Acute Exercise Effects in Obese Pregnancy

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03750695
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 3
• Actual Duration (Months): 16.3
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Obesity before and during pregnancy is associated with a higher risk for a number of obstetric and metabolic complications in women and their offspring. Of particular importance, obese women have a higher risk of developing gestational diabetes and preeclampsia. In addition, obese women have larger offspring who have a higher risk for the development of obesity and diabetes; both largely attributed to higher maternal glycemia and glucose intolerance during pregnancy. Thus, identifying rehabilitative interventions that improve maternal and offspring metabolic and cardiovascular health in obese pregnancy are critical and have immediate and generational impact. Resistance and aerobic exercise training is a clinical staple for improving musculoskeletal, metabolic and cardiovascular health in non-gravid adolescents and adults with obesity however little is known regarding the effects of exercise during obese pregnancy. This study proposes to collect preliminary data on the independent effects of acute aerobic and resistance rehabilitative exercise on glucose metabolism and vascular function during pregnancy in n=15 obese women in order to inform a large, multisite clinical trial examining the acute and chronic effects of aerobic and resistance exercise on glucose metabolism and vascular function in normal weight, overweight and obese women during pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Complications; Obesity; Pre-Eclampsia; Gestational Diabetes	Behavioral: Resistance exercise; Behavioral: Aerobic Exercise; Behavioral: Rest	N/A

Detailed Description

Maternal obesity prevalence is at a historic high with over 1 in 3 women entering pregnancy obese and 1 in 10 extremely obese. Obesity before and during pregnancy is associated with a higher risk for a number of obstetric and metabolic complications in women and their offspring. Of particular importance, obese women have a higher risk of developing gestational diabetes and preeclampsia. In addition, obese women have larger offspring who have a higher risk for the development of obesity and diabetes; both largely attributed to higher maternal glycemia and glucose intolerance during pregnancy. Thus, identifying rehabilitative interventions that improve maternal and offspring metabolic and cardiovascular health in obese pregnancy are critical and have immediate and generational impact.

Resistance and aerobic exercise training is a clinical staple for improving musculoskeletal, metabolic and cardiovascular health in non-gravid adolescents and adults with obesity. Observational studies suggest that exercise in pregnancy is safe and higher levels of physical activity before and during pregnancy in normal weight (i.e. lean) women reduces the risk of gestational diabetes and gestational hypertensive disorders; however, little is known regarding the effects of exercise training during obese pregnancy and several important questions still exist. These include: 1) "What are the acute and chronic effects of maternal exercise on glucose metabolism and vascular function?", 2) "Are there different effects of aerobic and resistance type exercise on glucose metabolism and vascular function?" and 3) "What are the physiologic and molecular transducers of maternal aerobic and resistance exercise for changes in maternal glucose metabolism and vascular function during pregnancy?" This pilot project aims to collect preliminary data on these questions.

This proposal would be the first study to collect preliminary data on the independent effects of acute aerobic and resistance rehabilitative exercise in pregnancy, and further, in obese women; a population with a high morbidity during gestation. In addition, this proposal would inform a large, multisite clinical trial examining the acute and chronic effects of aerobic and resistance exercise on glucose metabolism and vascular function in normal weight, overweight and obese women during pregnancy. Moreover, this proposal would provide initial evidence of molecular transducers of acute physical activity/rehabilitative exercise necessary for a large, comprehensive clinical trial examining the molecular transducers of rehabilitative exercise in normal weight, overweight and obese women during different stages of pregnancy.

Specific Aim #1: To characterize the acute effects of aerobic and resistance exercise on glucose metabolism (tolerance, insulin sensitivity and β-cell function) in obese women during mid-pregnancy.

Specific Aim #2: To characterize the acute effects of aerobic and resistance exercise on vascular function in obese women during mid-pregnancy.

Specific Aim #3: To explore the molecular transducers of physiologic responses in glucose metabolism and vascular function following acute aerobic and resistance exercise in obese women during mid-pregnancy.

The hypothesis is that acute aerobic and resistance rehabilitative exercise will improve post-exercise glucose metabolism and vascular function in obese women during mid-pregnancy. In a subsequent multi-site clinical trial, this study will examine differences in physiologic effects and molecular transducers of aerobic and resistance exercise on glucose metabolism and vascular function during different stages of pregnancy in overweight and obese women.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Single group crossover design of acute effects of resistance exercise, aerobic exercise or rest (control) on maternal vascular function and glucose metabolismSingle group crossover design of acute effects of resistance exercise, aerobic exercise or rest (control) on maternal vascular function and glucose metabolism
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Acute Effects of Aerobic and Resistance Exercise on Maternal Glucose Metabolism and Vascular Function in Obese Pregnancy
• Actual Study Start Date: Nov 20, 2018
• Actual Primary Completion Date: Mar 31, 2020
• Actual Study Completion Date: Mar 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acute Resistance Exercise One acute exercise session of 40 minutes of resistance exercise	Behavioral: Resistance exercise; One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise
Experimental: Acute Aerobic Exercise One acute session of 40 minutes of aerobic exercise	Behavioral: Aerobic Exercise; One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak)
Placebo Comparator: Acute Resting Session One session of 40 minutes of quiet rest	Behavioral: Rest; 40 minutes of quiet rest in semi-recumbent position

Outcome Measures

Primary Outcome Measures

1. Oral Glucose Insulin Sensitivity (OGIS) Index [2 hours post-intervention, up to approximately 3 hours]

   Oral Glucose Insulin Sensitivity (OGIS) during a 2-hour oral glucose tolerance test. OGIS (an acronym for Oral Glucose Insulin Sensitivity) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. Mari, et al. OGIS uses modeling of glucose values at 0, 90, 120 min and insulin values at 0 and 90 min (2-h OGTT) to calculate the index. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 2001 Mar;24(3):539-48. The formula for OGIS is the following: (glucose clearance rate + square root(glucose clearance rate*glucose clearance rate + 4*pp5*pp6(glucose at 90 min-gcl)*330))/2. A calculation spreadsheet for OGIS is found at: http://webmet.pd.cnr.it/ogis/index.php

2. Percent Change in Endothelial Function [baseline and immediately post-intervention, approximately 40 minutes]

   Augmentation index: reactive hyperemic response post-blood pressure cuff inflation. Reactive hyperemia is the transient increase in organ blood flow that occurs following a brief period of ischemia (e.g., arterial occlusion).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. First trimester BMI ≥ 30.0 and <45.0 kg/m2 (calculated from clinical weight and height)

2. Singleton gestation, between 23 weeks and 0/7 days and 28 weeks and 0/7 days

3. Normal fetal anatomy (no major structural abnormalities identified on standard of care survey before enrollment)

4. Established prenatal care at Women's Health Clinic before 18 weeks of gestation, plans to deliver at Barnes-Jewish Hospital

5. Permission from Obstetrics physician provider to participate in study.

Exclusion Criteria:

1. Gestational or pre-gestational diabetes diagnosis

2. Inability to provide voluntary consent

3. Currently using illegal drugs (e.g., cocaine, methamphetamine, opiates) (safety risk and potential confounding)

4. Current smoker who does not agree to stop (confounding)

5. Participation in routine (>1x/week) exercise program (may improve glucose metabolism/vascular function)

6. History of heart disease, orthopedic, metabolic or neurological condition that would contraindicate exercise (safety risk)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: William Cade, PhD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 23, 2018

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03750695
• Other Study ID Numbers: Pro00105627
• First Posted: Nov 23, 2018
• Last Update Posted: Jul 16, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Duke University: exercise; glucose; vascular
• Additional relevant MeSH terms: Diabetes, Gestational; Eclampsia; Pre-Eclampsia; Pregnancy Complications

Study Results

Participant Flow

Pre-assignment Detail	The 3 interventions were: 1) 1-hour of rest, 2) 1-hour of resistance exercise, and 3) 1-hour of aerobic exercise. Each of these interventions were separated by 1-week. N=8 participants were randomized into performing these interventions in the order of rest-aerobic-resistance and n=8 participants in the order of rest-resistance-aerobic.

Arm/Group Title	Rest, Then Aerobic Exercise, and Then Resistance Exercise Order	Rest-Resistance-Aerobic Order
Arm/Group Description	Rest: 40 minutes of quiet rest in semi-recumbent position Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak) Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise Participant performed interventions in order of rest, then aerobic exercise, then resistance exercise.	Rest: 40 minutes of quiet rest in semi-recumbent position Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak) Participant performed interventions in order of rest, then resistance exercise, then aerobic exercise.
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	7
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak) Rest: 40 minutes of quiet rest in semi-recumbent position
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (6.3)
Sex: Female, Male (Count of Participants)
Female	15 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 53.3%
White	7 46.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Oral Glucose Insulin Sensitivity (OGIS) Index
Description	Oral Glucose Insulin Sensitivity (OGIS) during a 2-hour oral glucose tolerance test. OGIS (an acronym for Oral Glucose Insulin Sensitivity) is a method for the assessment of insulin sensitivity from the oral glucose tolerance test. OGIS provides an index which is analogous to the index of insulin sensitivity obtained from the glucose clamp. Mari, et al. OGIS uses modeling of glucose values at 0, 90, 120 min and insulin values at 0 and 90 min (2-h OGTT) to calculate the index. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 2001 Mar;24(3):539-48. The formula for OGIS is the following: (glucose clearance rate + square root(glucose clearance rate*glucose clearance rate + 4*pp5*pp6(glucose at 90 min-gcl)*330))/2. A calculation spreadsheet for OGIS is found at: http://webmet.pd.cnr.it/ogis/index.php
Time Frame	2 hours post-intervention, up to approximately 3 hours

Outcome Measure Data

Analysis Population Description

Participants completed all interventions but in different order

Arm/Group Title	Acute Aerobic Exercise	Acute Resistance Exercise	Acute Rest
Arm/Group Description	Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak)	Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise	1-hour of sitting rest
Measure Participants	15	15	15
Mean (Standard Deviation) [uU/mL]	405.0 (56.9)	426.0 (53.9)	418.9 (67.0)

2. Primary Outcome

Title	Percent Change in Endothelial Function
Description	Augmentation index: reactive hyperemic response post-blood pressure cuff inflation. Reactive hyperemia is the transient increase in organ blood flow that occurs following a brief period of ischemia (e.g., arterial occlusion).
Time Frame	baseline and immediately post-intervention, approximately 40 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Resistance Exercise	Acute Aerobic Exercise	Acute Rest
Arm/Group Description	One acute exercise session of 40 minutes of resistance exercise Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise	One acute session of 40 minutes of aerobic exercise Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak)	One session of 40 minutes of quiet rest Rest: 40 minutes of quiet rest in semi-recumbent position
Measure Participants	15	15	15
Mean (Standard Deviation) [percent change]	19.2 (11.0)	20.3 (8.0)	16.1 (7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Acute Aerobic Exercise, Acute Resistance Exercise, Acute Rest
	Comments	Repeated measures linear regression
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments

Adverse Events

Time Frame	Approximately 3 hours after each intervention.
Arm/Group Title	Acute Resistance Exercise		Acute Aerobic Exercise		Acute Resting Session
Arm/Group Description	One acute exercise session of 40 minutes of resistance exercise Resistance exercise: One acute exercise session of resistance exercise (40 minutes including 3 sets of 8-10 repetitions at the participant's 10 repetition maximum load of upper and lower extremity exercise		One acute session of 40 minutes of aerobic exercise Aerobic Exercise: One acute session of aerobic exercise (40 minutes of cycle ergometry exercise at 70% of VO2peak)		One session of 40 minutes of quiet rest Rest: 40 minutes of quiet rest in semi-recumbent position
All Cause Mortality
	Acute Resistance Exercise		Acute Aerobic Exercise		Acute Resting Session
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Acute Resistance Exercise		Acute Aerobic Exercise		Acute Resting Session
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Acute Resistance Exercise		Acute Aerobic Exercise		Acute Resting Session
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.