Effects of High Altitude on AMPK Activation

NCT02391519 | Recruiting

• 1 other identifier: 14-2178
• Study Type: observational
• Target: 84
• Locations: 1 country
• Sites: 1

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.

Conditions

IUGR; Preeclampsia; Pregnancy

Keywords

Pregnancy; High altitude; vasoreactivity; myometrial arteries

Outcome Measures

Primary Outcomes (1)

• Changes in Myometrial artery dimensions

  Myometrial artery dimensions as quantified by immunohistochemistry or other staining techniques, and results of studies of isolated myometrial artery studies in which vasoconstrictor and vasodilator responses to pharmacological agonists are measured using absolute values and the percent maximal contraction to potassium chloride.

  Up to 1 year

Study Arms (2)

High Altitude (3000 m)

Collection of 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).

Procedure: Collection of myometrial, cord blood, and placental tissue samples

Low Altitude (1600 m)

Collection of 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).

Procedure: Collection of myometrial, cord blood, and placental tissue samples

Interventions

Collection of myometrial, cord blood, and placental tissue samples PROCEDURE

We 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).

High Altitude (3000 m); Low Altitude (1600 m)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Denver Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (19)

• Osol G, Moore LG. Maternal uterine vascular remodeling during pregnancy. Microcirculation. 2014 Jan;21(1):38-47. doi: 10.1111/micc.12080.

  PMID: 23941526 BACKGROUND

• Zamudio S, Palmer SK, Droma T, Stamm E, Coffin C, Moore LG. Effect of altitude on uterine artery blood flow during normal pregnancy. J Appl Physiol (1985). 1995 Jul;79(1):7-14. doi: 10.1152/jappl.1995.79.1.7.

  PMID: 7559250 BACKGROUND

• 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.

  PMID: 11844192 BACKGROUND

• 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.

  PMID: 18579652 BACKGROUND

• 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.

  PMID: 10329872 BACKGROUND

• Moore LG, Hershey DW, Jahnigen D, Bowes W Jr. The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude. Am J Obstet Gynecol. 1982 Oct 15;144(4):423-9. doi: 10.1016/0002-9378(82)90248-4.

  PMID: 7124861 BACKGROUND

• Jensen GM, Moore LG. The effect of high altitude and other risk factors on birthweight: independent or interactive effects? Am J Public Health. 1997 Jun;87(6):1003-7. doi: 10.2105/ajph.87.6.1003.

  PMID: 9224184 BACKGROUND

• Keyes LE, Armaza JF, Niermeyer S, Vargas E, Young DA, Moore LG. Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediatr Res. 2003 Jul;54(1):20-5. doi: 10.1203/01.PDR.0000069846.64389.DC. Epub 2003 Apr 16.

  PMID: 12700368 BACKGROUND

• White MM, McCullough RE, Dyckes R, Robertson AD, Moore LG. Chronic hypoxia, pregnancy, and endothelium-mediated relaxation in guinea pig uterine and thoracic arteries. Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H2069-75. doi: 10.1152/ajpheart.2000.278.6.H2069.

  PMID: 10843906 BACKGROUND

• Xiao D, Longo LD, Zhang L. Role of KATP and L-type Ca2+ channel activities in regulation of ovine uterine vascular contractility: effect of pregnancy and chronic hypoxia. Am J Obstet Gynecol. 2010 Dec;203(6):596.e6-12. doi: 10.1016/j.ajog.2010.07.038.

  PMID: 20817142 BACKGROUND

• Luksha L, Luksha N, Kublickas M, Nisell H, Kublickiene K. Diverse mechanisms of endothelium-derived hyperpolarizing factor-mediated dilatation in small myometrial arteries in normal human pregnancy and preeclampsia. Biol Reprod. 2010 Nov;83(5):728-35. doi: 10.1095/biolreprod.110.084426. Epub 2010 Jul 7.

  PMID: 20610807 BACKGROUND

• Cockell AP, Poston L. Flow-mediated vasodilatation is enhanced in normal pregnancy but reduced in preeclampsia. Hypertension. 1997 Aug;30(2 Pt 1):247-51. doi: 10.1161/01.hyp.30.2.247.

  PMID: 9260988 BACKGROUND

• Sladek SM, Magness RR, Conrad KP. Nitric oxide and pregnancy. Am J Physiol. 1997 Feb;272(2 Pt 2):R441-63. doi: 10.1152/ajpregu.1997.272.2.R441.

  PMID: 9124465 BACKGROUND

• Clapp JF 3rd, Capeless E. Cardiovascular function before, during, and after the first and subsequent pregnancies. Am J Cardiol. 1997 Dec 1;80(11):1469-73. doi: 10.1016/s0002-9149(97)00738-8.

  PMID: 9399724 BACKGROUND

• Palmer SK, Zamudio S, Coffin C, Parker S, Stamm E, Moore LG. Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol. 1992 Dec;80(6):1000-6.

  PMID: 1448242 BACKGROUND

• Kametas NA, McAuliffe F, Krampl E, Chambers J, Nicolaides KH. Maternal cardiac function during pregnancy at high altitude. BJOG. 2004 Oct;111(10):1051-8. doi: 10.1111/j.1471-0528.2004.00246.x.

  PMID: 15383106 BACKGROUND

• Zamudio S, Palmer SK, Dahms TE, Berman JC, Young DA, Moore LG. Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude. J Appl Physiol (1985). 1995 Jul;79(1):15-22. doi: 10.1152/jappl.1995.79.1.15.

  PMID: 7559213 BACKGROUND

• Mateev S, Sillau AH, Mouser R, McCullough RE, White MM, Young DA, Moore LG. Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow. Am J Physiol Heart Circ Physiol. 2003 Mar;284(3):H820-9. doi: 10.1152/ajpheart.00701.2002. Epub 2002 Nov 14.

  PMID: 12433660 BACKGROUND

• Wang X, Proud CG. The mTOR pathway in the control of protein synthesis. Physiology (Bethesda). 2006 Oct;21:362-9. doi: 10.1152/physiol.00024.2006.

  PMID: 16990457 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Myometrial tissue, Cord Blood, Placental Tissue.

MeSH Terms

Conditions

Pre-Eclampsia; Altitude Sickness

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Respiration Disorders; Respiratory Tract Diseases

Study Officials

• Lorna Moore, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorna Moore, PhD

CONTACT

303-724-7474; lorna.moore@ucdenver.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 18, 2015
• Study Start: January 1, 2016
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

US (1)