Intrauterine Growth RestrictionNCT04394910
Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)
A study testing Pomegranate Juice in people with Intrauterine Growth Restriction, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Infants diagnosed with intrauterine growth restriction are at increased risk for brain injury in the neonatal period, and eventually increased risk for adverse long-term neurodevelopmental outcomes. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Intrauterine Growth Restriction
- What is being tested?
- Pomegranate Juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2016to 26 Feb 2022
- Phase
- Interventional
- 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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Expecting mother with a fetal diagnosis of less than 5th percentile on the Doubilet fetal growth curve
Who cannot join
- Multiple congenital abnormalities
- Known fetal chromosomal disorder
- Maternal illicit drug or alcohol intake
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02215
About this study
Infants diagnosed with intrauterine growth restriction are at increased risk for brain injury in the neonatal period, and eventually increased risk for adverse long-term neurodevelopmental outcomes. This kind of growth restriction is often caused by long-term placental insufficiency leading to chronic lack of oxygen in the brain during development. Pomegranate juice is one of the highest polyphenol-containing dietary supplements commercially available. Previous studies have shown that pomegranate-derived polyphenols are potent neuroprotective antioxidants with no proven side effects. The investigators hypothesize that maternal dietary supplementation with pomegranate juice during the last trimester of pregnancy will reduce the effects of exogenous stimuli contributing to placental insufficiency, and will enhance brain growth and development in the IUGR population.
Read the detailed description
The current study seeks to investigate the impact of maternal dietary supplementation with pomegranate juice on placental morphology and on subsequent newborn brain development and function. A total of 99 consenting women carrying fetuses with a diagnosis of intrauterine growth restriction (IUGR) in the third trimester were randomized to one of two arms.
Treatment Group: Expecting mothers in this group will be randomized to consume 8oz of pomegranate juice daily. Participants will keep a daily diary documenting compliance with the regimen. Participants will continue daily intake until delivery.
Placebo group: Expecting mothers will be randomized to consume an 8oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. Participants will keep a diary of daily intake to help ensure compliance similar to the treatment group. Participants will continue to placebo until delivery.
Both groups: Maternal blood and urine samples will be collected prior to starting the juice regimen in order to establish baseline metabolite status. For the first 84 mothers enrolled, a fetal MRI was scheduled prior to beginning the juice regimen. Phase I participants will undergo two fetal echocardiograms: one before starting the juice regimen, and a second two weeks into the juice regimen to establish the safety of high polyphenol intake on fetal heart development. All women will be contacted on a weekly basis to assess compliance. At the time of delivery, maternal blood and urine, and cord blood will be collected and sent for analysis to test for the presence of dimethylellagic acid glucuronide (DMEAG) and urolithin A glucuronide (UAG), polyphenic components of pomegranate juice. Placental material will be sent for formal pathological exam.
If clinically stable, MRI will be undertaken without sedation at term equivalent (38-41 weeks CGA). Infants will undergo testing of cognitive, gross and fine motor, and speech skills at around 2 years of age.
- Conditions
- Intrauterine Growth Restriction
- Being tested
- Pomegranate Juice, Placebo Juice
- Medical subject headings
- Fetal Growth Retardation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pomegranate JuiceDietary supplement
Placebo JuiceDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Pomegranate Juice | Experimental | Dietary supplementation with 8 oz. commercially-available pomegranate juice consumed daily. Receives: Dietary Supplement: Pomegranate Juice |
| Placebo Juice | Placebo comparator | Dietary supplementation with 8 oz. placebo juice (identical to pomegranate juice but lacking polyphenols) consumed daily. Receives: Dietary Supplement: Placebo Juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant brain injury assessed on term-equivalent brain magnetic resonance image (MRI) using the Kidokoro injury scoring system.
The Kidokoro scale is a comprehensive, objective scoring system for classifying the nature and extent of neonatal brain injury on MRI (Kidokoro et al. American Journal of Neuroradiology. 2013; 34(11):2208-14).
Measured: One time occurrence at birth or term-equivalent age if infant is born preterm.
Total and regional infant brain volumes assessed on term equivalent brain MRI using MANTiS.
MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation) describes neonate-specific brain tissue segmentation into 8 categories using Statistical Parametric Mapping (SPM) software (Beare et al. Frontiers in Neuroinformatics. 2016;10:12).
Measured: One time occurrence at birth or term-equivalent age if infant is born preterm.
Diffusion tensor imaging measures of fractional anisotropy (FA), and mean (MD), radial (RD), and axial (AD) diffusivity from infant term equivalent brain MRI.
FA, MD, RD, and AD will be measured from a diffusion-weighted sequence on brain MRI.
Measured: One time occurrence at birth or term-equivalent age if infant is born preterm.
Secondary outcomes (2)
Cognitive, motor, and language neurodevelopment scores on the Bayley III exam.
The Bayley Scores of Infant and Toddler Development (Edition III) is a comprehensive examination tool used to assess neurodevelopment in infants and toddlers up to 42 months.
Measured: The Bayley III exam will be administered at a one-time visit scheduled between 18-36 months.
Maternal compliance with juice regimen.
Maternal compliance with the assigned juice regimen is assessed by participant logbook record and assessment of change in polyphenols (urolithin A and dimethylellagic glucuronide concentration, ng/mL) in maternal urine and blood at enrollment and in maternal urine, blood and cord blood at the time of delivery.
Measured: Comparison of one pre-juice regimen UA and DMEAG concentration measurement (ng/mL) to one post-juice regimen blood and urine concentration measurement (ng/mL) collected at the time of delivery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2020
- Study start16 Jan 2016
- Primary completion1 Jan 2022
- Study completion26 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intrauterine Growth RestrictionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles, POM Wonderful LLC
- Responsible party
- Principal investigator, Terrie Inder, Brigham and Women's Hospital
- Investigators
- Terrie E Inder, MD, MBChB, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04394910
- Sponsor's protocol ID
- 2014P000870
- Status last verified
- Jul 2023
- First submitted
- 11 May 2020
- Last updated
- 6 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) cannot be shared publicly because the investigators had not previously sought Institutional Review Board (IRB) approval for public sharing of participant data as part of the informed consent process. However, the investigators will gladly share with any investigator the de-identified minimal raw data set needed to replicate the study upon request.
Publications
Ross MM, Cherkerzian S, Mikulis ND, Turner D, Robinson J, Inder TE, Matthews LG. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021 Feb 11;11(1):3569. doi: 10.1038/s41598-021-82144-0.
PubMed 33574371
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)
- ClinicalTrials.gov ID
- NCT04394910
- Acronym / sponsor ID
- 2014P000870
- Conditions
- Intrauterine Growth Restriction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, POM Wonderful LLC
- Study start
- 16 Jan 2016 (actual)
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 26 Feb 2022 (actual)
- First posted
- 20 May 2020 (actual)
- 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.
Infants diagnosed with intrauterine growth restriction are at increased risk for brain injury in the neonatal period, and eventually increased risk for adverse long-term neurodevelopmental outcomes. This kind of growth restriction is often caused by long-term placental insufficiency leading to chronic lack of oxygen in the brain during development. Pomegranate juice is one of the highest polyphenol-containing dietary supplements commercially available. Previous studies have shown that pomegranate-derived polyphenols are potent neuroprotective antioxidants with no proven side effects. The investigators hypothesize that maternal dietary supplementation with pomegranate juice during the last trimester of pregnancy will reduce the effects of exogenous stimuli contributing to placental insufficiency, and will enhance brain growth and development in the IUGR population.
Detailed description
The current study seeks to investigate the impact of maternal dietary supplementation with pomegranate juice on placental morphology and on subsequent newborn brain development and function. A total of 99 consenting women carrying fetuses with a diagnosis of intrauterine growth restriction (IUGR) in the third trimester were randomized to one of two arms.
Treatment Group: Expecting mothers in this group will be randomized to consume 8oz of pomegranate juice daily. Participants will keep a daily diary documenting compliance with the regimen. Participants will continue daily intake until delivery.
Placebo group: Expecting mothers will be randomized to consume an 8oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. Participants will keep a diary of daily intake to help ensure compliance similar to the treatment group. Participants will continue to placebo until delivery.
Both groups: Maternal blood and urine samples will be collected prior to starting the juice regimen in order to establish baseline metabolite status. For the first 84 mothers enrolled, a fetal MRI was scheduled prior to beginning the juice regimen. Phase I participants will undergo two fetal echocardiograms: one before starting the juice regimen, and a second two weeks into the juice regimen to establish the safety of high polyphenol intake on fetal heart development. All women will be contacted on a weekly basis to assess compliance. At the time of delivery, maternal blood and urine, and cord blood will be collected and sent for analysis to test for the presence of dimethylellagic acid glucuronide (DMEAG) and urolithin A glucuronide (UAG), polyphenic components of pomegranate juice. Placental material will be sent for formal pathological exam.
If clinically stable, MRI will be undertaken without sedation at term equivalent (38-41 weeks CGA). Infants will undergo testing of cognitive, gross and fine motor, and speech skills at around 2 years of age.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pomegranate Juice | Experimental | Dietary Supplement: Pomegranate JuiceDietary supplementation with 8 oz. commercially-available pomegranate juice consumed daily. |
| Placebo Juice | Placebo comparator | Dietary Supplement: Placebo JuiceDietary supplementation with 8 oz. placebo juice (identical to pomegranate juice but lacking polyphenols) consumed daily. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Expecting mother with a fetal diagnosis of less than 5th percentile on the Doubilet fetal growth curve
Key exclusion criteria (3 listed)
- Multiple congenital abnormalities
- Known fetal chromosomal disorder
- Maternal illicit drug or alcohol intake
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 |
|---|---|---|
| Pomegranate Juice | Dietary supplement | Pomegranate Juice |
| Placebo Juice | Dietary supplement | Placebo Juice |
Primary outcome
Infant brain injury assessed on term-equivalent brain magnetic resonance image (MRI) using the Kidokoro injury scoring system.
Time frame: One time occurrence at birth or term-equivalent age if infant is born preterm.
The Kidokoro scale is a comprehensive, objective scoring system for classifying the nature and extent of neonatal brain injury on MRI (Kidokoro et al. American Journal of Neuroradiology. 2013; 34(11):2208-14).
Total and regional infant brain volumes assessed on term equivalent brain MRI using MANTiS.
Time frame: One time occurrence at birth or term-equivalent age if infant is born preterm.
MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation) describes neonate-specific brain tissue segmentation into 8 categories using Statistical Parametric Mapping (SPM) software (Beare et al. Frontiers in Neuroinformatics. 2016;10:12).
Diffusion tensor imaging measures of fractional anisotropy (FA), and mean (MD), radial (RD), and axial (AD) diffusivity from infant term equivalent brain MRI.
Time frame: One time occurrence at birth or term-equivalent age if infant is born preterm.
FA, MD, RD, and AD will be measured from a diffusion-weighted sequence on brain MRI.
2 secondary outcomes
Cognitive, motor, and language neurodevelopment scores on the Bayley III exam.
Time frame: The Bayley III exam will be administered at a one-time visit scheduled between 18-36 months.
Maternal compliance with juice regimen.
Time frame: Comparison of one pre-juice regimen UA and DMEAG concentration measurement (ng/mL) to one post-juice regimen blood and urine concentration measurement (ng/mL) collected at the time of delivery.
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 6 Jul 2023.
- Derived from this study: PubMed 33574371Ross MM, Cherkerzian S, Mikulis ND, Turner D, Robinson J, Inder TE, Matthews LG. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021 Feb 11;11(1):3569. doi: 10.1038/s41598-021-82144-0.
- Individual participant dataSharing planned: No. Individual participant data (IPD) cannot be shared publicly because the investigators had not previously sought Institutional Review Board (IRB) approval for public sharing of participant data as part of the informed consent process. However, the investigators will gladly share with any investigator the de-identified minimal raw data set needed to replicate the study upon request.
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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.
Terrie E Inder, MD, MBChB principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pomegranate Juice in people with Intrauterine Growth Restriction, run by Brigham and Women's Hospital 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 3 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 6 Jul 2023. 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?
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?
Infant brain injury assessed on term-equivalent brain magnetic resonance image (MRI) using the Kidokoro injury scoring system. (time frame: One time occurrence at birth or term-equivalent age if infant is born preterm.). The study lists 3 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 NCT04394910, which also lists 1 linked publication.
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 6 Jul 2023.