Multi-Center Study to Determine the Role of Fatty Acids in Serum in Preventing Retinopathy of Prematurity (MDM)

NCT03201588 | Completed DMC

• 1 other identifier: 303-11
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 3

Brief Summary

The study is a Randomized Intervention, Multi-Center Study to Determine the Role of Fatty Acids in Serum and Breast Milk in preventing Retinopathy of Prematurity Subjects who meet all inclusion and none of the exclusion criteria will be enrolled into the study. Upon entry into the study, subjects will be randomized and given a unique subject number. A randomized intervention study of 105+105 (number based on power analysis regarding up to date ROP frequency, see 5.1 and 11.1) infants without major malformations born with a gestational age less than 28 weeks + 0 days will be performed.

Conditions

Ophthalmological Disorder

Keywords

Retinopathy of Prematurity

Outcome Measures

Primary Outcomes (1)

• Investigate whether enteral administration of AA and DHA in addition to commonly used regimes with parenteral olive based lipid emulsion (Clinoleic) compared to Clinoleic alone prevents the sight threatening disease Retinopathy of Prematurity (ROP).

  Fatty Acids content (AA/DHA) in children with Retinopathy of Prematurity, change from baseline to 40 weeks postmenstrual weeks. Analyses of phospholipids witch can be done on small amount of blood, is relatively intensitive to short term fluctuations in intake and mirror the composition of many membranes in the body. The analyses will be made by using gas-liquid-chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids concerned.

  When the retina is fully vascularised, i.e approximately 40 postmenstrual weeks.

Secondary Outcomes (7)

• Postnatal serum fatty acid composition in preterm infants with and without AA:DHA supplementation.

  at 0h, 72h, day7, day 14, every other week until postmenstrual age 29 week and thereafter 30, 32, 34, 36 and 40 weeks postmenstrual age

• Postnatal brain development, as assessed by Magnetic Resonance Imaging (MRI)

  at 40 weeks postmenstrual age and at 2.0 y corrected age and 5.5 y uncorrected age.

• Outcome in p-glucose

  at 0h, 72h, day7, day 14, every other week until postmenstrual age 29 week and thereafter at 30, 32, 34, 36 and 40 weeks postmenstrual age.

• Outcome in weight in kilograms.

  at day 0, 7, 14, 21 and thereafter every week up to 40 weeks postmenstrual age

• Outcome in head circumference in centimeters.

  at day 0, 7, 14, 21 and thereafter every week up to 40 weeks postmenstrual age

Study Arms (2)

Formulaid

EXPERIMENTAL

Formulaid 2:1 Arachidonic acid/Docosahexaenoic acid (AA/DHA). Enteral supplement of AA (0,1-1ml) (100mg(kg/day) and DHA (50mg/kg/day) from birth to 40 weeks postmenstrual age in addition to conventional parenteral fatty acid treatment with Clinoleic

Dietary Supplement: Formulaid

Clinoleic

NO INTERVENTION

Sterile fat emulsion \[containing a mixture of refined olive oil (approximately 80%) and refined soya oil (approximately 20%)\] 200 g, egg lecithin (purified egg phospholipids) 12 g, glycerol 22.5 g, sodium oleate 0.3 g and Water for Injections to 1,000 mL (final pH between 6.0-8.0). One of the active ingredients, soya oil, contains ascorbyl palmitate as an antioxidant (free radical scavenger), in the concentration of 0.15 mg/g of oil.

Interventions

Formulaid DIETARY_SUPPLEMENT

Arachidonic acids (AA) Docosahexaenoic Acids(DHA) 2:1

Formulaid

Eligibility Criteria

• Age: 22 Weeks - 28 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from parents/guardians;
• Subject must be born before 28 weeks of gestation

You may not qualify if:

• Subjects presenting with any of the following will be excluded from the study:
• Detectable clinical gross malformation;
• Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the investigator's opinion;
• Clinically significant neuropathy, nephropathy, retinopathy, or other micro or macrovascular disease requiring treatment, according to the investigator's opinion
• Any other condition or therapy that, in the investigator's opinion, may pose a risk to the subject or interfere with the subject's ability to be compliant with this protocol or interfere with interpretation of results.

Sponsors & Collaborators

• Göteborg University: lead
• The Swedish Research Council: collaborator

Study Sites (3)

Queen Silvias Childrens Hospital

Gothenburg, 41650, Sweden

Location

Skanes Universitetssjukhus

Lund, Sweden

Location

KI

Stockholm, 14157, Sweden

Location

Related Publications (7)

• Hellstrom W, Lundgren P, Nilsson AK, Nilsson S, Hard AL, Sjobom U, Lofqvist C, Bjorkman-Burtscher IM, Wackernagel D, Hansen-Pupp I, Smith LE, Hallberg B, Savman K, Ley D, Hellstrom A, Heckemann RA. Effect of enteral arachidonic acid and docosahexaenoic acid supplementation on brain volumes at term in preterm infants: a secondary outcome analysis of a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2026 Jan 19:fetalneonatal-2024-328292. doi: 10.1136/archdischild-2024-328292. Online ahead of print.

  PMID: 41554627 DERIVED

• Lundgren P, Danielsson H, Panwar MB, Alvez MB, Pivodic A, Zhong W, Brusselaers N, Wackernagel D, Sjobom U, Savman K, Pupp IH, Ley D, Klevebro S, Nilsson AK, Fu Z, Smith LEH, Uhlen M, Hellstrom A. Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial. JAMA Ophthalmol. 2026 Jan 8:e255594. doi: 10.1001/jamaophthalmol.2025.5594. Online ahead of print.

  PMID: 41505112 DERIVED

• Klevebro S, Kebede Merid S, Sjobom U, Zhong W, Danielsson H, Wackernagel D, Hansen-Pupp I, Ley D, Savman K, Uhlen M, Smith LEH, Hellstrom A, Nilsson AK. Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants. Clin Nutr. 2024 May;43(5):1162-1170. doi: 10.1016/j.clnu.2024.03.031. Epub 2024 Apr 3.

  PMID: 38603973 DERIVED

• Sjobom U, Andersson MX, Pivodic A, Lund AM, Vanpee M, Hansen-Pupp I, Ley D, Wackernagel D, Savman K, Smith LEH, Lofqvist C, Hellstrom A, Nilsson AK. Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial. Clin Nutr. 2023 Jun;42(6):962-971. doi: 10.1016/j.clnu.2023.04.020. Epub 2023 Apr 17.

  PMID: 37120902 DERIVED

• Pivodic A, Johansson H, Smith LE, Lofqvist C, Albertsson-Wikland K, Nilsson S, Hellstrom A. Evaluation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) in a randomised controlled trial aiming for prevention of severe ROP: a substudy of the Mega Donna Mega trial. BMJ Open Ophthalmol. 2022 Apr 8;7(1):e000923. doi: 10.1136/bmjophth-2021-000923. eCollection 2022.

  PMID: 35495419 DERIVED

• Hortensius LM, Hellstrom W, Savman K, Heckemann RA, Bjorkman-Burtscher IM, Groenendaal F, Andersson MX, Nilsson AK, Tataranno ML, van Elburg RM, Hellstrom A, Benders MJNL. Serum docosahexaenoic acid levels are associated with brain volumes in extremely preterm born infants. Pediatr Res. 2021 Dec;90(6):1177-1185. doi: 10.1038/s41390-021-01645-w. Epub 2021 Aug 14.

  PMID: 34392310 DERIVED

• Hellstrom A, Nilsson AK, Wackernagel D, Pivodic A, Vanpee M, Sjobom U, Hellgren G, Hallberg B, Domellof M, Klevebro S, Hellstrom W, Andersson M, Lund AM, Lofqvist C, Elfvin A, Savman K, Hansen-Pupp I, Hard AL, Smith LEH, Ley D. Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr. 2021 Apr 1;175(4):359-367. doi: 10.1001/jamapediatrics.2020.5653.

  PMID: 33523106 DERIVED

MeSH Terms

Conditions

Eye Diseases; Retinopathy of Prematurity

Condition Hierarchy (Ancestors)

Retinal Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ann ca Hellstrom, Professor

  Göteborg University

  PRINCIPAL INVESTIGATOR

• David Ley, Professor

  University of Lund

  PRINCIPAL INVESTIGATOR

• Boubou Hallberg, MD,PhD

  University of Karolinska

  PRINCIPAL INVESTIGATOR

• Karin Savman, MD, PhD

  Göteborg University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized intervention study of 105+105 (number based on power analysis regarding up to date ROP frequency, see 5.1 and 11.1) infants without major malformations born with a gestational age less than 28 weeks + 0 days will be performed.

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 28, 2017
• Study Start: December 15, 2016
• Primary Completion: November 15, 2019
• Study Completion: December 13, 2019
• Last Updated: December 18, 2019

Record last verified: 2019-12

Locations

SE (3)