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

NCT ID: NCT00135902

Last Updated: 2019-07-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-02-28

Study Completion Date

2008-03-31

Brief Summary

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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

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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.

Conditions

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Preterm Birth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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17P plus Omega-3 Supplement

Weekly 17 alpa hydroxyprogesterone caproate (17p) injections plus Omega 3 supplements, 4 capsules per day for up to 5 weeks. Each capsule contained 200 mg of docosahexaenoic acid (DHA) and 300 mg of eicosapentaenoic acid (EPA).

Group Type ACTIVE_COMPARATOR

17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement

Intervention Type DRUG

Participants receive a weekly progesterone injection (17 alpha hydroxyprogesterone caproate) up to 37 weeks gestation and take daily Omega-3 supplements.

17P plus Placebo Supplement

Weekly 17 alpa hydroxyprogesterone caproate (17p) injections plus placebo capsules, 4 capsules per day for up to 5 weeks

Group Type PLACEBO_COMPARATOR

17 alpha-hydroxy progesterone caproate and Placebo supplement

Intervention Type DRUG

Participants receive a weekly progesterone injection (17P) up to 37 weeks gestation and take daily placebo supplements

Interventions

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17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement

Participants receive a weekly progesterone injection (17 alpha hydroxyprogesterone caproate) up to 37 weeks gestation and take daily Omega-3 supplements.

Intervention Type DRUG

17 alpha-hydroxy progesterone caproate and Placebo supplement

Participants receive a weekly progesterone injection (17P) up to 37 weeks gestation and take daily placebo supplements

Intervention Type DRUG

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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

NIH

Sponsor Role collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Menachem Miodovnik, MD

Role: PRINCIPAL_INVESTIGATOR

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

Elizabeth A Thom, PhD

Role: PRINCIPAL_INVESTIGATOR

George Washington University Biostatistics Center

Margaret Harper, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

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University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Columbia University

New York, New York, United States

Site Status

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

Case Western University

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Drexel University

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Brown University

Providence, Rhode Island, United States

Site Status

University of Utah Medical Center

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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. doi: 10.1056/NEJMoa035140.

Reference Type BACKGROUND
PMID: 12802023 (View on PubMed)

Olsen SF, Secher NJ, Bjornsson 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. doi: 10.1034/j.1600-0412.2003.00334.x. No abstract available.

Reference Type BACKGROUND
PMID: 14616269 (View on PubMed)

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

Reference Type BACKGROUND

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. doi: 10.1111/j.1471-0528.2000.tb13235.x.

Reference Type BACKGROUND
PMID: 10740336 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11859044 (View on PubMed)

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. doi: 10.1016/s0002-9378(97)70620-3.

Reference Type BACKGROUND
PMID: 9125620 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14657879 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9637532 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12562875 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9481127 (View on PubMed)

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.

Reference Type RESULT
PMID: 20093894 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23635681 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21508745 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21173653 (View on PubMed)

Related Links

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Other Identifiers

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U10HD021410

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027869

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027917

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027860

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD027915

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034208

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD034136

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040500

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040544

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040545

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040560

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD040512

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10HD036801

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HD36801-Omega-3

Identifier Type: -

Identifier Source: org_study_id

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