Retinopathy of PrematurityPhase 2NCT02486042
Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity
A Phase 2 study testing Omegaven and Standard lipids (primarily omega-6 fatty acids) in people with Retinopathy of Prematurity, run by University of California, San Diego at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 7 days
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- Omegaven and Standard lipids (primarily omega-6 fatty acids)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 7 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants born less than or equal to 30 weeks gestation or less than 1500 g at birth
Who cannot join
- Patients with liver disease as tested by liver function tests (LFTs)
- ≤ 500 grams birthweight
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego Jacobs Medical Center
La Jolla, California, 92037
About this study
Official title: Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity: Proposal for a Prospective Randomized Controlled Masked Clinical Trial With Lipidomic and Transcriptomic Analyses
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.
Read the detailed description
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
- Retinopathy of Prematurity
- Being tested
- Omegaven, Standard lipids (primarily omega-6 fatty acids)
- Keywords
- ROP, Premature infant
- Medical subject headings
- Retinopathy of Prematurity, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OmegavenDrug
Also called Omega-3
Infants will receive nutritional supplementation with omega-3 fatty acids (omegaven).
Standard lipids (primarily omega-6 fatty acids)Dietary supplement
Also called Intralipid
Infants will receive nutritional supplementation with standard intralipid, composed primarily of omega-6 fatty acids.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (Standard Nutrition) | Active comparator | Infants in this group will receive standard lipids (predominantly Omega-6 fatty acids). Receives: Dietary Supplement: Standard lipids (primarily omega-6 fatty acids) |
| Omegaven | Experimental | Infants in this group will receive lipid supplementation with omega-3 fatty acids. Receives: Drug: Omegaven |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T0
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis.
Biomarker significance:
STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk
PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk
STC-1: stress response protein. Higher STC-1=lower ROP risk
Delta Ct meaning:
qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Measured: T0 as defined in study protocol: prior to parental nutrition, within first three days of life
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T1
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis.
Biomarker significance:
STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk
PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk
STC-1: stress response protein. Higher STC-1=lower ROP risk
Delta Ct meaning:
qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Measured: T1 as defined in study protocol: 5 days after parenteral nutrition is started; grace period +/-3 days therefore total 2-8 days after parenteral nutrition started.
Changes in mRNA Expression in Blood of STAT3, PPAR-gamma, and STC-1 at T2
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis.
Biomarker significance:
STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk
PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk
STC-1: stress response protein. Higher STC-1=lower ROP risk
Delta Ct meaning:
qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Measured: T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Changes in mRNA Expression in Blood of STAT3 and PPAR-ɣ at T3
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis.
Biomarker significance:
STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk
PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk
Delta Ct meaning:
qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Measured: T3 as defined in study protocol: Prior to discharge from hospital coinciding with time that ROP may be present, ≥35 weeks adjusted age.
Secondary outcomes (3)
Pilot Assay of Basic Fatty Acid Concentrations in Blood at Time T2
We measured concentrations of basic fatty acids in the blood plasma samples: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA). Blood samples were processed by the University of California San Diego lipidomics core and fatty acid concentrations in pmol/ml plasma were determined using gas chromatography-mass spectrometry.
Measured: T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Percentage of Eyes at the Furthest Stage of ROP Achieved
Furthest severity stage of ROP achieved by patients in Arm 1 compared to Arm 2, per eye as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age.
Severity staging was determined in an eye exam per accepted clinical guidelines by a trained clinician and retinopathy of prematurity specialist. Briefly, staging is assigned based on the junction of the vascularized and avascular retina when viewed using indirect ophthalmoscopy. The higher the stage, the more severe the ROP. Per the American Association for Pediatric Ophthalmology and Strabismus,
- Stage 0: no clear demarcation line between vascularized and non-vascularized retina
- Stage 1: demarcation line that separates normal from premature retina
- Stage 2: ridge with height and width
- Stage 3: growth of fragile new abnormal blood vessels
Measured: approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)
Number of Patients Requiring Laser Treatment in Arm 1 Versus Arm 2
Number of patients with retinopathy of prematurity severe enough to require laser treatment by the adjusted age of 40 weeks, as assessed by weekly ROP screenings from approximately 31 weeks through 40 weeks adjusted age.
Measured: approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startMar 2014
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- The Hartwell Foundation
- Responsible party
- Principal investigator, Shira Robbins, University of California, San Diego
- Investigators
- Shira L. Robbins, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02486042
- Sponsor's protocol ID
- 140253
- Status last verified
- Nov 2022
- First submitted
- 26 Jun 2015
- Last updated
- 29 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23364006Clandinin 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.
PubMed 7285840Arsic 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.
PubMed 23935289Pawlik 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.
PubMed 23963690Connor 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.
PubMed 17589522Stahl 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.
PubMed 20634487Smith 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.
PubMed 18708611SanGiovanni 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.
PubMed 15555528Pawlik 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.
PubMed 21199856Klein 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.
PubMed 23319354Heird 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.
PubMed 11236724O'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.
PubMed 11483801Fleith 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.
PubMed 16048149Smithers 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.
PubMed 18400714Fewtrell 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.
PubMed 12093949
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) Supplementation in Very Low Birth Weight Infants for The Prevention Retinopathy of Prematurity: Proposal for a Prospective Randomized Controlled Masked Clinical Trial With Lipidomic and Transcriptomic Analyses
- ClinicalTrials.gov ID
- NCT02486042
- Acronym / sponsor ID
- 140253
- Conditions
- Retinopathy of Prematurity
- Keywords
- ROP, Premature infant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- The Hartwell Foundation
- Study start
- Mar 2014
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 30 Jun 2015 (estimated)
- Results
- Posted 29 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (Standard Nutrition) | Active comparator | Dietary Supplement: Standard lipids (primarily omega-6 fatty acids)Infants in this group will receive standard lipids (predominantly Omega-6 fatty acids). |
| Omegaven | Experimental | Drug: OmegavenInfants in this group will receive lipid supplementation with omega-3 fatty acids. |
Who may qualify
- Ages
- Up to 7 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Infants born less than or equal to 30 weeks gestation or less than 1500 g at birth
Key exclusion criteria (2 listed)
- Patients with liver disease as tested by liver function tests (LFTs)
- ≤ 500 grams birthweight
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 |
|---|---|---|
| OmegavenAlso: Omega-3Infants will receive nutritional supplementation with omega-3 fatty acids (omegaven). | Drug | Omegaven |
| Standard lipids (primarily omega-6 fatty acids)Also: IntralipidInfants will receive nutritional supplementation with standard intralipid, composed primarily of omega-6 fatty acids. | Dietary supplement | Standard of Care (Standard Nutrition) |
Primary outcome
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T0
Time frame: T0 as defined in study protocol: prior to parental nutrition, within first three days of life
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T1
Time frame: T1 as defined in study protocol: 5 days after parenteral nutrition is started; grace period +/-3 days therefore total 2-8 days after parenteral nutrition started.
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3, PPAR-gamma, and STC-1 at T2
Time frame: T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk STC-1: stress response protein. Higher STC-1=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
Changes in mRNA Expression in Blood of STAT3 and PPAR-ɣ at T3
Time frame: T3 as defined in study protocol: Prior to discharge from hospital coinciding with time that ROP may be present, ≥35 weeks adjusted age.
Calculated using RNA extraction from blood, then quantitative polymerase chain reaction (qPCR) analysis. Biomarker significance: STAT3: role in hypoxia pathway leading to ROP (retinopathy of prematurity). Higher STAT3=greater ROP risk PPAR-ɣ: protective anti-angiogenic factor. Higher PPAR-ɣ=lower ROP risk Delta Ct meaning: qPCR gene expression analysis outputs Ct values for each genetic sample tested. A Ct value is the number of qPCR amplification cycles required for fluorescence, a proxy of gene expression, to cross a threshold. Lower Ct means less cycles of gene amplification needed for detectable fluorescence, therefore higher gene expression. Then target gene expression is calculated relative to a "housekeeping" control gene. Delta Ct=Ct(target gene)-Ct(control). Therefore, a HIGHER delta Ct value corresponds to a LOWER gene expression of the gene of interest relative to control.
3 secondary outcomes
Pilot Assay of Basic Fatty Acid Concentrations in Blood at Time T2
Time frame: T2 as defined in study protocol: 5 days after enteral nutrition full feeds have arrived; grace period +/-3 days therefore total 2-8 days after full enteral nutrition arrived.
Percentage of Eyes at the Furthest Stage of ROP Achieved
Time frame: approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)
Number of Patients Requiring Laser Treatment in Arm 1 Versus Arm 2
Time frame: approximately 31 to 40 weeks (adjusted age = gestation + post-natal age)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23364006Gould 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.
- Background: PubMed 7285840Clandinin 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.
- Background: PubMed 23935289Arsic 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.
- Background: PubMed 23963690Pawlik 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.
- Background: PubMed 17589522Connor 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.
- Background: PubMed 20634487Stahl 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.
- Background: PubMed 18708611Smith 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.
- Background: PubMed 15555528SanGiovanni 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.
- Background: PubMed 21199856Pawlik 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.
- Background: PubMed 23319354Klein 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.
- Background: PubMed 11236724Heird 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.
- Background: PubMed 11483801O'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.
- Individual participant dataSharing planned: No
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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.
Shira L. Robbins, M.D. principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omegaven and Standard lipids (primarily omega-6 fatty acids) in people with Retinopathy of Prematurity, run by University of California, San Diego 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 1 inclusion and 2 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: finished, as of the sponsor's last update on 29 Dec 2022. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in mRNA Expression in Blood of STAT3, PPAR-ɣ, and STC-1 at T0 (time frame: T0 as defined in study protocol: prior to parental nutrition, within first three days of life). The study lists 4 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 NCT02486042, which also lists 18 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 29 Dec 2022.