How Pregnant Women and Their Babies Metabolize Ondansetron Compared to a Group of Non-pregnant Women (Zofran_PK)

May 28, 2015 updated by: David R. Drover, Stanford University

Prevention of Neonatal Abstinence Syndrome

This is called "Aim 1" of the investigators' NIH grant. Ondansetron (Zofran) is a safe and effective drug used in pregnant women to prevent nausea but the investigators do not know what effect pregnancy may have on the metabolism of Zofran in pregnant women or their babies. Therefore the investigators will enroll approximately 40 pregnant women and their babies and draw blood samples from the mother, the baby and the cord, to determine how much Zofran is in each sample of blood (called the pharmacokinetics or PK of Zofran). The pregnant women will receive Zofran, as a standard-of-care drug, for their scheduled Cesarean Section.

The investigators will also enroll about 20 non-pregnant women undergoing surgery who will receive Zofran as standard-of-care during surgery. In both the pregnant & the non-pregnant women, the investigators will draw blood samples at the same time points based on number of minutes from the time the Zofran is given. The blood data (PK of Zofran) will help the investigators move into Aim 2 of the study, which will be done in pregnant, narcotic-addicted mothers and their babies who are born addicted to narcotics. Aim 2 will be listed separately as it will be an interventional study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This phase of the study is Aim 1 and it will lead to Aim 2, which specifically will address the Prevention of Neonatal Abstinence Syndrome (NAS).

NAS is a constellation of narcotic drug withdrawal symptoms that develops in 42-94% of the infants born to narcotic dependent mothers. This severe syndrome, of which there are no preventative treatments, can result in prolonged hospitalization, some of which may be in the neonatal intensive care unit (NICU). The investigators have shown that ondansetron can eliminate or alleviate the symptoms of narcotic drug withdrawal in experimental studies in mice and in humans. Based upon these results, it is quite possible that ondansetron administration to pregnant narcotic-using mothers just prior to delivery, followed by a 3-day period of ondansetron administration to the neonate, could reduce the incidence or severity of NAS symptoms.

AIM 1 is a pharmacokinetic (PK) study of intravenous (IV) ondansetron in three different groups of participants: Study Group #1 = non-pregnant women undergoing surgery; Study Group #2 = pregnant women scheduled for cesarean section delivery; Study Group #3 = viable, full term, singleton neonates born to study group #2 mothers. Group #1 will be given IV ondansetron prior to their surgery and up to 5 PK blood samples will be drawn from an indwelling IV line or by IV stick. The PK samples will be 2-5 ml each and will be drawn at baseline (prior to ondansetron) and then at 7, 15, and 40 min and 8 hours after the ondansetron. Group #2 will be given IV ondansetron prior to their cesarean section and up to 6 PK blood samples will be drawn from an indwelling IV line or by IV stick. The PK samples will be 2-5 ml each and will be drawn at baseline, 7, 15, 40 min and prior to delivery and 8 hours after the ondansetron is given. The Group #3 neonates will provide a section of the umbilical cord from which arterial and venous blood samples will be drawn (this section of cord would normally be thrown out and the parents are consenting to allow the Investigators to take these two samples). Each time the baby has a "Standard-of-Care" lab test ordered by heel stick or needle stick, the investigators will obtain a few drops of blood to place on the special research filter paper to determine how much ondansetron is in the baby's blood. If the parents will allow any extra heel sticks, the Investigators will try to obtain 1-2 samples of blood in the first 6 hours of life. If the parents only want their baby's blood taken at the standard-of-care lab draws, then the first scheduled lab draw is at 24 hours of life for the newborn screening which is a mandated by state law. All blood samples taken for this study are being processed by the investigator, not the Stanford Lab. Also, the investigators are doing the PK analysis of the dried blood spots on the filter paper and the analysis of the frozen plasma samples.

Aim 2 of this NIH grant will be entered separately into ClinicalTrials.gov. It will be a multi-center, randomized, double-blind, placebo-controlled trial to determine whether ondansetron treatment will reduce the incidence or severity of NAS in babies born to narcotic-using mothers.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Lucile Packard Children's Hospital & Stanford Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

For Non-pregnant Females (Group #1)

  1. Age 18-45 yrs inclusive
  2. Generally healthy
  3. Undergoing any scheduled surgical procedure deemed suitable by the Investigator MD
  4. Planned to receive the drug Ondansetron for the surgery
  5. Able and willing to sign the informed consent

For Pregnant Females (Group #2)

  1. Age 18-45 yrs inclusive
  2. Term pregnancy (37 weeks through 41 wks + 6 days)
  3. Generally healthy (not morbidly obese)
  4. Undergoing a planned C-section or by an unplanned, non-urgent C-section
  5. Planned to receive the drug Ondansetron for the surgery
  6. Single birth
  7. Able and willing to sign the informed consent for herself & the baby

For the Neonatal Participant (Group #3)

  1. Male or female
  2. Viable birth
  3. Gestational age of 37 weeks through 41 weeks + 6 days
  4. Mother gave written consent for baby to participate

Exclusion Criteria:

  1. Medical condition that would effect the metabolism of ondansetron
  2. Known allergy to ondansetron
  3. Use of medications in the last 48 hours, by the pregnant or non-pregnant subjects, that might induce or inhibit the metabolism of ondansetron (such as CYP3A4 inhibitors or inducers)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Pregnant women
Full term pregnant women scheduled for Cesarean section and will be given Ondansetron as standard-of-care prior to surgery.
Drug: Ondansetron
Pregnant & non-pregnant women will receive either 4mg or 8mg of Ondansetron (IV) once prior to surgical procedure (open-label). Women are in the study for 8 hours. Babies of pregnant women are not given Ondansetron but are in the study for 24-48 hours.
Other Names:
  • Zofran
ACTIVE_COMPARATOR: Non-pregnant women
Non-pregnant women scheduled for surgery at Stanford who will be given Ondansetron prior to their surgery as standard-of-care.
Drug: Ondansetron
Pregnant & non-pregnant women will receive either 4mg or 8mg of Ondansetron (IV) once prior to surgical procedure (open-label). Women are in the study for 8 hours. Babies of pregnant women are not given Ondansetron but are in the study for 24-48 hours.
Other Names:
  • Zofran
NO_INTERVENTION: Neonates
Babies of the pregnant women enrolled in the study; no ondansetron is given to babies in this "Aim 1" of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume of Distribution Estimated Pharmacokinetic Parameter
Time Frame: 8 hours for women; 48 hours for neonate.
This is an estimated pharmacokinetic parameter as calculated by NONMEM.
8 hours for women; 48 hours for neonate.
Metabolic Clearance of Ondasetron
Time Frame: 8 hours for women; 48 hours for neonate.
This is a mathematical estimation of the clearance for ondasetron as calculated by NONMEM.
8 hours for women; 48 hours for neonate.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: David R. Drover, MD, Stanford University School of Medicine, Department of Anesthesia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (ACTUAL)

May 1, 2013

Study Completion (ACTUAL)

May 1, 2013

Study Registration Dates

First Submitted

January 28, 2013

First Submitted That Met QC Criteria

February 26, 2013

First Posted (ESTIMATE)

February 28, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

June 1, 2015

Last Update Submitted That Met QC Criteria

May 28, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1R01HD070795-01A1 (NIH)
  • NAS Aim 1 (OTHER: Stanford)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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