Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in High Risk Pregnancies

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ClinicalTrials.gov Identifier: NCT00135902

Recruitment Status : Completed

First Posted : August 26, 2005

Last Update Posted : October 3, 2016

Sponsor:

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Information provided by (Responsible Party):

The George Washington University Biostatistics Center

Study Description

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."

Condition or disease	Intervention/treatment	Phase
Preterm Birth	Drug: 17 alpha-Hydroxyprogesterone Caproate and Omega-3 fish oils	Phase 3

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	800 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Prevention
Official Title:	A Randomized Trial of Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in Pregnancies at High Risk
Study Start Date :	February 2005
Actual Primary Completion Date :	March 2007
Actual Study Completion Date :	March 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Hydroxyprogesterone Hydroxyprogesterone caproate Omega-3 Fatty Acids

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

Delivery less than 37 completed weeks gestation including any miscarriages occurring after randomization

Secondary Outcome Measures :

MATERNAL: Delivery less than 35 weeks
Delivery less than 32 weeks
Spontaneous preterm delivery
Indicated preterm delivery
Tocolytic therapy
Time from randomization to delivery
Delivery on or after 41 weeks of gestation
Occurrence of gestational hypertension or preeclampsia
Maternal hospital days
Fatty acid constituents in maternal plasma samples, before and after supplementation
Postpartum hemorrhage
FETAL AND NEONATAL: Fetal and neonatal death
Gestational age at delivery
Small for gestational age
Birth weight
Apgar score at 1 and 5 minutes
Number of days of neonatal respiratory therapy
Admission to NICU and total number of days in hospital
Intraventricular hemorrhage
Retinopathy of prematurity
Necrotizing enterocolitis
Deep infection
Periventricular leukomalacia
Bronchopulmonary dysplasia
Respiratory distress syndrome
Composite neonatal outcome

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00135902

Locations


United States, Alabama
University of Alabama - Birmingham
Birmingham, Alabama, United States
United States, Illinois
Northwestern University
Chicago, Illinois, United States
United States, Michigan
Wayne State University
Detroit, Michigan, United States
United States, New York
Columbia University
New York, New York, United States
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
Wake Forest University School of Medicine
Winston Salem, North Carolina, United States
United States, Ohio
Case Western University
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States
University of Pittsburgh Magee Womens Hospital
Pittsburgh, Pennsylvania, United States
United States, Rhode Island
Brown University
Providence, Rhode Island, United States
United States, Texas
University of Texas - Southwest
Dallas, Texas, United States
United States, Utah
University of Utah Medical Center
Salt Lake City, Utah, United States

Sponsors and Collaborators

The George Washington University Biostatistics Center

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	Uma Reddy, MD	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator:	Elizabeth A Thom, PhD	George Washington University Biostatistics Center
Principal Investigator:	Margaret Harper, MD	Wake Forest University Health Sciences

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. Erratum in: N Engl J Med. 2003 Sep 25;349(13):1299.

Olsen SF, Secher NJ, Björnsson S, Weber T, Atke A. The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial? Acta Obstet Gynecol Scand. 2003 Nov;82(11):978-82. Review.

Duley L. Prophylactic fish oil in pregnancy. The Cochrane Pregnancy & Childbirth Database (Issue 2, 1995).

Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG. 2000 Mar;107(3):382-95.

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.

Reece MS, McGregor JA, Allen KG, Harris MA. Maternal and perinatal long-chain fatty acids: possible roles in preterm birth. Am J Obstet Gynecol. 1997 Apr;176(4):907-14.

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.

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.

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. Epub 2002 Dec 1.

Calder PC. Dietary fatty acids and the immune system. Nutr Rev. 1998 Jan;56(1 Pt 2):S70-83. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Maternal-Fetal Medicine Units Network. Change in mononuclear leukocyte responsiveness in midpregnancy and subsequent preterm birth. Obstet Gynecol. 2013 Apr;121(4):805-11. doi: 10.1097/AOG.0b013e3182878a80.

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):1071-7. doi: 10.1097/AOG.0b013e31821645dc.

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):125-30. doi: 10.1097/AOG.0b013e318202b2ef.

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):234-42. doi: 10.1097/AOG.0b013e3181cbd60e.


Responsible Party:	The George Washington University Biostatistics Center
ClinicalTrials.gov Identifier:	NCT00135902 History of Changes
Other Study ID Numbers:	HD36801-Omega-3 HD21410 HD27869 HD27917 HD27860 HD27915 HD34116 HD34208 HD34136 HD40500 HD40485 HD40544 HD40545 HD40560 HD40512
First Posted:	August 26, 2005 Key Record Dates
Last Update Posted:	October 3, 2016
Last Verified:	September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	The data will be shared after completion and publication of the main analyses in accordance with NIH policy. The contact to obtain datasets is mfmudatasets@bsc.gwu.edu.

Keywords provided by The George Washington University Biostatistics Center:


Preterm birth Progesterone Omega-3 fatty acid Pregnancy

Additional relevant MeSH terms:


Premature Birth Obstetric Labor, Premature Obstetric Labor Complications Pregnancy Complications 17-alpha-hydroxy-progesterone caproate 11-hydroxyprogesterone	Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Progestins Hormones

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