Intrauterine Growth RestrictionPOM-1NCT00788866
Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
A study testing Pomegranate Juice in people with Intrauterine Growth Restriction, run by Washington University School of Medicine at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age, 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
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Oct 2014
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Healthy expecting mothers two weeks from their expected due dates
- No evidence of IUGR
- No evidence of fetal problems
- Phase II:
- Expecting mother with a fetal diagnosis of intrauterine growth restriction (IUGR) defined by estimated fetal weight <10th percentile for gestational age
- 24 - 34 weeks gestation
Who cannot join
- Major congenital abnormalities
- Known fetal chromosomal disorder
- Maternal illicit drug use
- Maternal IV and Hepatitis C infection
- Premature rupture of membranes
Trial locations and contacts
1 site in 1 country.
United States1 site
St Louis Children's Hospital
St Louis, Missouri, 63110
About this study
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.
Read the 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.
- Conditions
- Intrauterine Growth Restriction
- Being tested
- Pomegranate Juice, Placebo
- Keywords
- Neuroprotection, Antioxidants, Neonatal brain injury, Pomegranate 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
8 oz of pomegranate juice daily vs placebo juice identical in all respects except pomegranate
PlaceboDietary supplement
Juice that matches the makeup of pomegranate in regards to sugar, vitamin C, etc. The only difference is that it lacks pomegranate juice.
| Study group | Role | What they receive |
|---|---|---|
| Pomegranate juice | Experimental | This arm with receive 8oz of pomegranate juice per day. Receives: Dietary Supplement: Pomegranate Juice |
| Placebo | Placebo comparator | This group will take 8oz of placebo juice that lacks pomegranate daily Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 36 - 41 weeks (post delivery)
Secondary outcomes (17)
Placental morphology: weight and size
Measured: At birth
Gestational age at delivery
Measured: At birth
Birth weight
Measured: At birth
Ellagic acid levels from cord blood
Measured: To discharge
Dubowitz neurologic exam at term
Measured: To discharge
Time to full oral feeds
Measured: To discharge
ROP
Measured: To discharge
NEC
Measured: To discharge
Length of ventilatory support
Measured: To discharge
Time to discharge
Measured: To discharge
Placental micrography: number of villi, vasculature, collagen content
Measured: At birth
Placental immunohistochemistry: proliferation, apoptosis and differentiation
Measured: At birth
Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases
Measured: At birth
Placental RNA microarray
Measured: At birth
Umbilical cord gases
Measured: At birth
Pregnancy complications: preeclampsia
Measured: At birth
Neonatal wellbeing: APGAR scores, need for resuscitation
Measured: At birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2008 (estimated)
- Study startDec 2008
- Primary completionOct 2014
- Study completionOct 2014
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 Washington University School of MedicineThe 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
- Single group
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- POM Wonderful LLC, University of California, Los Angeles
- Responsible party
- Principal investigator, Methodius Tuuli, MD, MPH, Washington University Early Recognition Center
- Investigators
- Michael Nelson, MD, MPH, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00788866
- Sponsor's protocol ID
- Pomegranate-1
- Acronym
- POM-1
- Status last verified
- Oct 2014
- First submitted
- 10 Nov 2008
- Last updated
- 17 Oct 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Matthews LG, Smyser CD, Cherkerzian S, Alexopoulos D, Kenley J, Tuuli MG, Nelson DM, Inder TE. Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: A randomized controlled pilot study. PLoS One. 2019 Aug 21;14(8):e0219596. doi: 10.1371/journal.pone.0219596. eCollection 2019.
PubMed 31433809
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Maternal Pomegranate Juice on Brain Injury in Infants With Intrauterine Growth Restriction (IUGR)
- ClinicalTrials.gov ID
- NCT00788866
- Acronym / sponsor ID
- POM-1 / Pomegranate-1
- Conditions
- Intrauterine Growth Restriction
- Keywords
- Neuroprotection, Antioxidants, Neonatal brain injury, Pomegranate juice
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- POM Wonderful LLC, University of California, Los Angeles
- Study start
- Dec 2008
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 11 Nov 2008 (estimated)
- 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 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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pomegranate juice | Experimental | Dietary Supplement: Pomegranate JuiceThis arm with receive 8oz of pomegranate juice per day. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboThis group will take 8oz of placebo juice that lacks pomegranate daily |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy expecting mothers two weeks from their expected due dates
- No evidence of IUGR
- No evidence of fetal problems
- Expecting mother with a fetal diagnosis of intrauterine growth restriction (IUGR) defined by estimated fetal weight <10th percentile for gestational age
- 24 - 34 weeks gestation
Key exclusion criteria (5 listed)
- Major congenital abnormalities
- Known fetal chromosomal disorder
- Maternal illicit drug use
- Maternal IV and Hepatitis C infection
- Premature rupture of membranes
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 Juice8 oz of pomegranate juice daily vs placebo juice identical in all respects except pomegranate | Dietary supplement | Pomegranate juice |
| PlaceboJuice that matches the makeup of pomegranate in regards to sugar, vitamin C, etc. The only difference is that it lacks pomegranate juice. | Dietary supplement | Placebo |
Primary outcome
CNS injury at term by MR Imaging
Time frame: 36 - 41 weeks (post delivery)
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)
17 secondary outcomes
Placental morphology: weight and size
Time frame: At birth
Gestational age at delivery
Time frame: At birth
Birth weight
Time frame: At birth
Ellagic acid levels from cord blood
Time frame: To discharge
Dubowitz neurologic exam at term
Time frame: To discharge
Time to full oral feeds
Time frame: To discharge
ROP
Time frame: To discharge
NEC
Time frame: To discharge
Length of ventilatory support
Time frame: To discharge
Time to discharge
Time frame: To discharge
Placental micrography: number of villi, vasculature, collagen content
Time frame: At birth
Placental immunohistochemistry: proliferation, apoptosis and differentiation
Time frame: At birth
Placental: immunoassays: HSP90, lipid hydroperoxide, nitrotyrosine assay, paraoxonase 1 expression, superoxide dismutases
Time frame: At birth
Placental RNA microarray
Time frame: At birth
Umbilical cord gases
Time frame: At birth
Pregnancy complications: preeclampsia
Time frame: At birth
Neonatal wellbeing: APGAR scores, need for resuscitation
Time frame: At birth
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 17 Oct 2014.
- Derived from this study: PubMed 31433809Matthews LG, Smyser CD, Cherkerzian S, Alexopoulos D, Kenley J, Tuuli MG, Nelson DM, Inder TE. Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: A randomized controlled pilot study. PLoS One. 2019 Aug 21;14(8):e0219596. doi: 10.1371/journal.pone.0219596. eCollection 2019.
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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.
Michael Nelson, MD, MPH principal investigator
Washington University School of Medicine
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 Washington University School of Medicine 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 6 inclusion and 5 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 17 Oct 2014. 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?
CNS injury at term by MR Imaging (time frame: 36 - 41 weeks (post delivery)). 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 NCT00788866, 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 17 Oct 2014.