Pregnant Women Taking Lamictal for Bipolar Disorder (PK-LAPB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Crystal Clark, Northwestern University
ClinicalTrials.gov Identifier:
NCT01996293
First received: November 15, 2013
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

This study seeks to examine how the dose of lamotrigine (Lamictal) should be adjusted during pregnancy for women with Bipolar Disorder. The investigators predict that the concentration of Lamictal in women's blood will decrease during pregnancy, and increase after postpartum. Because the concentration of the medication is likely to decrease during pregnancy, it is important for doctors to know how much they should increase a patient's dose in order to prevent worsening of Bipolar symptoms. In this study, the investigators will ask that participants complete up to five overnight visits to our clinical research unit where their blood will be drawn every couple of hours, through an IV catheter, to measure how the concentration of lamotrigine (Lamictal) changes over time. Participants will be compensated for their time.


Condition Intervention
Bipolar Disorder
Drug: lamotrigine

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Pharmacokinetics of Lamotrigine in Pregnant and Postpartum Women With Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Serum L/D ratio change [ Time Frame: An average of every 10 weeks; Hours 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    Serum levels will be obtained beginning at time 0 and at hours, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24 and L/D ratio will be determined at each time point. This series of serum levels will be completed an average of every 10 weeks across pregnancy, and postpartum.

  • Area Under the Concentration Curve (AUC 0-24h) [ Time Frame: An average of every 10 weeks; Hours 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24 ] [ Designated as safety issue: No ]
    Serum levels will be obtained beginning at time 0 and at hours, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24 and L/D ratio will be determined at each time point. This series of serum levels will be completed an average of every 10 weeks across pregnancy, and postpartum.


Secondary Outcome Measures:
  • Infant (umbilical cord)/Maternal ratio of LTG [ Time Frame: 30 min ] [ Designated as safety issue: No ]
    Ratio of umbilical cord (infant) LTG serum level to maternal LTG serum level will be determined at delivery.

  • 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. ] [ Designated as safety issue: No ]
    To determine if there is a pattern of increasing scores on self-report depression assessment (IDS-SR) and declining L/D ratios. Increasing scores indicate worsening symptoms or depression episode recurrence.

  • 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. ] [ Designated as safety issue: No ]
    To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining L/D ratios.

  • 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. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Percent increase in estradiol levels and their correlation to percent decrease in LTG L/D ratio [ Time Frame: Estradiol levels will be examined an average of every 10 weeks from the time the participant enters the study, up to 12 weeks postpartum. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood serum specimen will be obtained to measure lamotrigine 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.


Estimated Enrollment: 10
Study Start Date: September 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Lamotrigine for Bipolar
antepartum and peripartum women taking lamotrigine for Bipolar Disorder
Drug: lamotrigine
Lamotrigine will be observed in women who have already under the guidance of a physician decide to continue lamotrigine for the treatment of Bipolar Disorder
Other Name: Lamictal, Lamiktal, Labileno, Triazines

Detailed Description:

There is an increased risk of recurrence of Bipolar Disorder (BD) episodes or worsening symptoms in pregnancy after the discontinuation of mood stabilizers. Similarly, changes in medication concentration due to the physiological changes in pregnancy may effectively reduce the medication dose and thus its efficacy in pregnancy. Therapeutic dose monitoring has proven to have great utility in preventing seizure recurrence in women with epilepsy (WWE), specifically, dose monitoring of lamotrigine (LTG). Similar guidelines to that of women with epilepsy would benefit pregnant women with BD who are taking lamotrigine (LTG) in pregnancy. However, the pharmacokinetics as well as the utility of therapeutic dose monitoring of LTG in pregnant patients with Bipolar Disorder has not been well studied.

This study is an observational protocol to explore the longitudinal pharmacokinetics (PK) of LTG during pregnancy and postpartum in 10 women with Bipolar Disorder. The correlation between changes in bioavailability and level-to-dose (L/D) ratios and increases in symptoms of depression, mania and anxiety and recurrence of syndromal BD episodes that fulfill Diagnostic and Statistics Manual of Mental Disorders (IV) (DSM4) criteria will be investigated.

The primary aims of this study are 1.) To assess the impact of the dynamic physiology of pregnancy on the L/D ratio and bioavailability of LTG in women with BD. 2.) To evaluate the correlations between maternal and umbilical cord LTG serum levels. 3.) To explore the relationship between declining LTG L/D ratios during pregnancy, bioavailability and the increase in psychiatric symptoms and recurrence of syndromal BD. 4.) To explore the relationship between declining LTG L/D ratios during pregnancy, bioavailability and the recurrence of anxiety symptoms.

Additionally this study will evaluate correlations between estradiol levels and change in LTG L/D ratios during pregnancy. To optimize the research yield from this investigation, participants will have the option to allow banking of cerebrospinal (CSF) fluid and DNA for future analyses.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Participants 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 for Bipolar Disorder, any subtype, will be enrolled into the study.

Criteria

Inclusion Criteria:

  • Age 18 or older
  • If Pregnant, equal to or less than 12 weeks
  • English-speaking
  • DSM-IV Bipolar Disorder, any subtype
  • Able to provide informed consent
  • Once daily dosing of Lamictal

Exclusion Criteria:

  • Active substance abuse within last 6 months and/or positive urine drug screen
  • Active suicidality
  • No obstetrical care
  • Antiepileptic drugs that affect metabolism of LTG
  • Medications in FDA categories F or X that are not antimanic drugs
  • Liver or kidney disease
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01996293

Contacts
Contact: Stephanie A Schuette, BA 312-695-6010 ext 56010 nwu-sas375@northwestern.edu
Contact: Crystal T Clark, MD, MSc 312-695-8648 crystal.clark@northwestern.edu

Locations
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Crystal T Clark, MD, MSc    312-695-8648    crystal.clark@northwestern.edu   
Principal Investigator: Crystal T Clark, MD, MSc         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Crystal T Clark, MD, MSc Assistant Professor
  More Information

Publications:
Responsible Party: Crystal Clark, Assistant Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT01996293     History of Changes
Other Study ID Numbers: 00079810
Study First Received: November 15, 2013
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
pregnant
bipolar
lamotrigine
lamictal
women
female

Additional relevant MeSH terms:
Anticonvulsants
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Lamotrigine
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on August 19, 2014