Retinopathy of PrematurityPhase 3DonnaMegaNCT02760472
A Fatty Acids Study in Preventing Retinopathy of Prematurity
A Phase 3 study testing SMOFlipid and Clinoleic in people with Retinopathy of Prematurity, run by Carola Pfeiffer-Mosesson.
Trial summary
Most fatty acids, important for development and especially the Omega-3 fatty acids for the brain development are transferred in the third trimester with means that in the premature infant this transport via the placenta is interrupted and the infant is dependent on the concentrations in breast milk which vary… Read more about this study
- Who is it for?
- Ages 23 to 28 weeks
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- SMOFlipid and Clinoleic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- No sites listed yet
- Study dates
- Mar 2013to Sep 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 23 to 28 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed informed consent from parents/guardians;
- Subject must be below 28 weeks of gestation
Who cannot join
- Detectable clinical gross malformation;
- Known or suspected chromosomal abnormality, genetic disorder, or syn-drome, 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.
- Bleeding disorder.
About this study
Official title: A Randomised Intervention Single Center Study to Determine the Role of Fatty Acids in Serum in Preventing Retinopathy of Prematurity
Most fatty acids, important for development and especially the Omega-3 fatty acids for the brain development are transferred in the third trimester with means that in the premature infant this transport via the placenta is interrupted and the infant is dependent on the concentrations in breast milk which vary depending on the mother's diet and her stores. It has even been suggested that low Omega-3 would be a cause of premature delivery. Many countries have much higher levels of Omega-3 fatty acids in breast milk than found in Sweden and breast milk substitutions are generally now supplemented with the Long Chained Poly Unsaturated Fatty Acids (LCPUFA). Therefore the supplementation to be given can not be seen to give any risks for the infant. On the contrary, several studies have shown that mother who eat equal to or less than twice fish a week during pregnancy give birth to infants with impaired development.
Low Omega-3 levels in premature infants between gestational ages of 23 and 40 weeks can be one reason for Retinopathy of Prematurity (ROP) development. Restoration of Omega-3, Dokosahexaenacid (DHA) and Eikosapentaenacid (EPA) to normal in utero levels may prevent ROP by allowing normal vessel growth and survival. An increase of Omega-3 levels bringing levels to within physiological range may prevent development of ROP.
Read the detailed description
The study is a Randomised Intervention, Single-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 randomised intervention study of 45+45 infants without major malformations born with a gestational age less than 28 weeks + 0 days will be performed.
Randomization of the patients to either:
- Conventional fatty acid supplementation regime with Clinoleic (with Vitalipid infant and Soluvit supplementation) to the preterm infant Or
- SMOFlipid, (soybean oil, medium chain triglycerides, olive oil and fish oil),(with Vitalipid infant and Soluvit supplementation), where the quotient of Omega 6:3 is 2.5:1 in order to mimic the physiologic relation of fatty acids in cord blood from birth, to the preterm infant.
Thus there is one group of infants (n=45) that will receive Omega-3 in the fatty acid supplementation.
The time on parenteral nutrition and the amount of fatty acids given will be according to clinical routines.
The randomization of the patients will be performed by the controller of the study. Randomization will be in blocks with 10 children in each block.
Data collection
After the investigators have received informed consent from the parents/guardians, blood samples 0.2 ml from the child will be taken according to present clinical practice at if possible from cord (2ml) and at days 0, 7, 14, 28 and in postmenstrual weeks 32, 36 and 40. Blood samples from the mothers for Fatty Acids analyses will be taken after birth, day 7 and at gestational weeks 36 and 40. At the same time (except from day 1), breast milk samples are taken. Length in cm, weight in gram and head circumference in cm are measured weekly.
Screening for ROP will be performed, at least once a week, according to clinical routines using a specific protocol.
The investigators intend to analyze the content of phospholipids which can be done on small amounts of blood, is relatively insensitive to short term fluctuations in intake and mirror the composition of many membranes in the body. The analyses will be made using gas-liquid chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids concerned.
- Conditions
- Retinopathy of Prematurity
- Being tested
- SMOFlipid, Clinoleic
- Keywords
- Retinopathy of Prematurity, Preterm, Fatty acids
- 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.
SMOFlipidDrug
Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity
ClinoleicDrug
Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity
| Study group | Role | What they receive |
|---|---|---|
| Clinoleic | Active comparator | Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity Receives: Drug: Clinoleic |
| SMOFlipid | Experimental | Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity Receives: Drug: SMOFlipid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retinopathy of Prematurity
We intend to analyze the content of Fatty Acids and correlate to Retinopathy of Prematurity development and interventional treatment. Analyze of phospholipids can be done on small amounts of blood, is relatively insensitive to short term fluctuations in intake and mirror the composition of many membranes in the body. The analyses will be made using gas-liquid chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids concerned.
Measured: When the retina is fully vascularised,i.e. at approximately 40 postmenstrual weeks.
Secondary outcomes (4)
Brain Growth
Cranial ultrasound will be performed according to clinical praxis. MRI of the brain will be performed at 40 weeks postmenstrual age (PMA) and correlated to interventional treatment.
Measured: At 40 postmenstrual weeks and at 2.5 and 6 years.
Length in cm
Length in cm given in absolute values and in standard deviation scores, at 40 weeks postmenstrual age (PMA) and at 2.5 and 6 years will be correlated to interventional treatment.
Measured: At 40 postmenstrual weeks and at 2.5 and 6 years.
Weight in gram
Weight in gram given in absolute values and in standard deviation scores, at 40 weeks postmenstrual age (PMA) and at 2.5 and 6 years will be correlated to interventional treatment.
Measured: At 40 postmenstrual weeks and at 2.5 and 6 years.
Head circumference in cm
Head circumference in cm given in absolute values and in standard deviation scores, at 40 weeks postmenstrual age (PMA) and at 2.5 and 6 years will be correlated to interventional treatment.
Measured: At 40 postmenstrual weeks and at 2.5 and 6 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2016 (estimated)
- Study startMar 2013
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carola Pfeiffer-Mosesson
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Carola Pfeiffer-Mosesson, Queen Silvia Children's Hospital, Gothenburg, Sweden
- Investigators
- Carola Pfeiffer-Mosesson, RN, Principal investigator, The Queen Silvia Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02760472
- Sponsor's protocol ID
- 2008-000046-31
- Other IDs
- 2008
- Acronym
- DonnaMega
- Status last verified
- Apr 2016
- First submitted
- 30 Mar 2016
- Last updated
- 3 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Cakir B, Hellstrom W, Tomita Y, Fu Z, Liegl R, Winberg A, Hansen-Pupp I, Ley D, Hellstrom A, Lofqvist C, Smith LE. IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants. JCI Insight. 2020 Oct 2;5(19):e140363. doi: 10.1172/jci.insight.140363.
PubMed 33004691Nilsson AK, Pedersen A, Malmodin D, Lund AM, Hellgren G, Lofqvist C, Pupp IH, Hellstrom A. Serum choline in extremely preterm infants declines with increasing parenteral nutrition. Eur J Nutr. 2021 Mar;60(2):1081-1089. doi: 10.1007/s00394-020-02312-2. Epub 2020 Jun 25.
PubMed 32588218Lundgren P, Hellgren G, Pivodic A, Savman K, Smith LEH, Hellstrom A. Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity. Pediatr Res. 2019 Aug;86(2):276-282. doi: 10.1038/s41390-018-0186-6. Epub 2018 Sep 18.
PubMed 30297879Lofqvist CA, Najm S, Hellgren G, Engstrom E, Savman K, Nilsson AK, Andersson MX, Hard AL, Smith LEH, Hellstrom A. Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2018 Mar 1;136(3):271-277. doi: 10.1001/jamaophthalmol.2017.6658.
PubMed 29423508
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Intervention Single Center Study to Determine the Role of Fatty Acids in Serum in Preventing Retinopathy of Prematurity
- ClinicalTrials.gov ID
- NCT02760472
- Acronym / sponsor ID
- DonnaMega / 2008-000046-31
- Conditions
- Retinopathy of Prematurity
- Keywords
- Retinopathy of Prematurity, Preterm, Fatty acids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Carola Pfeiffer-MosessonUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 3 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Most fatty acids, important for development and especially the Omega-3 fatty acids for the brain development are transferred in the third trimester with means that in the premature infant this transport via the placenta is interrupted and the infant is dependent on the concentrations in breast milk which vary depending on the mother's diet and her stores. It has even been suggested that low Omega-3 would be a cause of premature delivery. Many countries have much higher levels of Omega-3 fatty acids in breast milk than found in Sweden and breast milk substitutions are generally now supplemented with the Long Chained Poly Unsaturated Fatty Acids (LCPUFA). Therefore the supplementation to be given can not be seen to give any risks for the infant. On the contrary, several studies have shown that mother who eat equal to or less than twice fish a week during pregnancy give birth to infants with impaired development.
Low Omega-3 levels in premature infants between gestational ages of 23 and 40 weeks can be one reason for Retinopathy of Prematurity (ROP) development. Restoration of Omega-3, Dokosahexaenacid (DHA) and Eikosapentaenacid (EPA) to normal in utero levels may prevent ROP by allowing normal vessel growth and survival. An increase of Omega-3 levels bringing levels to within physiological range may prevent development of ROP.
Detailed description
The study is a Randomised Intervention, Single-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 randomised intervention study of 45+45 infants without major malformations born with a gestational age less than 28 weeks + 0 days will be performed.
Randomization of the patients to either:
- Conventional fatty acid supplementation regime with Clinoleic (with Vitalipid infant and Soluvit supplementation) to the preterm infant Or
- SMOFlipid, (soybean oil, medium chain triglycerides, olive oil and fish oil),(with Vitalipid infant and Soluvit supplementation), where the quotient of Omega 6:3 is 2.5:1 in order to mimic the physiologic relation of fatty acids in cord blood from birth, to the preterm infant.
Thus there is one group of infants (n=45) that will receive Omega-3 in the fatty acid supplementation.
The time on parenteral nutrition and the amount of fatty acids given will be according to clinical routines.
The randomization of the patients will be performed by the controller of the study. Randomization will be in blocks with 10 children in each block.
Data collection
After the investigators have received informed consent from the parents/guardians, blood samples 0.2 ml from the child will be taken according to present clinical practice at if possible from cord (2ml) and at days 0, 7, 14, 28 and in postmenstrual weeks 32, 36 and 40. Blood samples from the mothers for Fatty Acids analyses will be taken after birth, day 7 and at gestational weeks 36 and 40. At the same time (except from day 1), breast milk samples are taken. Length in cm, weight in gram and head circumference in cm are measured weekly.
Screening for ROP will be performed, at least once a week, according to clinical routines using a specific protocol.
The investigators intend to analyze the content of phospholipids which can be done on small amounts of blood, is relatively insensitive to short term fluctuations in intake and mirror the composition of many membranes in the body. The analyses will be made using gas-liquid chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids concerned.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clinoleic | Active comparator | Drug: ClinoleicParenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity |
| SMOFlipid | Experimental | Drug: SMOFlipidParenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity |
Who may qualify
- Ages
- 23 to 28 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Signed informed consent from parents/guardians;
- Subject must be below 28 weeks of gestation
Key exclusion criteria (5 listed)
- Detectable clinical gross malformation;
- Known or suspected chromosomal abnormality, genetic disorder, or syn-drome, 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.
- Bleeding disorder.
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 |
|---|---|---|
| SMOFlipidParenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity | Drug | SMOFlipid |
| ClinoleicParenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity | Drug | Clinoleic |
Primary outcome
Retinopathy of Prematurity
Time frame: When the retina is fully vascularised,i.e. at approximately 40 postmenstrual weeks.
We intend to analyze the content of Fatty Acids and correlate to Retinopathy of Prematurity development and interventional treatment. Analyze of phospholipids can be done on small amounts of blood, is relatively insensitive to short term fluctuations in intake and mirror the composition of many membranes in the body. The analyses will be made using gas-liquid chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids concerned.
4 secondary outcomes
Brain Growth
Time frame: At 40 postmenstrual weeks and at 2.5 and 6 years.
Length in cm
Time frame: At 40 postmenstrual weeks and at 2.5 and 6 years.
Weight in gram
Time frame: At 40 postmenstrual weeks and at 2.5 and 6 years.
Head circumference in cm
Time frame: At 40 postmenstrual weeks and at 2.5 and 6 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2016.
- Derived from this study: PubMed 33004691Cakir B, Hellstrom W, Tomita Y, Fu Z, Liegl R, Winberg A, Hansen-Pupp I, Ley D, Hellstrom A, Lofqvist C, Smith LE. IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants. JCI Insight. 2020 Oct 2;5(19):e140363. doi: 10.1172/jci.insight.140363.
- Derived from this study: PubMed 32588218Nilsson AK, Pedersen A, Malmodin D, Lund AM, Hellgren G, Lofqvist C, Pupp IH, Hellstrom A. Serum choline in extremely preterm infants declines with increasing parenteral nutrition. Eur J Nutr. 2021 Mar;60(2):1081-1089. doi: 10.1007/s00394-020-02312-2. Epub 2020 Jun 25.
- Derived from this study: PubMed 30297879Lundgren P, Hellgren G, Pivodic A, Savman K, Smith LEH, Hellstrom A. Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity. Pediatr Res. 2019 Aug;86(2):276-282. doi: 10.1038/s41390-018-0186-6. Epub 2018 Sep 18.
- Derived from this study: PubMed 29423508Lofqvist CA, Najm S, Hellgren G, Engstrom E, Savman K, Nilsson AK, Andersson MX, Hard AL, Smith LEH, Hellstrom A. Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2018 Mar 1;136(3):271-277. doi: 10.1001/jamaophthalmol.2017.6658.
- HomepageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes
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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.
Carola Pfeiffer-Mosesson, RN principal investigator
The Queen Silvia Children's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SMOFlipid and Clinoleic in people with Retinopathy of Prematurity, run by Carola Pfeiffer-Mosesson.
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 2 inclusion and 5 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 3 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Retinopathy of Prematurity (time frame: When the retina is fully vascularised,i.e. at approximately 40 postmenstrual weeks.). 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 NCT02760472, which also lists 4 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 3 May 2016.