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Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR) (POM-1)

This study has been completed.
Sponsor:
Collaborators:
POM Wonderful LLC
University of California, Los Angeles
Information provided by (Responsible Party):
Methodius Tuuli, MD, MPH, Washington University Early Recognition Center
ClinicalTrials.gov Identifier:
NCT00788866
First received: November 10, 2008
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

Infants with intrauterine growth restriction are known to be at increased risk for long term neurodevelopmental delay into adulthood. The main mechanism for this is likely decreased blood flow to the brain secondary to altered placental blood flow. Antioxidants may serve to protect the developing brain from this process. Animal studies have shown that pomegranate juice protects the fetal brain from injury in a model of stroke. This clinical trial is intended to evaluate if giving mothers pomegranate juice during the last several weeks of pregnancy can help protect intrauterine growth restricted babies' brains.


Condition Intervention
Intrauterine Growth Restriction
Dietary Supplement: Pomegranate Juice
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • CNS injury at term by MR Imaging [ Time Frame: 36 - 41 weeks (post delivery) ] [ Designated as safety issue: No ]
    1. Qualitative MRI injury- white matter injury (WMI) and gray matter injury (GMI)
    2. Brain Metrics on MR imaging
    3. Diffusion- apparent diffusion coefficient (ADC) and fractional anisotropy (FA)
    4. Spectroscopy- lactate and NAA levels in the basal ganglia
    5. Advanced MRI development indices - brain volumes, surface based morphology (SBM, folding indices)


Secondary Outcome Measures:
  • Placental morphology: weight and size [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Gestational age at delivery [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Birth weight [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Ellagic acid levels from cord blood [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • Dubowitz neurologic exam at term [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • Time to full oral feeds [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • ROP [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • NEC [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • Length of ventilatory support [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • Time to discharge [ Time Frame: To discharge ] [ Designated as safety issue: No ]
  • Placental micrography: number of villi, vasculature, collagen content [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Placental immunohistochemistry: proliferation, apoptosis and differentiation [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Placental RNA microarray [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Umbilical cord gases [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Pregnancy complications: preeclampsia [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Neonatal wellbeing: APGAR scores, need for resuscitation [ Time Frame: At birth ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Maternal compliance [ Time Frame: To delivery ] [ Designated as safety issue: No ]
    1. Daily dietary report
    2. Increase in polyphenol levels

  • Analysis both by 'intention to treat' and 'as treated' [ Time Frame: To discharge ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: December 2008
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pomegranate juice
This arm with receive 8oz of pomegranate juice per day.
Dietary Supplement: Pomegranate Juice
8 oz of pomegranate juice daily vs placebo juice identical in all respects except pomegranate
Placebo Comparator: Placebo
This group will take 8oz of placebo juice that lacks pomegranate daily
Dietary Supplement: Placebo
Juice that matches the makeup of pomegranate in regards to sugar, vitamin C, etc. The only difference is that it lacks pomegranate juice.

Detailed Description:

This study is divided into two separate phases.

Phase I evaluated if the antioxidants produced from pomegranate juice cross the placenta in normal healthy pregnancies. Twenty women were enrolled, 10 who will take 8 oz of pomegranate juice daily and then 10 others who will take 8 oz of placebo juice without pomegranate daily. Blood samples were first collected from the woman at the time enrollment and then from both the woman and the cord blood at the time of delivery. These blood samples were analyzed to measure the levels of antioxidant metabolites from the pomegranate juice. This phase was deigned to confirm placental transfer of antioxidant pomegranate metabolites. The results confirmed placenta transfer of pomegranate metabolites. Further, placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts.

Phase II focuses on pregnancies with intrauterine growth restriction. If they meet entry criteria, then woman will be enrolled and randomized into 1 of 2 groups.

Treatment group: Expecting mothers in this group will start a daily regimen of 8 oz glass of pomegranate juice. They will keep a daily diary documenting their compliance. They will continue this daily intake up until delivery of their infant.

Placebo group: These women will start a daily regimen of an 8 oz of pomegranate free juice placebo that matches taste, calories, and appearance to regular pomegranate juice but lacks polyphenols. They will also keep a diary of daily intake to help ensure compliance similar to the treatment group. They too will continue to take the placebos up until the time they deliver.

Both groups: All women will be followed up on a weekly basis to assess compliance. A detailed diet history will be collected from the women at the time of enrollment, midway through the 3rd trimester and at the time of delivery. Furthermore, all women will have a detailed social history collected at the time of enrollment. Upon delivery, cord blood will be collected and sent for ellagic acid, a polyphenic component. All placental material will be sent for formal pathological exam and analyzed for markers of placental injury.

If clinically stable, the infants will receive MRI evaluations to evaluate for possible brain injury.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Phase I:

Inclusion Criteria:

  • Healthy expecting mothers two weeks from their expected due dates
  • No evidence of IUGR
  • No evidence of fetal problems

Phase II:

Inclusion Criteria:

  1. Expecting mother with a fetal diagnosis of intrauterine growth restriction (IUGR) defined by estimated fetal weight <10th percentile for gestational age
  2. 24 - 34 weeks gestation

Exclusion Criteria:

  1. Major congenital abnormalities
  2. Known fetal chromosomal disorder
  3. Maternal illicit drug use
  4. Maternal IV and Hepatitis C infection
  5. Premature rupture of membranes
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00788866

Locations
United States, Missouri
St Louis Children's Hospital
St Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
POM Wonderful LLC
University of California, Los Angeles
Investigators
Principal Investigator: Michael Nelson, MD, MPH Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Methodius Tuuli, MD, MPH, Assistant Professor, Washington University Early Recognition Center
ClinicalTrials.gov Identifier: NCT00788866     History of Changes
Other Study ID Numbers: Pomegranate-1
Study First Received: November 10, 2008
Last Updated: October 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Neuroprotection
Antioxidants
Neonatal brain injury
Pomegranate juice

Additional relevant MeSH terms:
Brain Injuries
Fetal Growth Retardation
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Fetal Diseases
Growth Disorders
Nervous System Diseases
Pathologic Processes
Pregnancy Complications
Trauma, Nervous System
Wounds and Injuries

ClinicalTrials.gov processed this record on November 27, 2014