Clinical trial NCT00135902: Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in High Risk Pregnancies
Official title: A Randomized Trial of Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in Pregnancies at High Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Preterm Birth
Keywords: Preterm birth
Progesterone
Omega-3 fatty acid
Pregnancy
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2005-08-26
Enrollment: 800
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P) found significant effectiveness for 17P in preventing recurrent preterm birth. However, the group who received 17P in this trial still had a high rate of preterm birth. Several reports have shown that dietary supplementation of fish oil, which is rich in Omega-3 fatty acids, reduces the risk of preterm birth. This trial tests whether adding the Omega-3 supplement to 17P therapy has the potential for further reducing the risk of preterm birth in women who have previously had a spontaneous preterm delivery. The trial will compare Omega-3 fatty acid with placebo in women receiving 17P therapy. The hypothesis being tested is: "Among women at high risk for preterm birth receiving weekly injections of 17P, the addition of Omega-3 nutritional supplement will further reduce the rate of preterm birth."

Detailed description: Preterm birth is the leading cause of perinatal mortality and morbidity. In a recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P), the National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network found the treatments significantly beneficial in the prevention of recurrent preterm birth. Other studies have shown that fish oil supplementation can reduce the risk for preterm birth. The purpose of this study is to determine whether Omega-3, a polyunsaturated fatty acid nutritional supplement, in addition to injections of 17P, further decreases the rate of preterm birth in women at risk.

This study is a randomized, double-masked clinical trial with two study arms: a daily supplement of Omega-3 capsules containing 800 mg of DHA and 1200 mg of EPA or a daily supplement of a matching placebo. All patients will also receive weekly injections of 17P. Eight hundred pregnant women with a history of previous preterm delivery will be recruited for this study. After successfully completing a compliance run-in, which can begin as early as 15 weeks gestation, patients will be randomized and begin treatment between 16 and 22 weeks gestation. They will remain on study drug until 36 week and 6 days or delivery, whichever occurs first. Blood will be drawn at randomization and at a monthly visit falling between 25-29 weeks of gestation to test for compliance, to analyze genetic polymorphisms and to determine whether Omega-3 affects the production of inflammatory cytokines.

Eligibility criteria: Inclusion Criteria:

* Documented history of previous singleton spontaneous birth
* Singleton pregnancy
* Gestational age at randomization between 16 and 22 weeks

Exclusion Criteria:

* Major fetal anomaly or demise
* Regular intake of fish oil supplements
* Daily use of nonsteroidal anti-inflammatory agents
* Allergy to fish or fish products
* Gluten intolerant
* Heparin use or known thrombophilia
* Hemophilia
* Planned termination
* Current hypertension or current use of antihypertensive medications
* Type D, F or R diabetes
* Maternal medical complications
* Current or planned cerclage
* Illicit drug or alcohol abuse during current pregnancy
* Delivery at a non-Network hospital
* Participation in another pregnancy intervention study
* Participation in this trial in a previous pregnancy

Primary outcomes:
measure: Delivery before than 37 weeks gestation
timeFrame: Up to 37 weeks gestation
Secondary outcomes:
measure: Delivery before 35 weeks gestation
timeFrame: Up to 35 weeks gestation
measure: Delivery before 32 weeks gestation
timeFrame: Up to 32 weeks gestation
measure: Delivery after 40 weeks gestation
timeFrame: 40 weeks gestation or greater
measure: Pregnancy loss or neonatal death
timeFrame: Randomization to hospital discharge (up to 25 weeks)
measure: Gestational age at delivery
timeFrame: Delivery
measure: Birth weight less than 2,500 grams
timeFrame: Birth
measure: Birth weight less than 1,500 grams
timeFrame: Birth
measure: Birth size small for gestational age at less than 10th percentile
timeFrame: Birth
measure: Birth size large for gestational age at more than 90th percentile
timeFrame: Birth
measure: Admission to neonatal intensive care or intermediate care nursery
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal retinopathy of prematurity
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Intraventricular Hemorrhage at any grade
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Intraventricular Hemorrhage Grade 3 or 4
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal patent ductus arteriosus
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal necrotizing enterocolitis
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal sepsis
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal respiratory distress syndrome
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal surfactant use
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal bronchopulmonary dysplasia
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal transient tacypnea
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal supplemental oxygen support
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
measure: Neonatal ventilator support
timeFrame: Delivery through neonatal discharge (up to 2 weeks)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Magee Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
Study officials:
affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Menachem Miodovnik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: George Washington University Biostatistics Center
name: Elizabeth A Thom, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Margaret Harper, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ. 2002 Feb 23;324(7335):447. doi: 10.1136/bmj.324.7335.447.
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citation: Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol. 2003 Dec;112(6):1178-84. doi: 10.1016/j.jaci.2003.09.009.
citation: Cadroy Y, Dupouy D, Boneu B. Arachidonic acid enhances the tissue factor expression of mononuclear cells by the cyclo-oxygenase-1 pathway: beneficial effect of n-3 fatty acids. J Immunol. 1998 Jun 15;160(12):6145-50.
citation: Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003 Mar;44(3):479-86. doi: 10.1194/jlr.M200361-JLR200. Epub 2002 Dec 1.
citation: Calder PC. Dietary fatty acids and the immune system. Nutr Rev. 1998 Jan;56(1 Pt 2):S70-83. doi: 10.1111/j.1753-4887.1998.tb01648.x. No abstract available.
citation: Harper M, Thom E, Klebanoff MA, Thorp J Jr, Sorokin Y, Varner MW, Wapner RJ, Caritis SN, Iams JD, Carpenter MW, Peaceman AM, Mercer BM, Sciscione A, Rouse DJ, Ramin SM, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial. Obstet Gynecol. 2010 Feb;115(2 Pt 1):234-242. doi: 10.1097/AOG.0b013e3181cbd60e.
citation: Harper M, Li L, Zhao Y, Klebanoff MA, Thorp JM Jr, Sorokin Y, Varner MW, Wapner RJ, Caritis SN, Iams JD, Carpenter MW, Peaceman AM, Mercer BM, Sciscione A, Rouse DJ, Ramin SM, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network*. Change in mononuclear leukocyte responsiveness in midpregnancy and subsequent preterm birth. Obstet Gynecol. 2013 Apr;121(4):805-811. doi: 10.1097/AOG.0b013e3182878a80.
citation: Klebanoff MA, Harper M, Lai Y, Thorp J Jr, Sorokin Y, Varner MW, Wapner RJ, Caritis SN, Iams JD, Carpenter MW, Peaceman AM, Mercer BM, Sciscione A, Rouse DJ, Ramin SM, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Fish consumption, erythrocyte fatty acids, and preterm birth. Obstet Gynecol. 2011 May;117(5):1071-1077. doi: 10.1097/AOG.0b013e31821645dc.
citation: Harper M, Zheng SL, Thom E, Klebanoff MA, Thorp J Jr, Sorokin Y, Varner MW, Iams JD, Dinsmoor M, Mercer BM, Rouse DJ, Ramin SM, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Cytokine gene polymorphisms and length of gestation. Obstet Gynecol. 2011 Jan;117(1):125-130. doi: 10.1097/AOG.0b013e318202b2ef.