Pharmacokinetics of Quetiapine Across Pregnancy and Postpartum (Quetiapine)
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|ClinicalTrials.gov Identifier: NCT02978534|
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : December 1, 2016
|Condition or disease||Intervention/treatment|
|Bipolar Disorder||Drug: Quetiapine|
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.
|Study Type :||Observational|
|Estimated Enrollment :||12 participants|
|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|
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.
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
- 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.
- 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
- Cerebrospinal Fluid (CSF) Quetiapine and 7-N-desalkyquetiapine Concentrations [ Time Frame: CSF to be obtained within 10 minutes of the epidural placement during labor ]
- 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.
- 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
- 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
- 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
- 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
- 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.
- 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.
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
|Contact: Rebecca L Newmark, BAfirstname.lastname@example.org|
|Contact: Crystal T Clark, MD, MScemail@example.com|
|United States, Illinois|
|Northwestern Memorial Hospital||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Crystal Clark, MD, MSc 312-695-5060 firstname.lastname@example.org|
|Contact: Rebecca Newmark, BA 3126956010 email@example.com|
|Principal Investigator:||Crystal T Clak, MD, MSc||Northwestern University|