Effects of High Altitude on AMPK Activation

NCT ID: NCT02391519

Last Updated: 2024-06-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

84 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-01-31

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Pregnancy IUGR Preeclampsia

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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).

Collection of myometrial, cord blood, and placental tissue samples

Intervention Type 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).

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).

Collection of myometrial, cord blood, and placental tissue samples

Intervention Type 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).

Interventions

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Collection of myometrial, cord blood, and placental tissue samples

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).

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lorna Moore, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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University of Colorado Denver Anschutz Medical Campus

Aurora, Colorado, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lorna Moore, PhD

Role: CONTACT

303-724-7474

References

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

Reference Type BACKGROUND
PMID: 23941526 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7559250 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11844192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18579652 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10329872 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7124861 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9224184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12700368 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10843906 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20817142 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20610807 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9260988 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9124465 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9399724 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1448242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15383106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7559213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12433660 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16990457 (View on PubMed)

Other Identifiers

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14-2178

Identifier Type: -

Identifier Source: org_study_id

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