Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum (Quetiapine)

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: NCT02978534
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : December 1, 2016
Sponsor:
Information provided by (Responsible Party):
Crystal Clark, Northwestern University

Brief Summary:
The widespread and common use of quetiapine in childbearing and pregnant women demands more data to inform dosing and toxicity in pregnancy. The new FDA Pregnancy and Lactation Labeling Final Rule (PLLR) will go into effect on June 30th, 2015 and will replace the prior A, B, C, D, and X categories. Additionally, the PLLR will require information to aid prescribing decisions in three categories 1) Pregnancy (including labor and delivery), 2) Lactation, and 3) Females and Males of Reproductive Potential. The pregnancy category will include a subsection that will describe pharmacokinetic and pharmacodynamic characteristics of the medication in pregnancy, fetal risk, and data quality. The data collected in this study will update the FDA pregnancy pharmacokinetic section for quetiapine and inform physicians that prescribe to childbearing women.

Condition or disease Intervention/treatment
Bipolar Disorder Drug: Quetiapine

Detailed Description:

Bipolar Disorder (BD) and Schizophrenia (SCHZ) in pregnancy are associated with pregnancy complications and increased maternal mortality due to physiological and psychosocial changes independent of SGA use. Untreated BD and SCHZ have been associated with an increased risk of placental abnormalities, antepartum hemorrhage, preterm birth, pre-eclampsia, low birth-weight, intrauterine growth retardation, small for gestational age, fetal distress, neonatal hypoglycemia, stillbirth and congenital defects, and the potential for adverse neurodevelopmental outcomes. Severe maternal stress in pregnancy increases the risk for offspring mental disorders, and eye, ear, respiratory, digestive, skin, musculoskeletal, and genitourinary diseases and congenital malformations (i.e., cleft palate, cleft lip). Also, BD and SCHZ illness symptoms are linked to psychosocial consequences that result in poor perinatal outcomes including impulsivity that leads to reckless behavior such as increased indiscriminate sex and exposure to sexually transmitted infections, smoking, increased alcohol and drug use, less prenatal care, and poor nutrition. Furthermore, women with recurrence of mental illness in the perinatal period have increased risk for suicide, a leading cause of maternal death.

The only published case of quetiapine plasma concentrations in a pregnant woman included cross-sectional levels of a woman on 300 mg of quetiapine across pregnancy and postpartum. Compared to six months postpartum, the area under the curve decreased by 27%, 42%, and 18% in the first, second, and third trimester, respectively. Given the complexity of the metabolism of quetiapine to a very active metabolite, it is important to understand the altered metabolism of quetiapine and its active metabolite in pregnancy and the implication for dosing adjustments.

This study will investigate the longitudinal pharmacokinetics of quetiapine in pregnancy, delivery, and postpartum. The long-term goal of this line of research is to establish psychotropic medication dosing algorithms informed by longitudinal pharmacokinetic data to improve mental health and pregnancy outcomes for mothers with serious mental illness.

The primary aims are: 1) Determine the elimination clearance of quetiapine and its major active metabolite, 7-N-desalkyquetiapine, across pregnancy and postpartum; 2) Determine the effect of pharmacokinetic changes on symptoms and toxicity during pregnancy and postpartum, and; 3) Examine the maternal-to-cord plasma concentrations ratios of quetiapine and its major active metabolite, 7-N-desalkylquetiapine.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 12 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum
Study Start Date : March 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Quetiapine
Patients taking quetiapine during pregnancy are eligible to participate in the study. Their dose and plasma concentration levels of quetiapine will be monitored throughout pregnancy and up to three months postpartum.
Drug: Quetiapine
Quetiapine concentrations will be observed in women who have already (under the guidance of a physician) decided to continue taking Quetiapine for the treatment of Bipolar Disorder (any subtype) or Schizophrenia during pregnancy.
Other Name: Seroquel




Primary Outcome Measures :
  1. Change in plasma concentration/elimination [ Time Frame: 2 timepoints during pregnancy (second and third trimesters), and at four and twelve weeks postpartum ]
    For patients taking the immediate release formulation, plasma levels will be obtained beginning at time 0 and at hours, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16. For patients on the extended release formulation, plasma levels will be obtained at time 0 and at hours 0.5, 1, 1.5, 2, 2,5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, and 24.


Secondary Outcome Measures :
  1. Arterial and Venous Umbilical Cord Concentration of Quetiapine and 7-N-desalylquetiapine [ Time Frame: 30 minutes ]
    Arterial and venous cord blood samples will be obtained immediately post-delivery and banked for later analysis

  2. Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations [ Time Frame: CSF to be obtained within 10 minutes of the epidural placement during labor ]
  3. Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum ]
    To determine if there is a pattern of increasing scores on self-report depression assessment (IDS-SR) and declining plasma levels. Increasing scores indicate worsening symptoms or depression episode recurrence.

  4. Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum ]
    To determine if there is a pattern of increasing scores on GAD-7 and declining plasma levels

  5. Scores on mania assessment, Young Mania Reporting Scale (YMRS) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining plasma levels

  6. Scores on Brief Psychosis Rating Scale (BPRS) [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    assessment to evaluate psychotic symptoms

  7. Positive responses on SAFTEE [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    surveys general and specific side effects including somatic, behavioral, and affective symptoms

  8. Delivery outcomes as determined by the Peripartum Events Scale (PES) [ Time Frame: 4 and 12 weeks postpartum ]
    assessment to quantify stressful events related to delivery.

  9. Scores on the seperate domains of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health [ Time Frame: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum. ]
    Assesses patient perceptions in 5 domains:physical function, pain, emotional distress, social function, and fatigue.


Biospecimen Retention:   Samples Without DNA

Blood serum specimen will be obtained to measure quetiapine and estradiol levels. Standard of care labs will be obtained on every participant that is eligible and signs informed consent. Participants will not have more than 50 ml of blood drawn every 8 weeks. Participants will also have the option to have blood drawn for DNA banking.

Participants in the study that elect to receive analgesia for pain related to labor and have a spinal-epidural at Northwestern University will have CSF stored and banked for future analysis.



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 to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women taking quetiapine for the purpose of mood stabilizing will be recruited broadly from Northwestern clinical services, including Internal Medicine, OB/GYN, Family Medicine, and Psychiatry, registries, and from the local Chicagoland community. Patients that sign consent, complete the evaluation and meet criteria will be enrolled into the study.
Criteria

Inclusion Criteria:

  • Age 18-45 years
  • Pregnant, second trimester
  • English-speaking
  • DSM-V diagnosis of Bipolar Disorder or Schizophrenia, any subtype
  • Medically healthy
  • Singleton gestation

Exclusion Criteria:

  • Chronic use of drugs for medical disorders, except thyroid replacement for stable hypothyroidism
  • No psychiatrist or obstetrician
  • QIDS-SR 16 positive answer 3 on item 12, "I have made specific plans for suicide or have actually tried to take my life" within the past week
  • DSM-V diagnosis of substance abuse or dependence in last 6 months, with the exception of cannabis; positive urine drug screen

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): NCT02978534


Contacts
Layout table for location contacts
Contact: Rebecca L Newmark, BA 312-695-6010 rebecca.newmark@northwestern.edu
Contact: Crystal T Clark, MD, MSc 312-695-8648 crystal.clark@northwestern.edu

Locations
Layout table for location information
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Crystal Clark, MD, MSc    312-695-5060    crystal.clark@northwestern.edu   
Contact: Rebecca Newmark, BA    3126956010    rebecca.newmark@northwestern.edu   
Sponsors and Collaborators
Northwestern University
Investigators
Layout table for investigator information
Principal Investigator: Crystal T Clak, MD, MSc Northwestern University

Layout table for additonal information
Responsible Party: Crystal Clark, Assistant Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT02978534     History of Changes
Other Study ID Numbers: 00201540
First Posted: December 1, 2016    Key Record Dates
Last Update Posted: December 1, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Crystal Clark, Northwestern University:
pregnant
quetiapine
bipolar
women
female
postpartum
seroquel
perinatal
manic-depressive
Additional relevant MeSH terms:
Layout table for MeSH terms
Bipolar Disorder
Bipolar and Related Disorders
Mental Disorders
Quetiapine Fumarate
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs