PrematurityNCT01908907
Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants
A study testing DHA oil in people with Prematurity, run by Sanford Health at 1 site in United States.
Trial summary
The purpose of this study is to understand if the "DHA gap" can be corrected by giving a daily dose of DHA oil to preterm babies. DHA is an essential omega-3 fatty acid, which means our body cannot make DHA. We have to take it in through our diet. Read more about this study
- Who is it for?
- Ages 24 to 33 weeksHealthy volunteers can take part
- Conditions the study is for
- Prematurity
- What is being tested?
- DHA oil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Feb 2014
- Phase
- Interventional
- 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 24 to 33 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Preterm infants between 24 and 33 6/7 weeks gestation
- must be less than or equal to 1 week of age
Who cannot join
- infants who are considered by the medical team to be non-viable
- infants with multiple or severe congenital anomalies such as gastroschisis, congenital chylothorax or other illnesses that do not allow a feeding tube to be placed or utilized at 7 days of age.
- term infants: who are born to mothers with diabetes or are small for gestational age (SGA-less than the 10th% for adjusted gestational age
- All families consented for this study will need to be able to read and write English
- Mother must be 18 years of age or older
- Taking Omegaven
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to understand if the "DHA gap" can be corrected by giving a daily dose of DHA oil to preterm babies.
DHA is an essential omega-3 fatty acid, which means our body cannot make DHA. We have to take it in through our diet. DHA is important for normal brain and eye health and it may also decrease inflammation. This is important for premature babies because they are at a greater risk for getting diseases related to inflammation, especially in their lungs, eyes and intestines. Since DHA is so important for normal growth, you will find DHA naturally in breast milk and it is now added to infant formula. But the amount in breast milk and infant formula is about half of what your infant should expect to get in the womb (about 13-29mg per day in breast milk vs. 50-75mg per day in the womb). Very premature babies are at an even greater disadvantage because they cannot always eat very much right away and that is the only way they can get essential fatty acids in their body. This means premature babies are getting less DHA than they would in the womb and then the "DHA gap" continues for a longer period of time. This gap also comes at a time when their brain is growing most rapidly and their bodies need it the most. This trial is designed to see if giving DHA, even before the baby can take food orally, will raise his/her DHA blood levels to those of normal term babies.
Read the detailed description
Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective is to develop a DHA supplementation strategy to overcome these barriers. This single-center, double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels will be analyzed at baseline, full feedings and near discharge in DHA or placebo supplemented preterm infants. Term peers will also have blood FA levels analyzed for comparison. Growth, feeding tolerance and adverse outcomes (NEC, intraventricular hemorrhage (IVH), thrombocytopenia, sepsis) will be evaluated. Study progress and safety will be monitored by an external Data Safety Monitoring Board (DSMB). Overall, the study aims to determine if daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.
- Conditions
- Prematurity
- Being tested
- DHA oil, (MCT) Control oil
- Keywords
- Premature Infants, DHA(docosahexaenoic acid), DHA deficit
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHA oilDietary supplement
Therapy Group:DHA oil administered at 50 mg/d (0.18ml) as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
(MCT) Control oilDietary supplement
Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one.
| Study group | Role | What they receive |
|---|---|---|
| DHA oil | Active comparator | DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Receives: Dietary Supplement: DHA oil |
| (MCT) control oil | Placebo comparator | MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Receives: Dietary Supplement: (MCT) Control oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days to Reach Full Enteral Feedings and Days on Study Oil.
This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.
Measured: From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.
Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change
A linear mixed model was used to explore weight over time.
Measured: 30 days from birth
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Measured: At baseline (enrollment, < 1 week of age), full feedings, discharge
Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change
A linear mixed model was used to explore length over time.
Measured: 30 days from birth
Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference
A linear mixed model was used to explore head circumference over time.
Measured: 30 days from birth
Secondary outcomes (1)
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Measured: At baseline (enrollment, <1 week of age), full feedings and discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2013 (estimated)
- Study startOct 2012
- Primary completionFeb 2014
- Study completionFeb 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanford Health
- Sponsor type
- University, hospital or other
- Collaborators
- The Gerber Foundation
- Responsible party
- Sponsor
- Investigators
- Michelle L Baack, MD, Principal investigator, Sanford Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01908907
- Sponsor's protocol ID
- DHA Gap
- Status last verified
- Mar 2019
- First submitted
- 2 Jul 2013
- Last updated
- 21 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Individual participant data (IPD) will not be shared with other researchers. All data is de-identified for review by DSMB or others.
Publications
Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants. Lipids. 2016 Apr;51(4):423-33. doi: 10.1007/s11745-016-4130-4. Epub 2016 Feb 4.
PubMed 26846324Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels? Prostaglandins Leukot Essent Fatty Acids. 2015 Sep;100:5-11. doi: 10.1016/j.plefa.2015.05.003. Epub 2015 Jun 17.
PubMed 26205427
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bridging the Docosahexaenoic Acid (DHA) Gap: The Effects of Omega-3 Fatty Acid Supplementation in Premature Infants
- ClinicalTrials.gov ID
- NCT01908907
- Acronym / sponsor ID
- DHA Gap
- Conditions
- Prematurity
- Keywords
- Premature Infants, DHA(docosahexaenoic acid), DHA deficit
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Sanford HealthUniversity, hospital or other
- Collaborators
- The Gerber Foundation
- Study start
- Oct 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 26 Jul 2013 (estimated)
- Results
- Posted 2 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to understand if the "DHA gap" can be corrected by giving a daily dose of DHA oil to preterm babies.
DHA is an essential omega-3 fatty acid, which means our body cannot make DHA. We have to take it in through our diet. DHA is important for normal brain and eye health and it may also decrease inflammation. This is important for premature babies because they are at a greater risk for getting diseases related to inflammation, especially in their lungs, eyes and intestines. Since DHA is so important for normal growth, you will find DHA naturally in breast milk and it is now added to infant formula. But the amount in breast milk and infant formula is about half of what your infant should expect to get in the womb (about 13-29mg per day in breast milk vs. 50-75mg per day in the womb). Very premature babies are at an even greater disadvantage because they cannot always eat very much right away and that is the only way they can get essential fatty acids in their body. This means premature babies are getting less DHA than they would in the womb and then the "DHA gap" continues for a longer period of time. This gap also comes at a time when their brain is growing most rapidly and their bodies need it the most. This trial is designed to see if giving DHA, even before the baby can take food orally, will raise his/her DHA blood levels to those of normal term babies.
Detailed description
Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective is to develop a DHA supplementation strategy to overcome these barriers. This single-center, double-blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels will be analyzed at baseline, full feedings and near discharge in DHA or placebo supplemented preterm infants. Term peers will also have blood FA levels analyzed for comparison. Growth, feeding tolerance and adverse outcomes (NEC, intraventricular hemorrhage (IVH), thrombocytopenia, sepsis) will be evaluated. Study progress and safety will be monitored by an external Data Safety Monitoring Board (DSMB). Overall, the study aims to determine if daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DHA oil | Active comparator | Dietary Supplement: DHA oilDHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. |
| (MCT) control oil | Placebo comparator | Dietary Supplement: (MCT) Control oilMCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. |
Who may qualify
- Ages
- 24 to 33 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Preterm infants between 24 and 33 6/7 weeks gestation
- must be less than or equal to 1 week of age
Key exclusion criteria (6 listed)
- infants who are considered by the medical team to be non-viable
- infants with multiple or severe congenital anomalies such as gastroschisis, congenital chylothorax or other illnesses that do not allow a feeding tube to be placed or utilized at 7 days of age.
- term infants: who are born to mothers with diabetes or are small for gestational age (SGA-less than the 10th% for adjusted gestational age
- All families consented for this study will need to be able to read and write English
- Mother must be 18 years of age or older
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 |
|---|---|---|
| DHA oilTherapy Group:DHA oil administered at 50 mg/d (0.18ml) as an oil emulsion enterally with feedings or by gavage tube if the infant has one. | Dietary supplement | DHA oil |
| (MCT) Control oilPlacebo Group:MCT oil administered at 0.18 ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. | Dietary supplement | (MCT) control oil |
Primary outcome
Days to Reach Full Enteral Feedings and Days on Study Oil.
Time frame: From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.
This study was designed to determine feasibility and tolerability of enteral DHA supplementation, but was not intended to determine the effects of DHA on health related outcomes. Tolerability was measured by days to reach full enteral feedings, days on study oil, GA at completion of the study and postnatal growth. The days to reach full enteral feedings was defined as enteral intake of 100kcal/kg/d. Safety and tolerability was closely monitored under the oversight of an independent DSMB.
Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change
Time frame: 30 days from birth
A linear mixed model was used to explore weight over time.
Long Chain Polyunsaturated Fatty Acid (LCPUFA) Levels - Docosahexaenoic Acid (DHA) Levels in Whole Blood
Time frame: At baseline (enrollment, < 1 week of age), full feedings, discharge
Linear mixed models were also used to examine the association between each FA of interest and treatment group over time. Since only three time points were available for FA measurement, only a random intercept was included in the models. For these models, the random effect for multiples was again found to be not needed and removed. Primary outcome variables for this analysis included LNA, ALA, ARA and DHA. Only early/late preterm status was included in the model as a covariate since this was a stratification variable. Continuous dependent variables were transformed using the natural logarithm as needed to meet the assumptions of the regression model (this included LNA and ALA).
Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change
Time frame: 30 days from birth
A linear mixed model was used to explore length over time.
Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference
Time frame: 30 days from birth
A linear mixed model was used to explore head circumference over time.
1 secondary outcome
LCPUFA Levels - Arachidonic Acid (ARA) in Whole Blood
Time frame: At baseline (enrollment, <1 week of age), full feedings and discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26846324Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants. Lipids. 2016 Apr;51(4):423-33. doi: 10.1007/s11745-016-4130-4. Epub 2016 Feb 4.
- Derived from this study: PubMed 26205427Baack ML, Puumala SE, Messier SE, Pritchett DK, Harris WS. What is the relationship between gestational age and docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels? Prostaglandins Leukot Essent Fatty Acids. 2015 Sep;100:5-11. doi: 10.1016/j.plefa.2015.05.003. Epub 2015 Jun 17.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared with other researchers. All data is de-identified for review by DSMB or others.
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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.
Michelle L Baack, MD principal investigator
Sanford Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DHA oil in people with Prematurity, run by Sanford Health 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 2 inclusion and 6 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 21 Mar 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2018). 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?
Days to Reach Full Enteral Feedings and Days on Study Oil. (time frame: From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days.). The study lists 5 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 NCT01908907, which also lists 2 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 21 Mar 2019.