Lithium Therapy: Understanding Mothers, Metabolism and Mood

NCT02490241 | Completed DMC

• 1 other identifier: 00200026
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Bipolar Disorder

Keywords

pregnant; female; women; lithium; bipolar

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  30 min

• Scores on Depression assessment, Inventory of Depression Symptomatology- Self Report (IDS-SR)

  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)

  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)

  Participants will complete these assessments an average of every 10 weeks from the time they enter the study, up to 12 weeks postpartum.

Interventions

Lithium DRUG

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.

Also known as: lithium carbonate

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Related Links

• Completed manuscript of pharmacokinetic analysis

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood serum specimen will be obtained to measure lithium levels. Urine will be collected to measure lithium levels and creatinine clearance. Standard of care labs will be obtained on every participant that is eligible and signs informed consent. 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.

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium; Lithium Carbonate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Crystal T Clark, MD, MSc

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: July 3, 2015
• Study Start: April 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: June 1, 2020
• Last Updated: October 5, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)