Bipolar DisorderNCT03336918
Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder
An observational study of Bipolar Disorder and Bipolar I Depression, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder, Bipolar I Depression, Bipolar II Depression
- What is being tested?
- Lithium
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2017to 30 Jun 2025
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Bipolar disorder and healthy controls
Who may be able to join
- ages 18-60 years (inclusive) and able to give voluntary informed consent;
- Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for BD I or II, current Depressive Episode;
- 17-item Hamilton Depression Rating Scale (HAM-D) score >15 and <25;
- Young Mania Rating Scale (YMRS) < 8;
- no psychotropics in the last 2 weeks (if previously on fluoxetine then medication free for 5 weeks) OR on stable psychotropic medications for 12 weeks
- no lithium treatment for past 6 months;
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- satisfy criteria to undergo an MRI scan based on MRI screening questionnaire;
- able to be managed as outpatients during the study as ascertained by Clinical Global Severity Scale < 5 (i.e., moderately ill) and no significant suicidal or homicidal ideation or gross disability.
- ages 18-60 years and ability to give voluntary informed consent;
- no history of psychiatric illness or substance abuse or dependence;
- no significant family history of psychiatric or neurological illness in first degree relative;
- not currently taking any prescription or centrally acting medications;
- no use of alcohol in the past 1 week;
- and no serious medical or neurological illness.
Who cannot join
- meeting DSM-IV criteria for schizophrenia, schizoaffective disorder, or an anxiety disorder as
- a primary diagnosis;
- requiring inpatient treatment;
- meeting DSM-V criteria for substance dependence within the past 3 months, except caffeine or nicotine;
- positive urinary toxicology screening at screening visit;
- use of alcohol in the past 1 week;
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- serious medical or neurological illness;
- current pregnancy or breast feeding;
- metallic implants or other contraindications to MRI.
- under 18 years of age;
- pregnant or breast-feeding;
- metallic implants or other contraindication to MRI.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Foundation Center for Behavioral Health
Cleveland, Ohio, 44195
About this study
Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.
Read the detailed description
The premise of this proposal is that the clinical efficacy of lithium in bipolar disorder, and its complex effects on multiple brain physiological functions, may be best deciphered using a network properties-metric approach. This approach is critical because it provides insight into the function of brain networks (e.g., resilience to disruption, central hubs), which is likely to be more closely linked to behavioral outcomes. Furthermore, we will conduct an exploratory investigation of the in vivo molecular effects of lithium by measuring peripheral gene expression. To bring these together, we will also explore whether connectome changes serve as mediator between molecular changes (i.e., gene expression) induced by lithium treatment and behavioral changes (e.g., depression, mood stability, suicidality).
- Conditions
- Bipolar Disorder, Bipolar I Depression, Bipolar II Depression, Bipolar Depression, Depression, Major Depressive Episode
- Being tested
- Lithium
- Keywords
- Bipolar Disorder, Bipolar I and II Depression, Lithium, Depression
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called Lithium carbonate or citrate or Lithium extended release
Open-label lithium treatment for Bipolar Disorder Subjects
Healthy Controls only repeat testing - no intervention
| Study group | Role | What they receive |
|---|---|---|
| Bipolar Disorder I or II Depressed | DSM-V Bipolar I or II Depressed treated with lithium Receives: Drug: Lithium | |
| Healthy Controls | Healthy Controls with no psychiatric history |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity (Fc) changes
Investigate effects of lithium monotherapy treatment of BD on changes in Fc through fMRI imaging from baseline after 2, 8, and 26 weeks of treatment and test whether these changes correlate with improvement in state-related symptoms and longer term mood stability. Healthy controls will also be scanned at the same time points but not treated.
Measured: 2, 8, 26 weeks
Structural Connectivity (Sc) changes
Investigate effects of lithium monotherapy treatment of BD depression on changes in the diffusion weighted imaging Sc through fMRI imaging from baseline after 2, 8, and 26 weeks and test whether these changes correlate with depression severity and mood stability. Healthy controls will also be scanned at the same time points but not treated.
Measured: 2, 8, 26 weeks
Secondary outcomes (1)
Changes in peripheral gene expression
An exploratory investigation of whether lithium-related changes in the functional and structural connectome over time represent a link between shifts in peripheral gene expression and improvement in illness-related measures.Lithium therapy will be associated with changes in gene expression pathways such as the mitochondrial-carnitine shuttle pathway, which in turn will be related to changes in the functional and structural connectome.
Measured: 2, 8, 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start7 Dec 2017
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
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 Brigham and Women's HospitalThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Amit Anand, Brigham and Women's Hospital
- Investigators
- Amit Anand, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03336918
- Sponsor's protocol ID
- 17-441
- Status last verified
- Jul 2026
- First submitted
- 5 Oct 2017
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder
- ClinicalTrials.gov ID
- NCT03336918
- Acronym / sponsor ID
- 17-441
- Conditions
- Bipolar Disorder, Bipolar I Depression, Bipolar II Depression, Bipolar Depression, Depression, Major Depressive Episode
- Keywords
- Bipolar Disorder, Bipolar I and II Depression, Lithium, Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 7 Dec 2017 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 8 Nov 2017 (actual)
- 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 is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.
Detailed description
The premise of this proposal is that the clinical efficacy of lithium in bipolar disorder, and its complex effects on multiple brain physiological functions, may be best deciphered using a network properties-metric approach. This approach is critical because it provides insight into the function of brain networks (e.g., resilience to disruption, central hubs), which is likely to be more closely linked to behavioral outcomes. Furthermore, we will conduct an exploratory investigation of the in vivo molecular effects of lithium by measuring peripheral gene expression. To bring these together, we will also explore whether connectome changes serve as mediator between molecular changes (i.e., gene expression) induced by lithium treatment and behavioral changes (e.g., depression, mood stability, suicidality).
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bipolar Disorder I or II Depressed | – | Drug: LithiumDSM-V Bipolar I or II Depressed treated with lithium |
| Healthy Controls | – | –Healthy Controls with no psychiatric history |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Bipolar disorder and healthy controls
Key inclusion criteria (14 listed)
- ages 18-60 years (inclusive) and able to give voluntary informed consent;
- Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for BD I or II, current Depressive Episode;
- 17-item Hamilton Depression Rating Scale (HAM-D) score >15 and <25;
- Young Mania Rating Scale (YMRS) < 8;
- no psychotropics in the last 2 weeks (if previously on fluoxetine then medication free for 5 weeks) OR on stable psychotropic medications for 12 weeks
Key exclusion criteria (12 listed)
- meeting DSM-IV criteria for schizophrenia, schizoaffective disorder, or an anxiety disorder as
- a primary diagnosis;
- requiring inpatient treatment;
- meeting DSM-V criteria for substance dependence within the past 3 months, except caffeine or nicotine;
- positive urinary toxicology screening at screening visit;
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 carbonate or citrate or Lithium extended releaseOpen-label lithium treatment for Bipolar Disorder Subjects Healthy Controls only repeat testing - no intervention | Drug | Bipolar Disorder I or II Depressed |
Primary outcome
Functional Connectivity (Fc) changes
Time frame: 2, 8, 26 weeks
Investigate effects of lithium monotherapy treatment of BD on changes in Fc through fMRI imaging from baseline after 2, 8, and 26 weeks of treatment and test whether these changes correlate with improvement in state-related symptoms and longer term mood stability. Healthy controls will also be scanned at the same time points but not treated.
Structural Connectivity (Sc) changes
Time frame: 2, 8, 26 weeks
Investigate effects of lithium monotherapy treatment of BD depression on changes in the diffusion weighted imaging Sc through fMRI imaging from baseline after 2, 8, and 26 weeks and test whether these changes correlate with depression severity and mood stability. Healthy controls will also be scanned at the same time points but not treated.
1 secondary outcome
Changes in peripheral gene expression
Time frame: 2, 8, 26 weeks
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 16 Jul 2026.
- 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.
Amit Anand, MD principal investigator
The Cleveland Clinic
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 and Bipolar I Depression, run by Brigham and Women's Hospital 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 14 inclusion and 12 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 16 Jul 2026. 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?
Functional Connectivity (Fc) changes (time frame: 2, 8, 26 weeks). The study lists 2 primary outcomes in all. 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 16 Jul 2026.