Bipolar DisorderPhase 4NCT00596622
FMRI Study of Brain Response Before and After Lithium Treatment in People With Bipolar Disorder
A Phase 4 study testing Lithium in people with Bipolar Disorder, run by Indiana University at 1 site in United States.
Trial summary
This study will assess the effects of bipolar disorder on brain activity and will determine if medication changes the brain activity in people with bipolar disorder. Read more about this study
- Who is it for?
- Ages 15 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Lithium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Nov 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Meets DSM-IV criteria for bipolar I or II disorder
- Meets criteria to undergo an MRI scan based on MRI screening questionnaire
- Suited for outpatient care during the study as ascertained by a score of less than 5 on the Clinical Global Severity Scale, no significant suicidal or homicidal ideation, and no severe disability
- Meets criteria for DSM-IV depressive episode-current
- Score of greater than 15 but less than 30 on the 17-item HDRS
- Score of less than 12 on the Young Mania Rating Scale
Show all 14Show fewer
- Meets criteria for DSM-IV manic episode-current
- Score of less than or equal to 18 on the 17-item HDRS
- Score of greater than 12 but less than 25 on the Young Mania Rating Scale
- Satisfy criteria for DSM-IV for euthymic state-current for at least 2 weeks.
- 17-item Hamilton Depression Rating Scale < 12; Young Mania Rating Scale score < 10
- Ages 18-60 years (inclusive) and able to give voluntary informed consent.
- No current or past history of psychiatric illness or substance abuse or dependence.
- No current or past history of psychiatric illness or substance abuse or dependence in a first degree relative.
Who cannot join
- Meets DSM-IV criteria for unipolar depression, schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, anxiety disorder as a primary diagnosis, mental retardation, or personality disorder
- Received electroconvulsive therapy in the 12 months prior to study entry
- Use of neuroleptics, mood stabilizers, or benzodiazepines in the 2 weeks prior to study entry
- Use of antidepressants in the 2 weeks prior to study entry
- Use of fluoxetine in the 5 weeks prior to study entry
- Use of lithium in the 6 months prior to study entry
Show all 32Show fewer
- Acutely suicidal or homicidal or requiring inpatient treatment
- Meets DSM-IV criteria for substance/alcohol dependence, excluding caffeine or nicotine, in the 6 months prior to study entry or substance/alcohol abuse in the 3 months prior to study entry
- Use of alcohol in the 1 week prior to study entry and refusal to avoid alcohol use during the course of the study
- Presence of serious acute or chronic medical or neurological illness, including previously known HIV positive status (due to possible CNS involvement) as assessed by history, physical examination, and laboratory examination
- Pregnant or breastfeeding
- Metallic implants or other contraindication to MRI
- Inclusion criteria for first degree relatives of bipolar disorder subjects:
- Ages 15-60 years (inclusive) and able to give voluntary informed consent.
- Have never satisfied criteria for DSM-IV BD.
- Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire.
- 17-item Hamilton Depression Rating Scale < 10; Young Mania Rating Scale score < 10
- Exclusion criteria for first degree relatives of bipolar disorder subjects:
- Under 15 years of age.
- Meeting DSM-IV criteria for current episode of unipolar depression
- Pregnant or breast feeding.
- Metallic implants or other contraindication to MRI.
- Currently taking any prescription or centrally acting medications.
- Serious acute or chronic medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry.
- Use of alcohol in the past 1 week and not being able to avoid alcohol use during the course of the study.
- Under 18 years of age
- Pregnant or breastfeeding
- Metallic implants or other contraindication to MRI
- Significant family history of psychiatric or neurological illness
- Currently taking any prescription or centrally acting medications
- Serious acute or chronic medical or neurological illness as assessed by history, physical examination, and laboratory examination
- Use of alcohol in the 1 week prior to study entry and refusal to avoid alcohol use during the course of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Psychiatric Clinic
Indianapolis, Indiana, 46222
About this study
Official title: Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder Before and After Lithium Treatment: An fMRI Study
This study will assess the effects of bipolar disorder on brain activity and will determine if medication changes the brain activity in people with bipolar disorder.
Read the detailed description
Bipolar disorder (BD) is a chronic brain disorder that causes dramatic changes in a person's mood and energy. People with BD undergo periods of extreme happiness and extreme sadness, known as episodes of mania and depression. A person undergoing an episode of mania often experiences euphoric moods, increased energy, and aggressive behaviors, while a person in a depressed state often experiences low moods, lack of energy, and feelings of sadness. Researchers have recently discovered that abnormalities in certain brain areas that control emotion are often present in those with BD. It is believed that the severe mood shifts in BD may cause alterations in normal brain activity, specifically in corticolimbic activation and connectivity. Current mood stabilizing medications used to treat people with BD may help normalize these brain activity abnormalities. This study will assess the effects of BD on brain activity using functional magnetic resonance imaging (fMRI) and will determine if treatment with lithium changes the brain activity in people with BD.
This 9-week study will include participants who are healthy, have BD, or are siblings of subject with BD. All potential participants will undergo initial testing, which will include a physical examination, blood tests, and an electrocardiogram (EKG). Participants will also be asked to answer questions about their mental health, drug use, personality, family history, and psychological well-being. Eligible participants will then return on a different day to undergo an MRI scan, taking 4 hours to complete. During the scan, participants will be asked to perform tasks designed to show changes in blood flow in specific brain regions. These tasks will include listening to sounds and looking at various letters, words, and pictures. This will mark the completion of the study for healthy participants, first degree relatives, and those participants with BD who do not wish to receive medication treatment.
Following the first MRI scan, participants with BD who wish to undergo medication treatment will begin an 8-week course of lithium. Participants will be asked to come to the clinic at least once a week for medication monitoring visits. During these visits, participants will undergo blood draws and assessments on depression and mania. Participants will return for two repeat MRI scans after Weeks 2 and 8 of lithium treatment.
- Conditions
- Bipolar Disorder
- Being tested
- Lithium
- Keywords
- Major Depressive or Manic Episodes, Bipolar, Mania, Depression, Lithium, fMRI, Pictures, Brain Scan
- Medical subject headings
- Bipolar Disorder, Mania, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Dosing will start as one 300-mg capsule per day and will be titrated up to four 300-mg capsules per day for a total of 8 weeks of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Bipolar Manic Subjects Treated | Experimental | Bipolar mania picture response during fMRI before and after treatment with lithium Receives: Drug: Lithium |
| Bipolar Depressed Subjects Treated | Experimental | Bipolar depression picture response during fMRI before and after treatment with lithium Receives: Drug: Lithium |
| Bipolar Euthymic Subjects Treated | Experimental | Bipolar euthymia picture response before and after treatment with lithium Receives: Drug: Lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
17-item Hamilton Depression Rating Scale (HDRS)
17-item HDRS is gold standard for measurement of depression with a range from 0 - 52. 10 - 14: mild depression; 14-20 moderate depression; >20: severe and very severe depression.
Measured: Measured at Baseline and after 8 weeks of treatment
Secondary outcomes (1)
Young Mania Rating Scale
Gold standard scale to measure mania, Range 0 - 60; 12 - 15 mild mania; 15 - 20 moderate mania; >20 severe mania
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2008 (estimated)
- Study startAug 2007
- Primary completionJan 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Indiana 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Amit Anand, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00596622
- Sponsor's protocol ID
- R01MH075025
- Other IDs
- 0607-23, DATR A3-NSS, R01MH075025
- Status last verified
- Aug 2016
- First submitted
- 8 Jan 2008
- Last updated
- 17 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder Before and After Lithium Treatment: An fMRI Study
- ClinicalTrials.gov ID
- NCT00596622
- Acronym / sponsor ID
- R01MH075025
- Conditions
- Bipolar Disorder
- Keywords
- Major Depressive or Manic Episodes, Bipolar, Mania, Depression, Lithium, fMRI, Pictures, Brain Scan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2007
- Primary completion
- Jan 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 17 Jan 2008 (estimated)
- Results
- Posted 17 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the effects of bipolar disorder on brain activity and will determine if medication changes the brain activity in people with bipolar disorder.
Detailed description
Bipolar disorder (BD) is a chronic brain disorder that causes dramatic changes in a person's mood and energy. People with BD undergo periods of extreme happiness and extreme sadness, known as episodes of mania and depression. A person undergoing an episode of mania often experiences euphoric moods, increased energy, and aggressive behaviors, while a person in a depressed state often experiences low moods, lack of energy, and feelings of sadness. Researchers have recently discovered that abnormalities in certain brain areas that control emotion are often present in those with BD. It is believed that the severe mood shifts in BD may cause alterations in normal brain activity, specifically in corticolimbic activation and connectivity. Current mood stabilizing medications used to treat people with BD may help normalize these brain activity abnormalities. This study will assess the effects of BD on brain activity using functional magnetic resonance imaging (fMRI) and will determine if treatment with lithium changes the brain activity in people with BD.
This 9-week study will include participants who are healthy, have BD, or are siblings of subject with BD. All potential participants will undergo initial testing, which will include a physical examination, blood tests, and an electrocardiogram (EKG). Participants will also be asked to answer questions about their mental health, drug use, personality, family history, and psychological well-being. Eligible participants will then return on a different day to undergo an MRI scan, taking 4 hours to complete. During the scan, participants will be asked to perform tasks designed to show changes in blood flow in specific brain regions. These tasks will include listening to sounds and looking at various letters, words, and pictures. This will mark the completion of the study for healthy participants, first degree relatives, and those participants with BD who do not wish to receive medication treatment.
Following the first MRI scan, participants with BD who wish to undergo medication treatment will begin an 8-week course of lithium. Participants will be asked to come to the clinic at least once a week for medication monitoring visits. During these visits, participants will undergo blood draws and assessments on depression and mania. Participants will return for two repeat MRI scans after Weeks 2 and 8 of lithium treatment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bipolar Manic Subjects Treated | Experimental | Drug: LithiumBipolar mania picture response during fMRI before and after treatment with lithium |
| Bipolar Depressed Subjects Treated | Experimental | Drug: LithiumBipolar depression picture response during fMRI before and after treatment with lithium |
| Bipolar Euthymic Subjects Treated | Experimental | Drug: LithiumBipolar euthymia picture response before and after treatment with lithium |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Meets DSM-IV criteria for bipolar I or II disorder
- Meets criteria to undergo an MRI scan based on MRI screening questionnaire
- Suited for outpatient care during the study as ascertained by a score of less than 5 on the Clinical Global Severity Scale, no significant suicidal or homicidal ideation, and no severe disability
- Meets criteria for DSM-IV depressive episode-current
- Score of greater than 15 but less than 30 on the 17-item HDRS
Key exclusion criteria (32 listed)
- Meets DSM-IV criteria for unipolar depression, schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, anxiety disorder as a primary diagnosis, mental retardation, or personality disorder
- Received electroconvulsive therapy in the 12 months prior to study entry
- Use of neuroleptics, mood stabilizers, or benzodiazepines in the 2 weeks prior to study entry
- Use of antidepressants in the 2 weeks prior to study entry
- Use of fluoxetine in the 5 weeks prior to study entry
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 |
|---|---|---|
| LithiumDosing will start as one 300-mg capsule per day and will be titrated up to four 300-mg capsules per day for a total of 8 weeks of treatment. | Drug | Bipolar Depressed Subjects Treated, Bipolar Euthymic Subjects Treated, Bipolar Manic Subjects Treated |
Primary outcome
17-item Hamilton Depression Rating Scale (HDRS)
Time frame: Measured at Baseline and after 8 weeks of treatment
17-item HDRS is gold standard for measurement of depression with a range from 0 - 52. 10 - 14: mild depression; 14-20 moderate depression; >20: severe and very severe depression.
1 secondary outcome
Young Mania Rating Scale
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Amit Anand, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lithium in people with Bipolar Disorder, run by Indiana 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 14 inclusion and 32 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 17 Oct 2016. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
17-item Hamilton Depression Rating Scale (HDRS) (time frame: Measured at Baseline and after 8 weeks of treatment). 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 17 Oct 2016.