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

Intrauterine Growth Restriction Clinical Trial

— POM-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00788866
• Other study ID #: Pomegranate-1
• Status: Completed
• Phase: N/A
• First received: November 10, 2008
• Last updated: October 16, 2014
• Start date: December 2008
• Est. completion date: October 2014

Study information

• Verified date: October 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Injuries
• Fetal Growth Retardation
• Intrauterine Growth Restriction

Intervention

Dietary Supplement:
• Pomegranate Juice
8 oz of pomegranate juice daily vs placebo juice identical in all respects except pomegranate
• Placebo
Juice that matches the makeup of pomegranate in regards to sugar, vitamin C, etc. The only difference is that it lacks pomegranate juice.

Locations

Country	Name	City	State
United States	St Louis Children's Hospital	St Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	POM Wonderful LLC, University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal compliance	Daily dietary report; Increase in polyphenol levels	To delivery	No
Other	Analysis both by 'intention to treat' and 'as treated'		To discharge	No
Primary	CNS injury at term by MR Imaging	Qualitative MRI injury- white matter injury (WMI) and gray matter injury (GMI); Brain Metrics on MR imaging; Diffusion- apparent diffusion coefficient (ADC) and fractional anisotropy (FA); Spectroscopy- lactate and NAA levels in the basal ganglia; Advanced MRI development indices - brain volumes, surface based morphology (SBM, folding indices)	36 - 41 weeks (post delivery)	No
Secondary	Placental morphology: weight and size		At birth	No
Secondary	Gestational age at delivery		At birth	No
Secondary	Birth weight		At birth	No
Secondary	Ellagic acid levels from cord blood		To discharge	No
Secondary	Dubowitz neurologic exam at term		To discharge	No
Secondary	Time to full oral feeds		To discharge	No
Secondary	ROP		To discharge	No
Secondary	NEC		To discharge	No
Secondary	Length of ventilatory support		To discharge	No
Secondary	Time to discharge		To discharge	No
Secondary	Placental micrography: number of villi, vasculature, collagen content		At birth	No
Secondary	Placental immunohistochemistry: proliferation, apoptosis and differentiation		At birth	No
Secondary	Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases		At birth	No
Secondary	Placental RNA microarray		At birth	No
Secondary	Umbilical cord gases		At birth	No
Secondary	Pregnancy complications: preeclampsia		At birth	No
Secondary	Neonatal wellbeing: APGAR scores, need for resuscitation		At birth	No