The Bipolar Lithium Imaging Scan Study. (BLISS)

The Bipolar Lithium Imaging Scan Study: Imaging Lithium in the Brains of Subjects with Bipolar Disorder

The main goal of this study is to determine if brain lithium-concentrations predict clinical lithium treatment-response. Secondary, to study correlations between intracerebral distribution-patterns of lithium with clinical treatment outcome.

Brain lithium concentrations will be measured using ultra-high field (7 Tesla) lithium magnetic resonance (MR) imaging, which has recently been introduced. Determining lithium-concentrations in the brain has been difficult so far due to lithium's relatively low concentration (compared to protons, which are targeted in conventional MRI). 7T lithium MR imaging has the potential to produce much more detailed MR images compared with previous studies, for the first time. The BLISS study is expected to yield new insights, helping to better understand why clinical lithium response varies between individuals.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder I or II
• Intervention / Treatment: Other: Lithium MR imaging

Detailed Description

Introduction Lithium treatment is considered the first-line pharmacological treatment for bipolar disorder. However, individual responses vary greatly, which undermines the ability to achieve rapid stabilization in many patients with bipolar disorder. The neurobiological mechanisms underlying lithium's action are still largely unknown, which hampers the development of clinically applicable predictors for individual treatment response. The recent introduction of ultra-high-field lithium magnetic resonance imaging offers a promising avenue to better link brain measures with clinical responses to lithium treatment.

Methods and Analysis This is a longitudinal observational study involving 80 adults with bipolar disorder who are initiating lithium as part of their regular treatment regimen. Ultra-high-field lithium magnetic resonance imaging of the brain will be performed within four weeks of reaching stable therapeutic serum lithium concentrations. The primary outcome is clinical response to lithium treatment at one-year follow-up, as measured using a validated questionnaire. Linear regression analysis will be used to establish correlations between brain lithium concentrations-including whole brain, voxel-wise, parcellation, mean, and region-of-interest approaches-and clinical lithium response.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: E Boere; Phone Number: +31(0)715263785; Email: bliss@lumc.nl
• Study Contact Backup: Name: Onderzoekscentrum Psychiatrie, OZC; Email: bliss@lumc.nl

Study Locations

• Netherlands
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2333 ZA
      • Recruiting
      • Leiden University Medical Center
      • Contact: E Boere, MD; Phone Number: +31715263785; Email: bliss@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with bipolar disorder type I or II who start with lithium treatment as part of standard care.

Description

Inclusion Criteria:

1. age 18 years or above,
2. a clinical diagnosis of bipolar disorder type I or type II ,
3. having reached stable therapeutic serum lithium concentrations (reference values 0.6-1.0 mM in age to 65 years; 0.4-0.8 in age 65 years and above) within four weeks prior to study participation, and
4. provided written informed consent.

Exclusion Criteria:

1. insufficient comprehension of the Dutch language,
2. unable to provide informed consent,
3. drug or alcohol abuse over a period of two weeks prior to study participation, and
4. meeting any exclusion criterium for MR imaging.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

BLISS candidates; Adult patients with bipolar disorder (BD) type I or II, who have recently started lithium treatment as part of standard care, will be included. At 12-month follow-up, the longitudinal outcome of lithium treatment will be assessed using a validated questionnaire. Based on previous studies, approximately one-third of participants are expected to be classified as full responders at the 12-month follow-up, with another one-third classified as clinical non-responders to lithium treatment.

Other: Lithium MR imaging; After obtaining written informed consent and within four weeks of reaching a stable therapeutic serum lithium concentration, lithium MR imaging will be performed using a 7 Tesla MR system (Achieva, Philips Medical Systems, Eindhoven, The Netherlands) with a dual-tuned 7Li/1H volume head coil (RAPID Biomedical GmbH, Rimpar, Germany). Various approaches, including whole-brain, voxel-wise, parcellation, mean, and regions of interest, will be applied to measure lithium concentrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical lithium response	Clinical lithium response will be assessed using a validated questionnaire.	At 12-month follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum lithium concentrations	Serum lithium concentrations will be determined to establish correlations with brain lithium concentrations.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Manic and depressive symptom severity	Manic and depressive symptom rating scales will be used to assess mood state at the day of scan acquisition.	Baseline

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: PsyQ; GGZ Rivierduinen
• Investigators: Study Chair: E Boere, MD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: bipolar disorder; lithium; clinical; clinical response; 7 Tesla; lithium MR imaging; ultra-high field imaging
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: NL80214.058.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Lithium MR imaging data.
• IPD Sharing Time Frame: Study protocol - currently submitted for OA publication CSR - after termination of the BLISS study Analytic code - after termination of the BLISS study IPD - after termination of the BLISS study

IPD Sharing Access Criteria

Study protocol - open access CSR and analytic code - open access

IPD: lithium imaging data will be made available upon request with the study chair, and no sooner then after study termination.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No