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Investigation of Mechanisms for Transmission of Impaired Glucose Metabolism in Infants Exposed to Diabetes in Utero (IMAGINE)

This study is currently recruiting participants.
Verified November 2017 by Leanne Redman, Pennington Biomedical Research Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02926079
First Posted: October 6, 2016
Last Update Posted: November 21, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
University of Colorado, Denver
Information provided by (Responsible Party):
Leanne Redman, Pennington Biomedical Research Center
  Purpose
This proposed study; Investigation of mechanisms for transmission of impaired glucose metabolism in infants exposed to diabetes in utero, will test the overarching hypothesis that impaired maternal substrate oxidation (metabolic inflexibility) and placental lipotoxicity are characteristics of diabetic pregnancies and in utero development within these conditions programs a metabolically inflexible phenotype in the offspring.

Condition
Pregnancy Gestational Diabetes Mellitus

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Investigation of Mechanisms for Transmission of Impaired Glucose Metabolism in Infants Exposed to Diabetes in Utero

Further study details as provided by Leanne Redman, Pennington Biomedical Research Center:

Primary Outcome Measures:
  • Metabolic flexibility - Mother [ Time Frame: 33-35 weeks of gestation ]
    Assessed before and after meal test by measuring RMR via indirect calorimetry


Secondary Outcome Measures:
  • Metabolic Flexibility - Infant [ Time Frame: 10-30 days of life ]
    Assessed before and after a meal test of infant formula and measurement of RMR in an infant metabolic chamber

  • Higher fat content in placenta of mothers with GDM [ Time Frame: Birth ]
    Placental samples will be assessed for lipid content via immunohistochemistry antibody staining for lipid droplet proteins and by Oil Red O staining.

  • Lower mitochondrial oxygen consumption rates in placenta of mothers with GDM [ Time Frame: Birth ]
    Isolated mitochondria from placental tissue will be assessed for oxygen consumption rates using the Sea Horse device.

  • Higher fat content in umbilical cord mesenchymal stem cells from mothers with GDM [ Time Frame: Birth ]
    Mesenchymal stem cells will be differentiated to a myogenic state and assessed for lipid content via Oil Red O staining

  • Lower oxygen consumption rates in umbilical cord mesenchymal stem cells from mothers with GDM [ Time Frame: Birth ]
    Mesenchymal stem cells will be differentiated to a myogenic state and assessed for oxygen consumption rates using the Oroboros device.


Biospecimen Retention:   Samples Without DNA

Maternal Blood Collection: Approximately 33mL of blood will be collected during the visit.

Infant Blood Collection: Approximately 2mL of blood will be collected during the visit.


Estimated Enrollment: 20
Study Start Date: December 2016
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pregnant women diagnosed with gestational diabetes
Pregnant women with normal pregnancy

Detailed Description:

This translational research study will obtain paired measures of metabolic flexibility (postprandial RQ minus basal RQ) in response to a standardized meal by indirect calorimetry in mother:infant dyads of diabetic and non-diabetic pregnancies. The downstream effects of the intrauterine exposure to diabetes and gestational lipotoxicity will be tested in the infant: 1) at birth by studying adipogenic pathways and mitochondrial function in umbilical cord mesenchymal stem cells cultured in myogenic conditions[13], and 2) by studying metabolic flexibility in the infant in a whole body infant calorimeter in response to a standardized meal.

Mothers will be enrolled between (33-35 weeks of gestation) and their infants will be enrolled between 10-30 days of life with the following aims.

Aim 1. Characterize metabolic flexibility and lipotoxicity in diabetic and non-diabetic pregnancies.

Hypothesis 1A: In response to a standardized meal in late pregnancy, diabetic pregnancies will be metabolically inflexible (blunted switch in RQ from the fasted state to the postprandial state) compared to non-diabetic pregnancies matched for maternal age and pregravid BMI.

Hypothesis 1B: Placenta from diabetic pregnancies will have higher lipid content, reduced mitochondrial content and lower rates of mitochondrial oxygen consumption compared to placenta from non-diabetic pregnancies.

Aim 2. Test whether intrauterine exposure to maternal diabetes infers disordered substrate oxidation in offspring at birth (in myocytes cultured from umbilical cord mesenchymal stem cells) and early in postnatal life (metabolic flexibility in response to a standardized meal).

Hypothesis 2A: Umbilical cord mesenchymal stem cells cultured in myogenic conditions from diabetic pregnancies will have greater lipid content, reduced mitochondrial content, and lower rates of mitochondrial electron transport oxygen consumption and fatty acid oxidation.

Hypothesis 2B: In response to a standardized meal, offspring of diabetic pregnancies will be metabolically inflexible (blunted switch in RQ from the pre- to postprandial state) compared to offspring of non-diabetic pregnancies.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Up to 20 pregnant women with and without gestational diabetes mellitus with a BMI between 20 kg/m2 and 40 kg/m2 prior to the current pregnancy.
Criteria

Inclusion Criteria (Mother):

  • BMI between 20 kg/m2 and 40 kg/m2 prior to the current pregnancy (determined by self-report and confirmation of pregravid BMI of the index pregnancy from the prenatal record)
  • Completion of standardized glucose tolerance testing (between 24-28 weeks gestation) in the index pregnancy; either a single 2 hour, 75g glucose tolerance test or the two-step: 1 hour 50g and 3 hour 100g glucose tolerance test to confirm diagnosis of gestational diabetes mellitus or normal glucose tolerance
  • Prior history of Cesarean section or planned Cesarean section for current pregnancy
  • Medically cleared for participation in the study by primary care obstetrician or midwife
  • Medically cleared for participation by the Medical Investigator
  • Medical record release (prenatal record, hospital delivery record) for study staff to access information in the medical record related to the current and if applicable, the prior pregnancy.
  • Willingness to enroll the infant in the study provided inclusion/exclusion criteria pertaining to the infant are met

Inclusion criteria (Infant):

  • Born full-term (>37,0 weeks gestation)
  • Available for clinical assessments between 10-30 days old
  • Healthy

Exclusion Criteria (Mother):

  • Use of insulin therapy in the index pregnancy
  • History of preterm birth
  • History of intrauterine growth-restriction
  • Evidence of gestational hypertension (SBP >160 mmHg & DBP >110 mmHg)
  • HIV or AIDS (self-reported)
  • Planned termination of pregnancy or adoption or unwillingness to enroll the infant in the study

Exclusion Criteria (Infant):

  • Using medications to treat a chronic condition (does not include use of vitamin supplements or PRN medication for flatulence)
  • Unwilling or unable to be fed 2 fl oz of infant formula
  • Diagnosed with a congenital abnormality or disability that would render testing unsafe or would interfere with data collection
  Contacts and Locations
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): NCT02926079


Contacts
Contact: Nicholas T Broskey, PhD 225-763-3141 nick.broskey@pbrc.edu

Locations
United States, Louisiana
Pennington Biomedical Research Center Recruiting
Baton Rouge, Louisiana, United States, 70808
Contact: Nicholas Broskey, PhD    225-763-3141    nick.broskey@pbrc.edu   
Sponsors and Collaborators
Pennington Biomedical Research Center
University of Colorado, Denver
Investigators
Principal Investigator: Leanne M Redman, PhD Pennington Biomedical Research Center
  More Information

Responsible Party: Leanne Redman, Associate Professor, Pennington Biomedical Research Center
ClinicalTrials.gov Identifier: NCT02926079     History of Changes
Other Study ID Numbers: PBRC 2016-071
First Submitted: September 19, 2016
First Posted: October 6, 2016
Last Update Posted: November 21, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes, Gestational
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pregnancy Complications