The Endocannabinoid System in Human Gestational Tissues in Labor

NCT03752021 | Completed

• 1 other identifier: IRB00051905
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to determine if the endocannabinoid (a biological system) plays a role in the labor process.

Conditions

Labor

Keywords

Endocannabinoid System; Human Gestational Tissues; Labor; Cesarean Section

Outcome Measures

Primary Outcomes (6)

• Presence of CB1 receptor protein

  Identification of CB1 receptor protein interacting protein (CRIP) in gestational membranes, placenta, and myometrium

  At the time of C-section

• Presence of CB2 receptor protein

  Identification of CB2 receptor protein interacting protein (CRIP) in gestational membranes, placenta, and myometrium

  At the time of C-section

• Presence of cannabinoid receptor

  Identification of cannabinoid receptor interacting protein (CRIP) in gestational membranes, placenta, and myometrium

  At the time of C-section

• Levels of CB1 receptor protein

  Quantification of levels of CB1 receptor protein interacting protein (CRIP) in gestational membranes, placenta, and myometrium. A statistical comparison between groups will be performed.

  At the time of C-section

• Levels of CB2 receptor protein

  Quantification of CB2 receptor protein interacting protein (CRIP) in gestational membranes, placenta, and myometrium. A statistical comparison between groups will be performed.

  At the time of C-section

• Levels of cannabinoid receptor

  Quantification of cannabinoid receptor interacting protein (CRIP) in gestational membranes, placenta, and myometrium. A statistical comparison between groups will be performed.

  At the time of C-section

Study Arms (2)

Laboring Subjects

Subjects with a planned cesarean delivery who labor prior to their scheduled date or those who are in labor and require an unplanned but non-emergent cesarean delivery. These subjects will be approached upon admission to the study facility by the researcher for potential enrollment to allow adequate time to consider participation, ask questions, provide consent, and prior to procedure (Myometrial Sampling).

Procedure: Myometrial Sampling

Non Laboring Subjects

Subjects with a planned cesarean delivery will be approached by the researcher during prenatal visits or at the study facilities prior to planned procedure (Myometrial Sampling)

Procedure: Myometrial Sampling

Interventions

Myometrial Sampling PROCEDURE

A myometrial sample will be obtained at the time of cesarean delivery. Sample will be obtained from the superior edge of the existing lower uterine segment incision and will be 2 inches in length and 0.5 inches in width. The uterine incision will be repaired in a standard two-layer closure. If a classical cesarean (vertical) uterine incision is deemed necessary and is performed by the surgical team, a sample of the same size will be taken parallel to the incision at the existing edge. The classical uterine incision will be closed utilizing the standard layered technique. Placenta and gestational membrane tissue will be obtained after placental delivery. The entire placenta and attached gestational membranes will be collected if not being sent for pathologic review

Laboring Subjects; Non Laboring Subjects

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* A total of 20 subjects will be enrolled in the pilot study * 10 laboring subjects * 10 non-laboring subjects

You may qualify if:

• Pregnant women ages \> 18 years old
• Pregnant women 22 weeks, 0 days through 42 weeks, 0 days gestation undergoing cesarean section
• Singleton gestation

You may not qualify if:

• Cannabinoid use during pregnancy
• Illicit drug use during pregnancy
• Nonsteroidal anti-inflammatory drug use within 7 days of cesarean section
• Maternal comorbidities including pre-existing diabetes, pre-existing hypertension, hypertensive disorders of pregnancy (preeclampsia, eclampsia), epilepsy currently being treated with antiepileptic medication, intraamniotic infection
• Uterine abnormalities
• Fetal anomalies
• Drug use or dependency

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (2)

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (20)

• Navathe R, Berghella V. Tocolysis for Acute Preterm Labor: Where Have We Been, Where Are We Now, and Where are We Going? Am J Perinatol. 2016 Feb;33(3):229-35. doi: 10.1055/s-0035-1571147. Epub 2016 Jan 25.

  PMID: 26808195 BACKGROUND

• Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4.

  PMID: 18177778 BACKGROUND

• Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990 Aug 9;346(6284):561-4. doi: 10.1038/346561a0.

  PMID: 2165569 BACKGROUND

• Howlett AC, Bidaut-Russell M, Devane WA, Melvin LS, Johnson MR, Herkenham M. The cannabinoid receptor: biochemical, anatomical and behavioral characterization. Trends Neurosci. 1990 Oct;13(10):420-3. doi: 10.1016/0166-2236(90)90124-s.

  PMID: 1700516 BACKGROUND

• Paria BC, Song H, Wang X, Schmid PC, Krebsbach RJ, Schmid HH, Bonner TI, Zimmer A, Dey SK. Dysregulated cannabinoid signaling disrupts uterine receptivity for embryo implantation. J Biol Chem. 2001 Jun 8;276(23):20523-8. doi: 10.1074/jbc.M100679200. Epub 2001 Mar 8.

  PMID: 11279117 BACKGROUND

• Paria BC, Dey SK. Ligand-receptor signaling with endocannabinoids in preimplantation embryo development and implantation. Chem Phys Lipids. 2000 Nov;108(1-2):211-20. doi: 10.1016/s0009-3084(00)00197-3.

  PMID: 11106792 BACKGROUND

• Das SK, Paria BC, Chakraborty I, Dey SK. Cannabinoid ligand-receptor signaling in the mouse uterus. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4332-6. doi: 10.1073/pnas.92.10.4332.

  PMID: 7753807 BACKGROUND

• Schmid PC, Paria BC, Krebsbach RJ, Schmid HH, Dey SK. Changes in anandamide levels in mouse uterus are associated with uterine receptivity for embryo implantation. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4188-92. doi: 10.1073/pnas.94.8.4188.

  PMID: 9108127 BACKGROUND

• Paria BC, Wang H, Dey SK. Endocannabinoid signaling in synchronizing embryo development and uterine receptivity for implantation. Chem Phys Lipids. 2002 Dec 31;121(1-2):201-10. doi: 10.1016/s0009-3084(02)00156-1.

  PMID: 12505701 BACKGROUND

• Dennedy MC, Friel AM, Houlihan DD, Broderick VM, Smith T, Morrison JJ. Cannabinoids and the human uterus during pregnancy. Am J Obstet Gynecol. 2004 Jan;190(1):2-9; discussion 3A. doi: 10.1016/j.ajog.2003.07.013.

  PMID: 14749627 BACKGROUND

• Park B, Gibbons HM, Mitchell MD, Glassa M. Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta. Placenta. 2003 May;24(5):473-8. doi: 10.1053/plac.2002.0926.

  PMID: 12744923 BACKGROUND

• Wang H, Xie H, Dey SK. Loss of cannabinoid receptor CB1 induces preterm birth. PLoS One. 2008 Oct 3;3(10):e3320. doi: 10.1371/journal.pone.0003320.

  PMID: 18833324 BACKGROUND

• Habayeb OM, Taylor AH, Evans MD, Cooke MS, Taylor DJ, Bell SC, Konje JC. Plasma levels of the endocannabinoid anandamide in women--a potential role in pregnancy maintenance and labor? J Clin Endocrinol Metab. 2004 Nov;89(11):5482-7. doi: 10.1210/jc.2004-0681.

  PMID: 15531501 BACKGROUND

• Costa MA, Fonseca BM, Keating E, Teixeira NA, Correia-da-Silva G. 2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells. Reproduction. 2014 Feb 3;147(3):301-11. doi: 10.1530/REP-13-0563. Print 2014 Mar.

  PMID: 24324206 BACKGROUND

• Chiossi G, Costantine MM, Bytautiene E, Kechichian T, Hankins GD, Sbrana E, Saade GR, Longo M. The effects of prostaglandin E1 and prostaglandin E2 on in vitro myometrial contractility and uterine structure. Am J Perinatol. 2012 Sep;29(8):615-22. doi: 10.1055/s-0032-1311986. Epub 2012 May 25.

  PMID: 22639355 BACKGROUND

• Chioss G, Costantine MM, Bytautiene E, Betancourt A, Hankins GD, Saade GR, Longo M. In vitro myometrial contractility profiles of different pharmacological agents used for induction of labor. Am J Perinatol. 2012 Oct;29(9):699-704. doi: 10.1055/s-0032-1314891. Epub 2012 May 29.

  PMID: 22644831 BACKGROUND

• Luckas MJ, Wray S. A comparison of the contractile properties of human myometrium obtained from the upper and lower uterine segments. BJOG. 2000 Oct;107(10):1309-11. doi: 10.1111/j.1471-0528.2000.tb11626.x.

  PMID: 11028587 BACKGROUND

• Moynihan AT, Smith TJ, Morrison JJ. The relaxant effect of nifedipine in human uterine smooth muscle and the BK(Ca) channel. Am J Obstet Gynecol. 2008 Feb;198(2):237.e1-8. doi: 10.1016/j.ajog.2007.08.074.

  PMID: 18226634 BACKGROUND

• Quenby S, Matthew A, Zhang J, Dawood F, Wray S. In vitro myometrial contractility reflects indication for caesarean section. BJOG. 2011 Nov;118(12):1499-506. doi: 10.1111/j.1471-0528.2011.03064.x. Epub 2011 Jul 27.

  PMID: 21790954 BACKGROUND

• Kozakiewicz ML, Zhang J, Leone-Kabler S, Yamaleyeva LM, McDonald AG, Brost BC, Howlett AC. Differential Expression of CB1 Cannabinoid Receptor and Cannabinoid Receptor Interacting Protein 1a in Labor. Cannabis Cannabinoid Res. 2022 Jun;7(3):279-288. doi: 10.1089/can.2020.0107. Epub 2021 Apr 16.

  PMID: 33998898 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

A sample of the uterus will be removed at the existing incision made by your doctors. The uterine segment (sample) will be 2 inches in length and 0.5 inches in width. The placenta and the attached membranes will also be collected for the study. The uterine incision will be repaired in the standard fashion.

Study Officials

• Melissa L Kozakiewicz, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: November 23, 2018
• Study Start: January 25, 2019
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: August 15, 2019

Record last verified: 2019-06

Locations

US (2)