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| Name | Class |
|---|---|
| The Gerber Foundation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| (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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DHA oil | Dietary 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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). | 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. | 30 days from birth |
| Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| LCPUFA Levels - Alpha-linolenic Acid (ALA) 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). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michelle L Baack, MD | Sanford Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanford Health USD | Sioux Falls | South Dakota | 57117 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26846324 | Derived | 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. | |
| 26205427 | Derived | Baack 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. |
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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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Preterm infants were between 24 and 33 6/7 weeks gestational age (GA) at birth. Adaptive enrollment was used to assure that infants <28 weeks GA were enrolled over the same time period as more commonly admitted preterm infants >28 weeks GA.
Ninety infants, less than or equal to one week of age, were recruited from the Sanford Health Boekelheide Neonatal Intensive Care Unit (NICU) between October 2012 and March 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | DHA Oil | DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml |
| FG001 | Medium Chain Triglyceride (MCT) Control Oil | MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Preterm infants less than one week of age and born between 24 and 33 6/7 week GA were randomized to receive 50mg/d of enteral DHA
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| ID | Title | Description |
|---|---|---|
| BG000 | DHA Supplemented | Preterm infants (31) randomized to receive 50mg/d of enteral DHA supplementation |
| BG001 | Placebo Supplemented | Preterm infants (29) randomized to receive placebo study oil |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. | Posted | Mean | Standard Deviation | days | From enrollment until the infant reaches full feed or is discharged from the NICU, whichever comes first, assessed up to 50 days. |
|
Monitored for 30 days after last dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DHA Oil | DHA oil administered 50 mg/d (0.18ml)as an oil emulsion enterally with feedings or by gavage tube if the infant has one. DHA oil administered at 50 mg/d (0.18ml) Or MCT oil administered at 0.18 ml |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchopulmonary Dysplasia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lora Black, Senior Director of Clinical Research | Sanford Health | 605-328-1368 | lora.black@sanfordhealth.org |
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| (MCT) Control oil | Dietary 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. |
|
A linear mixed model was used to explore head circumference over time. |
| 30 days from birth |
| At baseline (enrollment, <1 week of age), full feedings and discharge |
| Baseline (<1 week of age), full enteral feedings and discharge |
| LCPUFA Levels - Linoleic Acid (LNA) | 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). | Baseline, full feedings and discharge |
| BG002 | Total | Total of all reporting groups |
| weeks of GA |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | (MCT) Control Oil | MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion |
|
|
|
| Primary | Feasibility and Tolerability of Daily Enteral DHA Oil - Weight Change | A linear mixed model was used to explore weight over time. | Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU. | Posted | Mean | Standard Error | Grams per day | 30 days from birth |
|
|
|
|
| Primary | 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). | Posted | Mean | Standard Deviation | mol% (composition) of fat | At baseline (enrollment, < 1 week of age), full feedings, discharge |
|
|
|
| Primary | Feasibility and Tolerability of Daily Enteral DHA Oil - Length Change | A linear mixed model was used to explore length over time. | Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU. | Posted | Mean | Standard Error | Centimeters per day | 30 days from birth |
|
|
|
| Primary | Feasibility and Tolerability of Daily Enteral DHA Oil - Head Circumference | A linear mixed model was used to explore head circumference over time. | Comparison between preterm groups that received either DHA oil or MCT (placebo control) oil were made. They had DHA levels measured to be used as a reference population in our NICU. | Posted | Mean | Standard Error | Centimeters per day | 30 days from birth |
|
|
|
| Secondary | 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). | Posted | Mean | Standard Deviation | wt:wt% of total fat in sample | At baseline (enrollment, <1 week of age), full feedings and discharge |
|
|
|
| Other Pre-specified | LCPUFA Levels - Alpha-linolenic Acid (ALA) 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). | Posted | Mean | Standard Deviation | wt:wt% (composition) of total fat | Baseline (<1 week of age), full enteral feedings and discharge |
|
|
|
| Other Pre-specified | LCPUFA Levels - Linoleic Acid (LNA) | 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). | Posted | Mean | Standard Deviation | wt:wt% (composition) of fat in sample | Baseline, full feedings and discharge |
|
|
|
| 1 |
| 31 |
| 31 |
| 31 |
| EG001 | (MCT) Control Oil | MCT oil administered 0.18ml as an oil emulsion enterally with feedings or by gavage tube if the infant has one. Placebo Group:MCT oil administered at 0.18 ml as an oil emulsion | 0 | 29 | 29 | 29 |
| Death | General disorders | Non-systematic Assessment |
|
| Sepsis (Grade 4) | Infections and infestations | Systematic Assessment |
|
| Retinopathy of Prematurity | Eye disorders | Systematic Assessment |
|
| Gastro-esophageal Reflux Disease | Gastrointestinal disorders | Systematic Assessment |
|
| Milk Soy Protein Intolerance | Metabolism and nutrition disorders | Systematic Assessment |
|
| Intraventricular Hemorrhage | Nervous system disorders | Systematic Assessment |
|
| Periventricular Leukomalacia | Cardiac disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Apnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other Blood and lymphatic disorders | Blood and lymphatic system disorders | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | Systematic Assessment |
|
| Other Cardiac Disorders | Cardiac disorders | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | Systematic Assessment |
|
| Congenital heart defect | Cardiac disorders | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Dysfunctional bottling/swallowing | Gastrointestinal disorders | Systematic Assessment |
|
| Other Endocrine Disorders | Endocrine disorders | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | Systematic Assessment |
|
| Gastrointestinal Disorder NOS | Gastrointestinal disorders | Systematic Assessment |
|
| Other General Disorder | General disorders | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other Infections and Infestations | Infections and infestations | Systematic Assessment |
|
| Irritability | Psychiatric disorders | Systematic Assessment |
|
| Meningitis | Infections and infestations | Systematic Assessment |
|
| Other Metabolism and Nutrition Disorders | Metabolism and nutrition disorders | Systematic Assessment |
|
| Other Musculoskeletal Disorders | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Patent Ductus Arteriosus | Cardiac disorders | Systematic Assessment |
|
| Periodic Breathing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Physiologic murmur | Cardiac disorders | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Other Renal and Urinary Disorders | Renal and urinary disorders | Systematic Assessment |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Other Respiratory Disorder | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Scoliosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Other Skin Disorders | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Thromboembolic Event | Vascular disorders | Systematic Assessment |
|
| Tracheitis | Infections and infestations | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
|
| Urinary Tract Obstruction | Renal and urinary disorders | Systematic Assessment |
|
| Other Vascular Disorders | Vascular disorders | Systematic Assessment |
|
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| D000091642 | Urogenital Diseases |
| Superiority or Other |
| Discharge |
|
| Discharge |
|
| Discharge |
|
| Discharge |
|