Clinical trial NCT02391519: Effects of High Altitude on AMPK Activation
Official title: Effects of High Altitude on 5' Adenosine Monophosphate-activated Protein Kinase (AMPK) Activation and Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Regulation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pregnancy
IUGR
Preeclampsia
Keywords: Pregnancy
High altitude
vasoreactivity
myometrial arteries
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2015-03-18
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women scheduled for cesarean delivery at University of Colorado Hospital (Denver, 1600 m) and St. Anthony's Summit Medical Center (Summit County, 3000 m) will be identified. In order to avoid any possible confounding effects of labor or prematurity, only women with elective cesarean deliveries will be approached for enrollment (cesarean delivery at a prescheduled time without any labor, typically at 39 weeks gestation).

Brief summary: Pregnancy elicits adaptive changes in uteroplacental blood flow, which are altered at high altitude and may contribute to the observed 3-fold increase in intrauterine growth restriction (IUGR) and preeclampsia (PreE). The investigators propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

Detailed description: The Investigators will determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries. This will be novel information regarding pregnancy at altitude and of significance not just for women and families in Colorado, but also at high-altitude locations throughout the world. If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

The Investigators will also determine whether the chronic hypoxia of high altitude alters DNA methylation patterns and expression of key genes involved in metabolic homeostasis in maternal, placental and fetal cells and, in turn, the relationship of these changes to fetal growth and maternal well-being.

Eligibility criteria: Inclusion Criteria:

* Women scheduled for cesarean delivery at University of Colorado Hospital (Denver, 1600 m) and St. Anthony's Summit Medical Center (Summit County, 3000 m)
* Cesarean delivery at a prescheduled time without any labor, typically at 39 weeks gestation

Exclusion Criteria:

* Women will be excluded if there are co-existing medical diagnoses that are known to affect vascular parameters (i.e., diabetes mellitus, gestational diabetes, any hypertensive disorder of pregnancy, or a current smoker).
* Women with multiple gestations and preterm deliveries will also be excluded.

Primary outcomes:
measure: Changes in Myometrial artery dimensions
timeFrame: Up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Lorna Moore, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Osol G, Moore LG. Maternal uterine vascular remodeling during pregnancy. Microcirculation. 2014 Jan;21(1):38-47. doi: 10.1111/micc.12080.
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citation: Krampl ER, Espinoza-Dorado J, Lees CC, Moscoso G, Bland JM, Campbell S. Maternal uterine artery Doppler studies at high altitude and sea level. Ultrasound Obstet Gynecol. 2001 Dec;18(6):578-82. doi: 10.1046/j.0960-7692.2001.00579.x.
citation: Julian CG, Galan HL, Wilson MJ, Desilva W, Cioffi-Ragan D, Schwartz J, Moore LG. Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude. Am J Physiol Regul Integr Comp Physiol. 2008 Sep;295(3):R906-15. doi: 10.1152/ajpregu.00164.2008. Epub 2008 Jun 25.
citation: Palmer SK, Moore LG, Young D, Cregger B, Berman JC, Zamudio S. Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado. Am J Obstet Gynecol. 1999 May;180(5):1161-8. doi: 10.1016/s0002-9378(99)70611-3.
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