Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics

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.
ClinicalTrials.gov Identifier: NCT03838146
Recruitment Status : Recruiting
First Posted : February 12, 2019
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Linda May, East Carolina University

Brief Summary:
The American Heart Association suggests that heart disease prevention should target pregnancy and the first year of life; however, there is a fundamental gap in knowledge regarding the effects of prenatal exercise on the prevention of heart disease.[1, 2] Insulin resistance in skeletal muscle is believed to be a critical contributor to the metabolic syndrome which increases the risk for cardiovascular disease (CVD). Conversely, exercise improves insulin sensitivity and many other facets of skeletal muscle function and metabolism; however, it is unclear if this positive effect can be "imprinted" in the skeletal muscle of the fetus with maternal exercise and accordingly diminish CVD risk in offspring. Our previous studies found that exercise during pregnancy leads to improved heart measures and reduced adiposity.[3-6] These studies demonstrated the potential for maternal exercise to reduce risk for CVD, but the cellular mechanisms involved, however, are not clearly evident. The proposed project will fill this critical gap and assess the influence of maternal exercise intervention to "imprint" progenitor stem cells in the fetus (umbilical cord tissue) to develop into insulin sensitive skeletal muscle and also improve indices of infant morphometry and movement. Using a randomized design, 160 women will perform either exercise intervention (aerobic training, resistance training, or both) or usual care (controls). Infant cord tissue and blood will be sampled at birth while blood will be sampled at 1 month of age. Similarly, infant neuromotor and morphometric examinations will be performed at 1 month. and at 1-month of age via blood sample, neuromotor, and morphometric examinations. The rationale for the project is to elucidate the effects of maternal exercise on offspring health outcomes and determine specific metabolic targets predictive of offspring long-term disease risk. The investigators will test the central hypothesis that exercise during pregnancy alters skeletal muscle in a manner which decreases the risk of heart disease in offspring. To test this central hypothesis, the investigators will pursue two specific aims: Aim 1- Determine the ability of regular maternal exercise to imprint key myocellular metabolic (insulin sensitivity) properties of offspring mesenchymal stem cells (MSC), neuromotor function, and morphometry. Aim 2- Determine the distinct abilities of regular maternal exercise to imprint the metabolome of offspring MSC.

Condition or disease Intervention/treatment Phase
Exercise Behavioral: Types of Exercise Not Applicable

Detailed Description:
Is offspring skeletal muscle function and metabolism imprinted by regular maternal exercise? What offspring metabolome markers are altered with regular maternal exercise? The investigators will use a randomized design of 160 women to either exercise intervention (aerobic training, resistance training, or both) or usual care (controls). Infant cord tissue and blood will be sampled at birth while blood will be sampled at 1 month of age. Similarly, infant neuromotor and morphometric examinations will be performed at 1 month. and at 1-month of age via blood sample, neuromotor, and morphometric examinations. The rationale for the project is to elucidate the effects of maternal exercise on offspring health outcomes and determine specific metabolic targets predictive of offspring long-term disease risk.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: comparing 3 exercise interventions to a control (non-exercise) group
Masking: Double (Care Provider, Investigator)
Masking Description: the clinicians and investigators taking measures are blinded to group assignment
Primary Purpose: Prevention
Official Title: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : August 30, 2020
Estimated Study Completion Date : August 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Non-Exercise Control
This group will come in regularly for measurements, but will not have an exercise intervention. If necessary for retention of participants, then we will meet with controls 3 times a week to stress reduction techniques.
Experimental: Resistance Type of Exercise
This group will participate in resistance exercise intervention 3 times per week from enrollment to delivery.The resistance training (RT) group will perform three sets of 12-15 repetitions of 10-12 resistance exercises in a circuit, with rest of 30-60 seconds between sets as needed. Participants will use a combination of Cybex machines (Cybex International, Medway, MA), resistance bands, and free weights. Routines will change every 3 weeks to add variety and improve compliance.
Behavioral: Types of Exercise
moderate intensity exercise

Experimental: Combination Type of Exercise
This group will participate in combination (aerobic+resistance) exercise intervention 3 times per week from enrollment to delivery. The combination (CT) group will alternate between resistance and aerobic exercises. Participants will perform 4.5 minute bouts of aerobic exercise and perform four resistance exercises of 12-15 repetition that vary between aerobic bouts[17-19]. The aerobic exercise bouts will be performed on the aerobic machine of the participant's choosing as described above. The resistance routine will follow similar guidelines as the resistance group.
Behavioral: Types of Exercise
moderate intensity exercise

Experimental: Aerobic Type of Exercise
This group will participate in aerobic exercise intervention 3 times per week from enrollment to delivery. The aerobic training (AT) group will perform a continuous aerobic exercise of their choosing (e.g., treadmill, ellipticals, stairs, Zumba, or outside walking/jogging). Participants' ability to choose an aerobic activity that they are comfortable with and enjoy is intended to improve compliance.
Behavioral: Types of Exercise
moderate intensity exercise




Primary Outcome Measures :
  1. Human Skeletal Muscles cells grown from MSCs will have insulin responsiveness measured [ Time Frame: At Birth ]
    Western blot analysis of Akt phosphorylation will be conducted on cell lysates from myotubes under basal or following insulin-stimulation. Glycogen synthesis will be measured under basal and insulin-stimulated conditions. Data will be presented as % change in glycogen synthesis following insulin stimulation.


Secondary Outcome Measures :
  1. Global and targeted metabolomics analysis will be conducted to map out pathways and mechanisms from regular maternal exercise. Docosahexaenoic acid (DHA), Eicosapentaenoic Acid (EPA), Docosapentaenoic Acid (DPA), and Arachidonic acid (ARA). [ Time Frame: At 16 weeks and 36 weeks gestation ]

    Targeted quantitative LC/MS analysis of DHA and EPA from participants at 16 (pre-training intervention) and 36 weeks, DHA and EPA levels from umbilical cord tissue sample, and DHA and EPA levels from umbilical cord (infant) blood will be compared between groups.

    From our pathway analysis of identified metabolites of interest, we will be able to map the metabolites of interest within common pathways related to maternal exercise exposure.


  2. Peabody Developmental Motor Scales, 2nd edition (PDMS-2) will be performed by a pediatric physical therapist (blinded to group classification) to measure gross motor skills of infants up to 12 months of age. [ Time Frame: at 1 month postnatal visit ]

    3 of the 6 subtests can be used on 1 month olds. All items scored from 0-2, which include:

    1. Reflexes: 8-item subtest that measures child's ability to react to environmental events.
    2. Stationary: 30-item subtest that measures child's ability to control body within center of gravity and retain equilibrium
    3. Locomotion: 89-item subtest that measures child's ability to move from one place to another through crawling, walking, running, hopping, and jumping forward

    we only do the Reflexes Range (0-16), Stationary Range (0-60), and Locomotion Range (0-178) subtests. Each subtest score is also converted to percentile (comparing infant's behavior to the normative sample). All subtest score are summed to determine the Gross Motor Quotient (GMQ), and a GMQ percentile score will be determined.


  3. A trained (blinded) researcher will measure bicep, tricep, and subscapular skinfold measures, circumferences (abdominal, head, mid-upper arm), and lengths (body, femur, leg, humeral). All measures are recorded as mm. [ Time Frame: at 1 month postnatal visit ]

    All measures will be taken in duplicate on the right side following published standards for skinfold and circumference location.

    Data will be used to compare individual skinfolds, sum of skinfolds and circumferences measures between groups


  4. A trained (blinded) researcher will measure body weight on an infant scale [ Time Frame: at 1 month postnatal visit ]
    Body weight will be done to the nearest tenth of a kilogram. Data will be used to compare body weight measures between groups



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   our study focuses on exercise exposure during pregnancy, therefore, all participants are female.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • <16 weeks gestation
  • singleton pregnancy telephone/email contact

Exclusion Criteria:

  • chronic conditions i.e. diabetes, hypertension, HIV, etc.
  • use of medications that affect fetal development;
  • use of alcohol, tobacco, or other drugs

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): NCT03838146


Contacts
Layout table for location contacts
Contact: Linda E May, MS, PhD 252-737-7072 mayl@ecu.edu
Contact: Devon Kuehn, MD kuehnd@ecu.edu

Locations
Layout table for location information
United States, North Carolina
East Carolina University Recruiting
Greenville, North Carolina, United States, 27834
Contact: Linda E May, MS, PhD    252-737-7072    mayl@ecu.edu   
Contact: Devon Kuehn, MD       kuehnd@ecu.edu   
Sponsors and Collaborators
East Carolina University
American Heart Association

Layout table for additonal information
Responsible Party: Linda May, Associate Professor, East Carolina University
ClinicalTrials.gov Identifier: NCT03838146     History of Changes
Other Study ID Numbers: 12-002524b
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: we will not be sharing individual data with other researchers

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No