Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Influence of in Utero Cannabis Exposure on Neonatal Brain Morphology and Structural Connectivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03718520
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : June 4, 2020
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
University of Colorado, Denver

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Cannabis is the most commonly used drug by women during pregnancy with an estimated prevalence of use in Colorado of 5.7%. THC and its metabolites freely cross the placenta and blood-brain barrier to bind with cannabinoid receptors, disrupting the endogenous cannabinoid signaling system during a critical period of development of cortical circuitry structure and function. The density of cannabinoid receptors in the developing brain is high, especially in the limbic areas and prefrontal lobes. Research in animal models suggests synaptic plasticity in the prefrontal lobes as well the amygdala and hippocampus are impacted by the prenatal cannabis exposure; regions associated with both cognitive and emotional control, thus influencing long-term deficiencies in attention and impulsivity. This pilot study will collect preliminary data on the structural impact of in utero cannabis exposure on region-specific morphology and structural connectivity of white matter tracts that connect to the prefrontal lobes and the limbic regions shortly after birth, before confounding by the postnatal environment becomes a major influence.

Condition or disease Intervention/treatment
Cannabis Use Disorder PREG1 Drug Use Fetal Exposure During Pregnancy Neurodevelopmental Abnormality Other: no intervention, this is a purely observational study

Detailed Description:

Cannabis is the most commonly used psychoactive substance among pregnant women, with an estimated prevalence of use between 5 to 20% in in the United States. Little is known about the neurodevelopmental consequences for the fetus, particularly in the context of contemporary cannabis use patterns including high potency strains, cannabinoids and novel routes of administration. Colorado leads the nation in implementation of legalized medical and retail marijuana. Coupled with a growing pro-marijuana advocacy movement, marijuana may be perceived as "safe" to use during pregnancy. The local actions of endocannabinoids are in place in the placenta during fetal brain development and THC and its metabolites freely pass the placental barrier and the fetal blood-brain barrier. Furthermore, cannabinoid receptors appear to be more widespread in the fetal and neonatal prefrontal cortex (PFC) and the limbic areas (the amygdala and hippocampus) than in the adult brain, thus the in utero period may be a sensitive period of human brain development during which exogenous cannabinoids could permanently alter neurodevelopmental processes. Human epidemiologic studies across diverse populations have reported an emerging theme of deficiencies related to impulse control and executive functioning among offspring with in utero exposure to cannabis starting in adolescence. Only rudimentary aspects of executive function are present in infants, thus evidence of an impact during infancy and the toddler years is sparse, inconsistent and confounded by the postnatal environment (i.e., daycare, caregiver functioning). Research is needed to evaluate the proximal impact of in utero cannabis exposure on robust metrics of neonatal brain morphology and structural integrity of white matter tracts that connect to the PFC and the limbic regions before the influence of postnatal exposures become a major confounding influence.

To address this challenge, a pilot prospective pre-birth cohort study will be conducted to investigate the impact of chronic in utero cannabis exposure by enrolling 110 mother-infant pairs (50 exposed and 60 unexposed controls) for a neonate neuroimaging scan within 2 weeks after birth. Chronic in utero cannabis exposure will be quantified using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS) of neonatal meconium. The associations between in utero cannabis exposure and neural morphological outcomes will be examined by structural MRI and diffusion tensor imaging (DTI). The central hypothesis is that in utero cannabis exposure will be associated with alterations in grey and white matter development in the prefrontal lobe and its connectivity to limbic regions.

Specific Aim 1: To determine the magnitude of the association between in utero exposure to cannabis and neonate brain morphology and structural connectivity.

Hypothesis: In utero exposure to cannabis (assessed by THC metabolites in meconium) will be associated with the following neonate brain structural outcomes: (1) Grey matter: reduced volume in the PFC and limbic regions (i.e. the amygdala, hippocampus); (2) White matter: reduced structural integrity (assessed by fractional anisotropy) of white matter tracts that connect to the PFC and the limbic regions including the uncinate fasciculus and the cingulum bundle. The associations will be independent of other maternal substance use (i.e. tobacco), postnatal feeding practices (i.e. breastfeeding), socio-demographic characteristics and maternal mental health.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 220 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Influence of in Utero Cannabis Exposure on Neonatal Brain Morphology and Structural Connectivity
Actual Study Start Date : November 7, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marijuana

Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort Intervention/treatment
prenatal exposed to cannabis
50 mother-infant pairs with self-reported maternal chronic cannabis use during pregnancy
 Other: no intervention, this is a purely observational study
No intervention
prenatal not-exposed to cannabis
60 mother-infant pairs with no self-reported maternal cannabis use during pregnancy
 Other: no intervention, this is a purely observational study
No intervention


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. region specific grey matter volume (mm^2) in the PFC and limbic regions [ Time Frame: 2 weeks postnatal age ]
    region specific volume (mm^2)

  2. structural integrity measured by fractional anisotrophy of white matter tracks that connect the PFC and limbic regions [ Time Frame: 2 weeks postnatal age ]
    mean fractional anisotrophy


Secondary Outcome Measures :
  1. Negative affectivity based on a subscale from the Infant Behavioral Questionnaire (Rothbart, 1981) [ Time Frame: 1 year postpartum ]
    Four subscales on the IBQ-R will be combined to form a negative affectivity scale including scales of Sadness, Distress to Limitations, Fear, and Falling Reactivity/Rate of Recovery from Distress.


Biospecimen Retention:   Samples Without DNA
Maternal urine at 28-36 weeks gestation; maternal plasma and urine at delivery; neonate urine, meconium, cord blood and cord segment shortly after birth; maternal urine at 2 weeks postpartum; maternal urine at 1 year postpartum

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   This study plans to enroll pregnant women.
Sampling Method:   Non-Probability Sample
Study Population
This will be an observational, pre-birth prospective pilot study of 110 mother-infant pairs (50 with prenatal cannabis exposure and 60 unexposed pairs) who deliver at two academic medical centers in the Denver Metro area of Colorado (Denver Health Medical Center and the University of Colorado Hospital at Anschutz. Unexposed controls will be frequency matched to exposed cases by maternal education level. To isolate the influence of cannabis exposure, mothers using tobacco, alcohol or other drugs during pregnancy will be excluded.
Criteria

Inclusion Criteria:

  • pregnant women who are receiving prenatal care at the University of Colorado Hospital at Anschutz (UCH) or Denver Health Medical Center.
  • maternal positive urine toxicology screen for cannabis at any clinical prenatal visit or self-report of cannabis during pregnancy at a clinical visit
  • greater than ≥ 28 weeks gestation,
  • aged ≥18 years,
  • expecting a singleton birth,
  • live in Colorado, and plan to deliver at UCH or Denver Health Medical Center .
  • Inclusion criteria for unexposed controls will be identical to that of exposed cases with the exception that they cannot have a positive toxicology screen for cannabis or self-reported cannabis use during pregnancy.

Exclusion Criteria (for unexposed cases and controls):

  • use of tobacco, alcohol or other drugs during pregnancy,
  • serious chronic diseases (cancer, psychiatric diseases, steroid-dependent asthma, pre-existent diabetes mellitus of any kind),
  • mothers who subsequently experience a fetal death or deliver a premature infant (< 37 weeks of gestation).
  • Postnatal exclusions will include failure to collect meconium samples at birth, infant neurological trauma, other neurological conditions in the infant (e.g., epilepsy),
  • suspicion of metal in body or other MRI contraindications in either the mother or infant.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03718520


Contacts
Layout table for location contacts
Contact: Tessa Crume, PhD, MSPH 3037244452 tessa.crume@ucdenver.edu

Locations
Layout table for location information
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Jocelyn Phipers, RN, CCRP    303-724-7807    Jocelyn.Phipers@ucdenver.edu   
Sub-Investigator: Jocelyn Phipers, RN, CCRP         
Sub-Investigator: Chistine Conageski, MD         
Denver Health Medical Center Not yet recruiting
Denver, Colorado, United States, 80204
Contact: Beth Kingsley, CRA    303-602-7061    Elizabeth.Kingsley@dhha.org   
Sub-Investigator: Elaine Stickrath, MD         
Sponsors and Collaborators
University of Colorado, Denver
National Institute on Drug Abuse (NIDA)
Investigators
Layout table for investigator information
Principal Investigator: Tessa Crume, PhD, MSPH University of Colorado, Colorado School of Public Health
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03718520    
Other Study ID Numbers: 18-0004
R21DA043833 ( U.S. NIH Grant/Contract )
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: A completely de-identified dataset will be created and may be shared upon PI-agreement ad development of data sharing agreements.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
cannabis
fetal programming
pregnancy
infant neuroimaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Marijuana Abuse
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders