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Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols

Primary Purpose

Pregnancy Complications

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
restrict polyphenol-rich foods
Sponsored by
Instituto de Cardiologia do Rio Grande do Sul
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pregnancy Complications focused on measuring polyphenols, pregnant, fetal ductal constriction, prostaglandin E2

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria

  • Pregnancy with diagnosis of fetal ductal constriction
  • Single fetus
  • gestational age from 28 weeks

Exclusion Criteria

  • cardiac malformations
  • restricted intrauterine growth
  • increased nuchal translucency
  • present or suspected chromosomal disorders
  • signs of any type of hydrops fetalis
  • pregnancy
  • hypertension
  • diabetes mellitus
  • structural or functional cardiac disorders
  • current use of nonsteroidal anti-inflammatory drugs, steroids, antidepressants, illicit drugs, alcohol or smoking
  • multiple pregnancy
  • having received previous nutritional guidance in relation to restricted intake of polyphenol-rich foods

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    No Intervention

    Arm Label

    interventional group

    control group

    Arm Description

    The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods

    healthy group as comparator

    Outcomes

    Primary Outcome Measures

    Plasma levels of prostaglandin E2 (PGE2)
    PGE2 was quantified by capture ELISA. The measurements were obtained through 4-parameter linear regression (Excel, Microsoft), and data were expressed in picograms of protein per milliliter (pg/mL).

    Secondary Outcome Measures

    Consumption of foods rich in Total Polyphenols (TP)
    TP on the maternal diet were quantified using a Food Frequency Questionnaire (FFQ) validated for pregnant women. TP results after analysis of the dietary questionnaires were described in milligrams (mg)

    Full Information

    First Posted
    March 29, 2017
    Last Updated
    April 7, 2017
    Sponsor
    Instituto de Cardiologia do Rio Grande do Sul
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03111602
    Brief Title
    Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
    Official Title
    Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    May 2011 (Actual)
    Primary Completion Date
    June 2015 (Actual)
    Study Completion Date
    February 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Instituto de Cardiologia do Rio Grande do Sul

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    INCREASE OF PROSTAGLANDIN E2 IN REVERSAL OF DUCTAL CONSTRICTION AFTER DIETARY RESTRICTION OF POLYPHENOLS. Clinical trial with a healthy group as comparator. The interventional group was made up of third-trimester mothers whose single fetuses had ductal constriction, excluding those exposed to NSAID, and the control group only by third-trimester normal fetuses. The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods and both groups answered a food frequency questionnaire after fetal Doppler-echocardiographic examination and blood draw for PGE2 levels analysis. After two weeks, the women were again submitted to fetal echocardiogram, dietary assessment and blood draw.
    Detailed Description
    INCREASE OF PROSTAGLANDIN E2 IN REVERSAL OF DUCTAL CONSTRICTION AFTER DIETARY RESTRICTION OF POLYPHENOLS. Fetal ductal constriction is a clinical situation with high morbidity and potential mortality. Patency the fetal ductus arteriosus (DA) depends on circulating prostaglandin (PG), which is produced by the cyclooxygenase (COX) pathway during inflammatory response(1) and from the third trimester of pregnancy on, is physiologically released. COX-inhibiting substances, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can interfere with PG metabolism and induce constriction of the DA. To treat or prevent DA constriction, it is therefore important to reduce fetal exposure to drugs that may interfere with prostaglandin biosynthesis, such as natural anti-inflammatory drugs and polyphenol-rich foods. Polyphenols, the most abundant antioxidants present in the diet, are widely distributed in vegetable foods. One of the possible mechanisms to explain their activity is inhibition of synthesis and release of inflammatory mediators. However, clinical studies investigating the effect of polyphenols on inflammatory responses are inconclusive and, in most cases, only evaluate clinical outcomes. The role of polyphenols on the inflammatory response, and associated modifications of the plasma concentration of PGE2 in pregnant women, has not yet been studied. Despite the potential benefits of a diet rich in polyphenols, a high consumption of these substances in the third trimester of pregnancy may reduce plasma levels of PGE2 and result in DA constriction,so that a restriction in their ingestion during this period is already recommended.This functional problem has high prevalence and may result in severe fetal and neonatal complications. These considerations raised the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods is accompanied by increased in prostaglandin E2 levels. Demonstration of this effect would represent an advancement in knowledge and might result in changes in dietary guidance during pregnancy and prevention of perinatal complications, with potential impact in terms of public health. The aim of this study was to test the hypothesis that reversal of fetal ductal constriction in the third trimester of pregnancy, after maternal restriction of polyphenol-rich foods, is accompanied by increased plasma levels of prostaglandin E2.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pregnancy Complications
    Keywords
    polyphenols, pregnant, fetal ductal constriction, prostaglandin E2

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Clinical trial with a healthy group as comparator.
    Masking
    Care ProviderInvestigator
    Masking Description
    Researchers were blinded to the allocation data of pregnant women in the groups
    Allocation
    Non-Randomized
    Enrollment
    75 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    interventional group
    Arm Type
    Experimental
    Arm Description
    The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods
    Arm Title
    control group
    Arm Type
    No Intervention
    Arm Description
    healthy group as comparator
    Intervention Type
    Other
    Intervention Name(s)
    restrict polyphenol-rich foods
    Intervention Description
    dietary orientation to restrict polyphenol-rich foods
    Primary Outcome Measure Information:
    Title
    Plasma levels of prostaglandin E2 (PGE2)
    Description
    PGE2 was quantified by capture ELISA. The measurements were obtained through 4-parameter linear regression (Excel, Microsoft), and data were expressed in picograms of protein per milliliter (pg/mL).
    Time Frame
    baseline and two weeks
    Secondary Outcome Measure Information:
    Title
    Consumption of foods rich in Total Polyphenols (TP)
    Description
    TP on the maternal diet were quantified using a Food Frequency Questionnaire (FFQ) validated for pregnant women. TP results after analysis of the dietary questionnaires were described in milligrams (mg)
    Time Frame
    baseline and two weeks
    Other Pre-specified Outcome Measures:
    Title
    Diagnostic parameters of fetal ductus arteriosus constriction
    Description
    The peak systolic, peak diastolic and end diastolic velocities (m/s) were determined. The pulsatility index of the ductus arteriosus was calculated automatically by the echocardiography system after manual tracing of the spectral curve, using the formula: (peak systolic velocity - diastolic peak velocity)/mean velocity.
    Time Frame
    baseline and two weeks

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Gender Eligibility Description
    pregnant: third-trimester mothers
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria Pregnancy with diagnosis of fetal ductal constriction Single fetus gestational age from 28 weeks Exclusion Criteria cardiac malformations restricted intrauterine growth increased nuchal translucency present or suspected chromosomal disorders signs of any type of hydrops fetalis pregnancy hypertension diabetes mellitus structural or functional cardiac disorders current use of nonsteroidal anti-inflammatory drugs, steroids, antidepressants, illicit drugs, alcohol or smoking multiple pregnancy having received previous nutritional guidance in relation to restricted intake of polyphenol-rich foods

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    23316751
    Citation
    Vian I, Zielinsky P, Zilio AM, Mello A, Lazzeri B, Oliveira A, Lampert KV, Piccoli A, Nicoloso LH, Bubols GB, Garcia SC. Development and validation of a food frequency questionnaire for consumption of polyphenol-rich foods in pregnant women. Matern Child Nutr. 2015 Oct;11(4):511-24. doi: 10.1111/mcn.12025. Epub 2013 Jan 15.
    Results Reference
    background
    PubMed Identifier
    16257930
    Citation
    Momma K, Toyoshima K, Takeuchi D, Imamura S, Nakanishi T. In vivo constriction of the fetal and neonatal ductus arteriosus by a prostanoid EP4-receptor antagonist in rats. Pediatr Res. 2005 Nov;58(5):971-5. doi: 10.1203/01.pdr.0000182182.49476.24.
    Results Reference
    background
    PubMed Identifier
    22052330
    Citation
    Zielinsky P, Piccoli AL Jr, Manica JL, Nicoloso LH, Vian I, Bender L, Pizzato P, Pizzato M, Swarowsky F, Barbisan C, Mello A, Garcia SC. Reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods: an open clinical trial. J Perinatol. 2012 Aug;32(8):574-9. doi: 10.1038/jp.2011.153. Epub 2011 Nov 3.
    Results Reference
    background

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    Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols

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