Bipolar DisorderLiThiUMNCT02490241
Lithium Therapy: Understanding Mothers, Metabolism and Mood
An observational study of Bipolar Disorder, run by Northwestern University at 1 site in United States.
Trial summary
Lithium, the gold standard for treatment of Bipolar Disorder (BD) and a common augmentation to medication therapy for Major Depression, is commonly continued in pregnancy due to its therapeutic benefit and more recent data that suggests the teratogenic effects of lithium are less than historically believed. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lithium
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Jun 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 55 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Pre-conception planning and pregnant women taking lithium 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.
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, Major Depressive Disorder, or Mood Disorder Not Otherwise Specified
- Able to provide informed consent
- Daily dosing of lithium
Who cannot join
- Active substance abuse within last 6 months and/or positive urine drug screen
- Active suicidality
- No obstetrical care
- Use of other drugs that affect metabolism of lithium
- Medications in FDA categories F or X that are not antimanic drugs
- Chronic Kidney Disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Memorial Hospital
Chicago, Illinois, 60611
About this study
Lithium, the gold standard for treatment of Bipolar Disorder (BD) and a common augmentation to medication therapy for Major Depression, is commonly continued in pregnancy due to its therapeutic benefit and more recent data that suggests the teratogenic effects of lithium are less than historically believed. Due to the increased elimination of lithium during pregnancy, lithium concentration decreases in the blood and women with BD are vulnerable to BD episode recurrence in pregnancy. Uncontrolled symptoms of BD in pregnancy increase the risk for postpartum exacerbation of BD and psychosis. Our study will investigate the pharmacokinetics (PK) of lithium prior to pregnancy, during pregnancy, and postpartum. Twenty women taking lithium in pregnancy or planning to become pregnant and continue lithium will be invited to participate in a study to measure repeated blood levels of lithium at six time points between preconception and 3 months postpartum. The data collected will inform the dose, timing of dose, and frequency of dosing of lithium that will lead to fewer untoward effects for the mother and baby. Change in elimination clearance of lithium will be correlated with symptom worsening to develop a dosing algorithm that will help maintain wellness for pregnant women with mood disorders.
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). Similar guidelines to that of women with epilepsy would benefit pregnant women with BD who are taking mood stabilizing medications in pregnancy. Current evidence suggests that lithium has a more favorable reproductive profile than many mood stabilizing antiepileptic agents. However, the pharmacokinetics as well as the utility of therapeutic dose monitoring of lithium in pregnant patients with Bipolar Disorder has not been well studied.
This study is an observational protocol to explore the longitudinal pharmacokinetics (PK) of lithium during pregnancy and postpartum in 20 women with Bipolar Disorder. The correlation between changes in bioavailability and concentrations 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 describe the changes in lithium elimination and serum concentration across pregnancy and postpartum to establish its efficacious use and dosing requirements during childbearing 2.) To evaluate the associations between maternal and umbilical cord lithium serum levels. 3.) To explore the relationship between declining lithium serum concentrations during pregnancy and the increase in psychiatric symptoms and recurrence of syndromal BD.
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
- Lithium
- Keywords
- pregnant, female, women, lithium, bipolar
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called lithium carbonate
Patients taking lithium as a mood stabilizer during pregnancy are eligible to participate in the study. Their dose and serum concentration levels of lithium will be monitored throughout pregnancy and up to three months postpartum.
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, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 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 time 0 and at hours 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.
All urine excreted during participant's overnight research visits will be collected to perform lithium and creatinine clearance tests.
Measured: An average of every 10 weeks, beginning at the preconception visit where a baseline concentration level will be established, at 3 timepoints throughout pregnancy, and at two and twelve weeks postpartum
Secondary outcomes (4)
Infant (umbilical cord)/Maternal ratio of lithium
Ratio of umbilical cord (infant) lithium serum level to maternal lithium 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 posted3 Jul 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2019
- Study completionJun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 9 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, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02490241
- Sponsor's protocol ID
- 00200026
- Acronym
- LiThiUM
- Status last verified
- Oct 2022
- First submitted
- 26 May 2015
- Last updated
- 5 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lithium Therapy: Understanding Mothers, Metabolism and Mood
- ClinicalTrials.gov ID
- NCT02490241
- Acronym / sponsor ID
- LiThiUM / 00200026
- Conditions
- Bipolar Disorder
- Keywords
- pregnant, female, women, lithium, bipolar
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Dec 2019 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 3 Jul 2015 (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.
Lithium, the gold standard for treatment of Bipolar Disorder (BD) and a common augmentation to medication therapy for Major Depression, is commonly continued in pregnancy due to its therapeutic benefit and more recent data that suggests the teratogenic effects of lithium are less than historically believed. Due to the increased elimination of lithium during pregnancy, lithium concentration decreases in the blood and women with BD are vulnerable to BD episode recurrence in pregnancy. Uncontrolled symptoms of BD in pregnancy increase the risk for postpartum exacerbation of BD and psychosis. Our study will investigate the pharmacokinetics (PK) of lithium prior to pregnancy, during pregnancy, and postpartum. Twenty women taking lithium in pregnancy or planning to become pregnant and continue lithium will be invited to participate in a study to measure repeated blood levels of lithium at six time points between preconception and 3 months postpartum. The data collected will inform the dose, timing of dose, and frequency of dosing of lithium that will lead to fewer untoward effects for the mother and baby. Change in elimination clearance of lithium will be correlated with symptom worsening to develop a dosing algorithm that will help maintain wellness for pregnant women with mood disorders.
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). Similar guidelines to that of women with epilepsy would benefit pregnant women with BD who are taking mood stabilizing medications in pregnancy. Current evidence suggests that lithium has a more favorable reproductive profile than many mood stabilizing antiepileptic agents. However, the pharmacokinetics as well as the utility of therapeutic dose monitoring of lithium in pregnant patients with Bipolar Disorder has not been well studied.
This study is an observational protocol to explore the longitudinal pharmacokinetics (PK) of lithium during pregnancy and postpartum in 20 women with Bipolar Disorder. The correlation between changes in bioavailability and concentrations 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 describe the changes in lithium elimination and serum concentration across pregnancy and postpartum to establish its efficacious use and dosing requirements during childbearing 2.) To evaluate the associations between maternal and umbilical cord lithium serum levels. 3.) To explore the relationship between declining lithium serum concentrations during pregnancy and the increase in psychiatric symptoms and recurrence of syndromal BD.
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
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Pre-conception planning and pregnant women taking lithium 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.
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, Major Depressive Disorder, or Mood Disorder Not Otherwise Specified
- 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
- Use of other drugs that affect metabolism of lithium
- 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 |
|---|---|---|
| LithiumAlso: lithium carbonatePatients taking lithium as a mood stabilizer during pregnancy are eligible to participate in the study. Their dose and serum concentration levels of lithium will be monitored throughout pregnancy and up to three months postpartum. | Drug | – |
Primary outcome
Change in Serum concentration/elimination
Time frame: An average of every 10 weeks, beginning at the preconception visit where a baseline concentration level will be established, at 3 timepoints throughout pregnancy, and at two and twelve weeks postpartum
For patients on 1x day dosing, serum levels will be obtained beginning at time 0 and at hours, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 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 time 0 and at hours 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. All urine excreted during participant's overnight research visits will be collected to perform lithium and creatinine clearance tests.
4 secondary outcomes
Infant (umbilical cord)/Maternal ratio of lithium
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 5 Oct 2022.
- Individual participant dataSharing planned: No
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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
Northwestern University
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 5 Oct 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, beginning at the preconception visit where a baseline concentration level will be established, at 3 timepoints throughout pregnancy, and at two and twelve weeks postpartum). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Oct 2022.