Bipolar DisorderPK-LAPBNCT01996293
Pregnant Women Taking Lamictal for Bipolar Disorder
An observational study of Bipolar Disorder, run by Northwestern University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- lamotrigine
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
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.
Who may be able to join
- Age 18 or older
- If Pregnant, equal to or less than 26 weeks
- English-speaking
- DSM-IV Bipolar Disorder, any subtype
- Able to provide informed consent
- Daily dosing of Lamictal
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Memorial Hospital
Chicago, Illinois, 60611
About this study
Official title: Pharmacokinetics of Lamotrigine in Pregnant and Postpartum Women With Bipolar Disorder
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.
Read the 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.
- Conditions
- Bipolar Disorder
- Being tested
- lamotrigine
- Keywords
- pregnant, bipolar, lamotrigine, lamictal, women, female
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lamotrigineDrug
Also called Lamictal, Lamiktal, Labileno, Triazines
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
| Study group | Role | What they receive |
|---|---|---|
| Lamotrigine for Bipolar | antepartum and peripartum women taking lamotrigine for Bipolar Disorder Receives: Drug: lamotrigine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum concentration/elimination
For patients on 1x day dosing, 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. For patients on 2x dosing, serum levels will be obtained at hours 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16 hours.
Measured: An average of every 10 weeks; Hours 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 16, 20, 24, or 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16
Secondary outcomes (4)
Infant (umbilical cord)/Maternal ratio of LTG
Ratio of umbilical cord (infant) LTG serum level to maternal LTG serum level will be determined at delivery.
Measured: 30 min
Scores on depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR)
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.
Measured: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Scores on mania assessment, Young Mania Reporting Scale (YMRS)
To determine if there is a pattern of increasing scores on clinician administered mania assessment (YMRS) and declining L/D ratios.
Measured: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Scores on anxiety scale, Generalized Anxiety Disorder (GAD-7)
Measured: Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2013 (estimated)
- Study startSep 2013
- Primary completionAug 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Crystal Clark, Northwestern University
- Investigators
- Crystal T Clark, MD, MSc, Principal investigator, Associate Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01996293
- Sponsor's protocol ID
- 00079810
- Acronym
- PK-LAPB
- Status last verified
- Sep 2022
- First submitted
- 15 Nov 2013
- Last updated
- 28 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Nov;170(11):1240-7. doi: 10.1176/appi.ajp.2013.13010006.
PubMed 24185239
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Lamotrigine in Pregnant and Postpartum Women With Bipolar Disorder
- ClinicalTrials.gov ID
- NCT01996293
- Acronym / sponsor ID
- PK-LAPB / 00079810
- Conditions
- Bipolar Disorder
- Keywords
- pregnant, bipolar, lamotrigine, lamictal, women, female
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Aug 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 27 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lamotrigine for Bipolar | – | Drug: lamotrigineantepartum and peripartum women taking lamotrigine for Bipolar Disorder |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (6 listed)
- Age 18 or older
- If Pregnant, equal to or less than 26 weeks
- English-speaking
- DSM-IV Bipolar Disorder, any subtype
- Able to provide informed consent
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lamotrigineAlso: Lamictal, Lamiktal, Labileno, TriazinesLamotrigine will be observed in women who have already under the guidance of a physician decide to continue lamotrigine for the treatment of Bipolar Disorder | Drug | Lamotrigine for Bipolar |
Primary outcome
Change in Serum concentration/elimination
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, or 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16
For patients on 1x day dosing, 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. For patients on 2x dosing, serum levels will be obtained at hours 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16 hours.
4 secondary outcomes
Infant (umbilical cord)/Maternal ratio of LTG
Time frame: 30 min
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Background: PubMed 24185239Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Nov;170(11):1240-7. doi: 10.1176/appi.ajp.2013.13010006.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Crystal T Clark, MD, MSc principal investigator
Associate Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bipolar Disorder, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Serum concentration/elimination (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, or 0, 1, 2, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 13.5, 14.5, and 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01996293, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.