Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04394910
Recruitment Status : Active, not recruiting
First Posted : May 20, 2020
Last Update Posted : September 16, 2020
Sponsor:
Collaborators:
University of California, Los Angeles
POM Wonderful LLC
Information provided by (Responsible Party):
Terrie Inder, Brigham and Women's Hospital

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Intrauterine Growth Restriction Dietary Supplement: Pomegranate Juice Dietary Supplement: Placebo Juice Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of Antioxidant Juice Intake on Brain Injury and Placental Pathology in Infants With Intrauterine Growth Restriction (IUGR)
Actual Study Start Date : January 16, 2016
Actual Primary Completion Date : January 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antioxidants

Arm Intervention/treatment
Experimental: Pomegranate Juice
Dietary supplementation with 8 oz. commercially-available pomegranate juice consumed daily.
Dietary Supplement: Pomegranate Juice
Placebo Comparator: Placebo Juice
Dietary supplementation with 8 oz. placebo juice (identical to pomegranate juice but lacking polyphenols) consumed daily.
Dietary Supplement: Placebo Juice



Primary Outcome Measures :
  1. 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).

  2. 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).

  3. 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.


Secondary Outcome Measures :
  1. 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. ]
    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.

  2. 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. ]
    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.


Other Outcome Measures:
  1. Placental weight. [ Time Frame: The placenta will be weighed as part of routine pathology exam within 1-3 days of delivery. ]
    Weight of the placenta measured in grams.

  2. Incidence of pre-eclampsia. [ Time Frame: The electronic medical record will be reviewed within 1 week of delivery. ]
    Incidence of pre-eclampsia requiring medication as documented in the medical record.

  3. Gestational age at delivery. [ Time Frame: The electronic medical record will be reviewed within 1 week of delivery. ]
    Gestational age at delivery based on ultrasound dating acquired at less than 12 weeks' gestation as documented in the medical record.

  4. Incidence of resuscitation at delivery. [ Time Frame: The electronic medical record will be reviewed within 1 week of delivery. ]
    Incidence of infant resuscitation at delivery measured by APGAR scores assigned at birth and documented in the medical record.

  5. Cord gas characteristics. [ Time Frame: The electronic medical record will be reviewed within 1 week of delivery. ]
    Umbilical artery cord gas pH and base deficit as documented in the medical record.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Expecting mother with a fetal diagnosis of less than 5th percentile on the Doubilet fetal growth curve

Exclusion Criteria:

  • Multiple congenital abnormalities
  • Known fetal chromosomal disorder
  • Maternal illicit drug or alcohol intake

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394910


Locations
Layout table for location information
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Brigham and Women's Hospital
University of California, Los Angeles
POM Wonderful LLC
Investigators
Layout table for investigator information
Principal Investigator: Terrie E Inder, MD, MBChB Brigham and Women's Hospital
Layout table for additonal information
Responsible Party: Terrie Inder, Chair, Department of Pediatric Newborn Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04394910    
Other Study ID Numbers: 2014P000870
First Posted: May 20, 2020    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Injuries
Fetal Growth Retardation
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Fetal Diseases
Pregnancy Complications
Growth Disorders
Pathologic Processes