Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity

NCT ID: NCT02486042

Last Updated: 2022-12-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2019-12-31

Brief Summary

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Retinopathy of prematurity (ROP) is a blinding disease affecting infants born prematurely. These infants do not have enough essential fatty acids to structurally support the retina, the nerve tissue in the eye which allows us to see. A recent study showed that giving omega-3 (n-3) fatty acids to these infants soon after birth made them less likely to need invasive treatments for eye disease. This research trial will give young infants born prematurely n-3 fish oil treatment and look at how this changes factors in the blood that promote disease. Detailed blood studies comparing infants with and without ROP will be performed and the infants will be followed over time to assess their eye development.

Detailed Description

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Approximately 517,000 infants are born prematurely every year. As low birth weight and premature infants are surviving longer, they are at risk of developing severe retinopathy of prematurity (ROP).

ROP is a disease of the eye affecting prematurely-born babies. It is thought to be caused by disorganized growth of retinal blood vessels which may result in scarring and retinal detachment. ROP can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. ROP is the leading cause of irreversible childhood blindness in the United States. As such, all preterm babies are at risk for ROP, and very low birth weight is an important risk factor.

Researchers have found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet of mice with eye disease similar to ROP had reduced areas of blood vessel loss and abnormal blood vessel growth. These findings represent new evidence suggesting the possibility that omega-3 fatty acids act as protective factors in diseases that affect retinal blood vessels.

Omega-3 fatty acids make compounds that protect against the growth of abnormal blood vessels by preventing inflammation.

In two European studies, this treatment decreased the risk of needing laser treatment in the eye for ROP. This study has not yet been repeated in the United States. The purpose of this study is to learn how omega-3 fatty acid supplementation in low birth weight infants changes the blood profile of infants receiving this nutritional treatment.

Infants are enrolled in this study shortly after birth and receive IV and/or oral supplementation until they are full term or the retinal blood vessels have completely developed, shortly after term. Once the treatment is over, these infants will continue to be followed for growth and development of their eyes.

Conditions

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Retinopathy of Prematurity

Keywords

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ROP Premature infant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Investigators

Study Groups

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Standard of Care (Standard Nutrition)

Infants in this group will receive standard lipids (predominantly Omega-6 fatty acids).

Group Type ACTIVE_COMPARATOR

Standard lipids (primarily omega-6 fatty acids)

Intervention Type DIETARY_SUPPLEMENT

Infants will receive nutritional supplementation with standard intralipid, composed primarily of omega-6 fatty acids.

Omegaven

Infants in this group will receive lipid supplementation with omega-3 fatty acids.

Group Type EXPERIMENTAL

Omegaven

Intervention Type DRUG

Infants will receive nutritional supplementation with omega-3 fatty acids (omegaven).

Interventions

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Omegaven

Infants will receive nutritional supplementation with omega-3 fatty acids (omegaven).

Intervention Type DRUG

Standard lipids (primarily omega-6 fatty acids)

Infants will receive nutritional supplementation with standard intralipid, composed primarily of omega-6 fatty acids.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Omega-3 Intralipid

Eligibility Criteria

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Inclusion Criteria

* Infants born less than or equal to 30 weeks gestation or less than 1500 g at birth

Exclusion Criteria

* Patients with liver disease as tested by liver function tests (LFTs)
* ≤ 500 grams birthweight
Maximum Eligible Age

7 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Hartwell Foundation

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role lead

Responsible Party

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Shira Robbins

Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shira L. Robbins, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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University of California, San Diego Jacobs Medical Center

La Jolla, California, United States

Site Status

Countries

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United States

References

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Gould JF, Smithers LG, Makrides M. The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Mar;97(3):531-44. doi: 10.3945/ajcn.112.045781. Epub 2013 Jan 30.

Reference Type BACKGROUND
PMID: 23364006 (View on PubMed)

Clandinin MT, Chappell JE, Heim T, Swyer PR, Chance GW. Fatty acid utilization in perinatal de novo synthesis of tissues. Early Hum Dev. 1981 Sep;5(4):355-66. doi: 10.1016/0378-3782(81)90016-5.

Reference Type BACKGROUND
PMID: 7285840 (View on PubMed)

Arsic A, Vucic V, Prekajski N, Tepsic J, Ristic-Medic D, Velickovic V, Glibetic M. Different fatty acid composition of serum phospholipids of small and appropriate for gestational age preterm infants and of milk from their mothers. Hippokratia. 2012 Jul;16(3):230-5.

Reference Type BACKGROUND
PMID: 23935289 (View on PubMed)

Pawlik D, Lauterbach R, Walczak M, Hurkala J, Sherman MP. Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study. JPEN J Parenter Enteral Nutr. 2014 Aug;38(6):711-6. doi: 10.1177/0148607113499373. Epub 2013 Aug 20.

Reference Type BACKGROUND
PMID: 23963690 (View on PubMed)

Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N Jr, Serhan CN, Smith LEH. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007 Jul;13(7):868-873. doi: 10.1038/nm1591. Epub 2007 Jun 24.

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PMID: 17589522 (View on PubMed)

Stahl A, Sapieha P, Connor KM, Sangiovanni JP, Chen J, Aderman CM, Willett KL, Krah NM, Dennison RJ, Seaward MR, Guerin KI, Hua J, Smith LE. Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circ Res. 2010 Aug 20;107(4):495-500. doi: 10.1161/CIRCRESAHA.110.221317. Epub 2010 Jul 15.

Reference Type BACKGROUND
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Smith LE. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5177-82. doi: 10.1167/iovs.08-2584. Epub 2008 Aug 15. No abstract available.

Reference Type BACKGROUND
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SanGiovanni JP, Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005 Jan;24(1):87-138. doi: 10.1016/j.preteyeres.2004.06.002.

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PMID: 15555528 (View on PubMed)

Pawlik D, Lauterbach R, Turyk E. Fish-oil fat emulsion supplementation may reduce the risk of severe retinopathy in VLBW infants. Pediatrics. 2011 Feb;127(2):223-8. doi: 10.1542/peds.2010-2427. Epub 2011 Jan 3.

Reference Type BACKGROUND
PMID: 21199856 (View on PubMed)

Klein CJ, Havranek TG, Revenis ME, Hassanali Z, Scavo LM. Plasma fatty acids in premature infants with hyperbilirubinemia: before-and-after nutrition support with fish oil emulsion. Nutr Clin Pract. 2013 Feb;28(1):87-94. doi: 10.1177/0884533612469989.

Reference Type BACKGROUND
PMID: 23319354 (View on PubMed)

Heird WC. The role of polyunsaturated fatty acids in term and preterm infants and breastfeeding mothers. Pediatr Clin North Am. 2001 Feb;48(1):173-88. doi: 10.1016/s0031-3955(05)70292-3.

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PMID: 11236724 (View on PubMed)

O'Connor DL, Hall R, Adamkin D, Auestad N, Castillo M, Connor WE, Connor SL, Fitzgerald K, Groh-Wargo S, Hartmann EE, Jacobs J, Janowsky J, Lucas A, Margeson D, Mena P, Neuringer M, Nesin M, Singer L, Stephenson T, Szabo J, Zemon V; Ross Preterm Lipid Study. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics. 2001 Aug;108(2):359-71. doi: 10.1542/peds.108.2.359.

Reference Type BACKGROUND
PMID: 11483801 (View on PubMed)

Fleith M, Clandinin MT. Dietary PUFA for preterm and term infants: review of clinical studies. Crit Rev Food Sci Nutr. 2005;45(3):205-29. doi: 10.1080/10408690590956378.

Reference Type BACKGROUND
PMID: 16048149 (View on PubMed)

Smithers LG, Gibson RA, McPhee A, Makrides M. Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials. Am J Clin Nutr. 2008 Apr;87(4):912-20. doi: 10.1093/ajcn/87.4.912.

Reference Type BACKGROUND
PMID: 18400714 (View on PubMed)

Fewtrell MS, Morley R, Abbott RA, Singhal A, Isaacs EB, Stephenson T, MacFadyen U, Lucas A. Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. Pediatrics. 2002 Jul;110(1 Pt 1):73-82. doi: 10.1542/peds.110.1.73.

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Clandinin MT, Van Aerde JE, Merkel KL, Harris CL, Springer MA, Hansen JW, Diersen-Schade DA. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. J Pediatr. 2005 Apr;146(4):461-8. doi: 10.1016/j.jpeds.2004.11.030.

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Schulzke SM, Patole SK, Simmer K. Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD000375. doi: 10.1002/14651858.CD000375.pub4.

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PMID: 21328248 (View on PubMed)

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Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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140253

Identifier Type: -

Identifier Source: org_study_id