feb 2019
- Primary completion1 Dec 2020 (estimated)
- Study completion1 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for InflammationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double Blinded, Randomized, Placebo controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Walter Reed National Military Medical Center
- Sponsor type
- US federal agency
- Collaborators
- National Institutes of Health (NIH), dsm-firmenich Switzerland AG, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Peter F Knickerbocker, DO, Principal investigator, Walter Reed National Miltary Medical CenterKim Hee-Yong, PhD, Study director, NIH/ NIAAACarl Hunt, MD, Study chair, Uniformed Services University of the Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04069195
- Sponsor's protocol ID
- WRNMMC-2018-0126
- Status last verified
- Aug 2019
- First submitted
- 13 Feb 2018
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All study data will be coded and master key will only be available to study personnel at Walter Reed National Military Medical Center. No decoded study data will be provided to the NIH/NIAAA
Publications
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.
PubMed 22585914Martin 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.
PubMed 21658712Ma 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.
PubMed 23044165Hofer 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.
PubMed 23994220De 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.
PubMed 11548181Cheng 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.
PubMed 25269386Kim 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.
PubMed 22959887Meijerink 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.
PubMed 24780080Balvers 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.
PubMed 20601112Makrides 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.
PubMed 20959577Dunstan 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.
PubMed 17185423
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo Controlled Trial of Docosahexaenoic Acid (DHA) Supplementation in High Risk Pregnancies
- ClinicalTrials.gov ID
- NCT04069195
- Acronym / sponsor ID
- WRNMMC-2018-0126
- Conditions
- Inflammation, Pregnancy Related
- Keywords
- Inflammation, DHA, Pregnancy, preterm, overweight
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Walter Reed National Military Medical CenterUS federal agency
- Collaborators
- National Institutes of Health (NIH), dsm-firmenich Switzerland AG, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Dec 2020 (estimated)
- Study completion
- 1 Dec 2020 (estimated)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
All pregnant women meeting the inclusion/exclusion criteria will be identified at the time of their regular OB appointments between the 8th and the 14th week of pregnancy (+/- 3 days) Research team members will approach potential subjects to explain the study and obtain consent for their participation Patients who give their consent for enrollment will be asked to complete a dietary survey at the time of enrollment Patients will be given a paper script for study drug to be taken to the Walter Reed Military Medical Center pharmacy to obtain study drug The Investigational Pharmacy will randomize the patients in double blinded fashion to the intervention group or placebo group.
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 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 The placebo and intervention drugs will be packaged in the same capsule membrane and will be indistinguishable by color, shape, or taste.
Patients will be instructed to take 1 capule PO daily until their child is delivered Patients will be issued a 3 month supply of study drug at enrollment and will get refills from the investigational pharmacy
≤5ml of whole blood will be obtained from each subject at enrollment and at 26-30 weeks gestation (+/- 3 days), as part of a routine blood sampling. It is standard of care to collect blood at this point in pregnancy for lab evaluation. The additional tube of blood collected for this study is for research purposes only and not part of the standard of care. This sample will be centrifuged, and the separated plasma will be labeled and frozen at -80° C pending transport to Dr. Kim's lab at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for bulk analyses.
At delivery, ≤5ml of umbilical cord blood will be obtained from an umbilical artery and from the umbilical vein. These samples will be processed and stored in a similar fashion as the earlier samples. Cord blood is a medical waste product, and collection will therefore have no adverse effect for either mother or newborn. It is standard of care to collect cord blood by OB request for lab evaluation. Collecting additional cord blood for this study anaylsis is for research purposes only All enrollees will complete a dietary survey upon enrollment at 8-14 weeks (+/- 3 days), at 26-30th week of pregnancy (+/- 3 days), and during the delivery admission. This survey will also include the subject's self-report on compliance with taking the study supplement All plasma samples collected will be processed at Dr. Kim's National Institute on Alcohol Abuse and Alcoholism/ National Insititute of Health (NIAAA/NIH) laboratories The Cytokine Assays for IL-6, Il-10, TNF- alpha will be run in Dr Kim's lab using Ensyme Linked Immunosorbent Assay (ELISA) testing The DHA and Synaptamide levels will be analyzed in Dr. Kim's lab using High performance liquid chromatrography with tandem mass spectrometry All babies from multiple birth pregnancies will be enrolled in this study The offspring of enrolled women will be followed through 12 months corrected age to assess the longer term outcomes of study intervention Information will be collected from the maternal medical record at time of enrollment, infant delivery and postpartum discharge.
Information will be collected from the infant medical record at time of birth discharge, and 12 months corrected age.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double Blinded, Randomized, Placebo controlled
| Arm | Type | Receives |
|---|---|---|
| DHA supplement | Active comparator | Dietary Supplement: DHA supplementPatients 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. |
| corn oil: Soybean oil placebo | Placebo comparator | Dietary Supplement: Corn Oil: Soybean OilPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DHA supplementAlso: Docosahexaenoic AcidPatient'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 | Dietary supplement | DHA supplement |
| Corn Oil: Soybean OilPatient'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 | Dietary supplement | corn oil: Soybean oil placebo |
Primary outcome
Measure DHA
Time frame: Sample obtained between 8-14 weeks of pregnancy
Measurement of maternal plasma DHA using tandem mass spec
Measure DHA
Time frame: Sample obtained between 26-30 weeks of pregnancy
Measurement of maternal plasma DHA using tandem mass spec
Measure DHA
Time frame: Sample obtained from cord blood at time of infant delivery
Measurement of fetal plasma DHA using tandem mass spec
Measure synaptamide
Time frame: Sample obtained between 8-14 weeks of pregnancy
Measurement of maternal plasma synaptamide using tandem mass spec
Measure synaptamide
Time frame: Sample obtained between 26-30 weeks of pregnancy
Measurement of maternal plasma synaptamide using tandem mass spec
Measure synaptamide
Time frame: Sample obtained from cord blood at time of infant delivery
Measurement of fetal plasma synaptamide using tandem mass spec
Measure inflammatory biomarkers
Time frame: Sample obtained between 8-14 weeks of pregnancy
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measure inflammatory biomarkers
Time frame: Sample obtained between 26-30 weeks of pregnancy
Measurement of plasma cytokine levels using ELISA human cytokine panel
Measure inflammatory biomarkers
Time frame: Sample obtained from cord blood at time of infant delivery
Measurement of plasma cytokine levels using ELISA human cytokine panel
42 secondary outcomes
Maternal Gestational weight gain at end of pregnancy in placebo vs. DHA supplement groups
Time frame: At time of infant delivery
Infant delivery method
Time frame: At time of infant delivery
Delivery complications
Time frame: at time of infant delivery
Maternal death
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 6 months after infant delivery
Pre-eclampsia
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
chorioamionitis
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
Gestational Diabetes Melitus
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
non-gestational Diabetes mellitus
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
Preterm Premature Rupture of Membranes
Time frame: From enrollment in study at 8-14 weeks of pregnancy until 42 weeks of pregnancy or day of infant delivery, whichever happens first
going past due dates
Time frame: during last month of pregnancy
Placental pathology
Time frame: at time of delivery
Head circumference at birth
Time frame: At time of infant birth
Length at birth
Time frame: At time of infant birth
weight at birth
Time frame: At time of infant birth
Gestational age at birth
Time frame: At time of infant birth
APGAR score at 1 min
Time frame: At time of infant birth
APGAR score at 5 min
Time frame: At time of infant birth
Resuscitation beyond warm/dry stimulate at birth
Time frame: At time of infant birth
Presence or absence or requirement for respiratory assistance within the first 24 hours after birth
Time frame: From NICU admission to 24 hours after birth
Days of antibiotic exposure during birth hospitalization
Time frame: During birth admission up to 8 months of chronologic age or discharge from hospital whichever happens sooner
NICU admission
Time frame: Within the first 5 days of infant's life
Duration of birth admission
Time frame: Birth through 12 months of age or infant discharge, whichever occurs sooner
Requirement for phototherapy during birth admission
Time frame: Birth through 14 days of infant life
Culture proven sepsis
Time frame: From birth through 12 months or until infant discharge whichever occurs sooner
Infant Death
Time frame: From birth through 12 months or until infant discharge whichever occurs sooner
Weight at infant hospital discharge
Time frame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
head circumference at infant hospital discharge
Time frame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
Length at infant hospital discharge
Time frame: At time of infant's first discharge from hospital or at 12 months corrected, whichever comes first
Feeding plan at infant discharge
Time frame: At 12 months chronological if still admitted or at infant discharge, whichever occurs sooner
Infant diagnosis in medical record
Time frame: at 12 months corrected
infant weight at 6 months corrected age
Time frame: at 6 months corrected
infant weight at 12 months corrected age
Time frame: at 12 months corrected
head circumferene weight at 6 months corrected age
Time frame: at 6 months corrected
head circumference weight at 12 months corrected age
Time frame: at 12 months corrected
Length weight at 6 months corrected age
Time frame: at 6 months corrected
Length weight at 12 months corrected age
Time frame: at 12 months corrected
Number of outpatient visits for infant during first 12 months corrected
Time frame: birth through12 months corrected
Failure to thrive in for infant
Time frame: birth through 12 months corrected
number of inpatient days for infant through 12 months corrected
Time frame: birth through 12 months corrected
Indication of infant developmental delay in medical record from birth through 12 months corrected
Time frame: birth through 12 months corrected
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Background: PubMed 22585914Valentine 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.
- Background: PubMed 21658712Martin 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.
- Background: PubMed 23044165Ma 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.
- Background: PubMed 23994220Hofer 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.
- Background: PubMed 11548181De 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.
- Background: PubMed 25269386Cheng 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.
- Background: PubMed 22959887Kim 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.
- Background: PubMed 24780080Meijerink 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.
- Background: PubMed 20601112Balvers 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.
- Background: PubMed 20959577Makrides 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.
- Background: PubMed 17185423Dunstan 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.
- Individual participant dataSharing planned: No. All study data will be coded and master key will only be available to study personnel at Walter Reed National Military Medical Center. No decoded study data will be provided to the NIH/NIAAA
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter F Knickerbocker, DO principal investigator
Walter Reed National Miltary Medical Center
Kim Hee-Yong, PhD study director
NIH/ NIAAA
Carl Hunt, MD study chair
Uniformed Services University of the Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DHA supplement and Corn Oil: Soybean Oil in people with Inflammation and Pregnancy Related, run by Walter Reed National Military Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter F Knickerbocker, DO (215-298-2476, peteknickerbocker@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure DHA (time frame: Sample obtained between 8-14 weeks of pregnancy). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04069195, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.