FMRI Study of Brain Response Before and After Lithium Treatment in People With Bipolar Disorder - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00596622

Purpose

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.

Condition	Intervention	Phase
Bipolar Disorder	Drug: Lithium Behavioral: Picture response during fMRI	Phase IV

MedlinePlus related topics: Bipolar Disorder Depression

Drug Information available for: Lithium carbonate Lithium citrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment
Official Title:	Dysfunctional Cortico-Limbic Activity and Connectivity in Bipolar Disorder Before and After Lithium Treatment: An fMRI Study

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Hamilton Depression Rating Scale (HDRS) [ Time Frame: Measured at Week 10 ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	August 2007
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Healthy participants who undergo functional magnetic resonance imaging (fMRI)	Behavioral: Picture response during fMRI While undergoing an fMRI scan, participants will be presented with pictures, letters, words, and sounds to evoke emotional responses. There will be a maximum of three MRI scans over 9 weeks.
2: Experimental Participants with bipolar disorder who undergo fMRI	Behavioral: Picture response during fMRI While undergoing an fMRI scan, participants will be presented with pictures, letters, words, and sounds to evoke emotional responses. There will be a maximum of three MRI scans over 9 weeks.
3: Experimental Participants with bipolar disorder who undergo fMRI and lithium treatment	Drug: Lithium 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. Behavioral: Picture response during fMRI While undergoing an fMRI scan, participants will be presented with pictures, letters, words, and sounds to evoke emotional responses. There will be a maximum of three MRI scans over 9 weeks.

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 both participants who are healthy and participants 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. Both groups of 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 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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria for BD participants:

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

Inclusion criteria for BD depressed participants:

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

Inclusion criteria for BD (hypo) manic participants:

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

Exclusion criteria for BD participants:

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
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

Exclusion criteria for healthy participants:

Current or past history of psychiatric illness or substance abuse or dependence in self or a first degree relative
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596622

Contacts

Contact: Abigail D. French, MS	317-274-0318	abdfrenc@iupui.edu
Contact: Amit Anand, MD	317-274-7422

Locations

United States, Indiana
Indiana University Psychiatric Clinic	Recruiting
Indianapolis, Indiana, United States, 46222
Contact: Abigail D. French, MS 317-274-0318 abdfrenc@iupui.edu
Principal Investigator: Amit Anand, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Amit Anand, MD

Indiana University School of Medicine

More Information

Click here for more information on this study through Indiana University School of Medicine This link exits the ClinicalTrials.gov site

Responsible Party:	Indiana University School of Medicine, Department of Psychiatry ( Amit Anand, MD )
Study ID Numbers:	R01 MH075025, 0607-23, DATR A3-NSS
Study First Received:	January 8, 2008
Last Updated:	September 25, 2008
ClinicalTrials.gov Identifier:	NCT00596622
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

Major Depressive or Manic Episodes
Bipolar
Mania
Depression

Lithium
fMRI
Pictures
Brain Scan

Study placed in the following topic categories:

Affective Disorders, Psychotic
Depression
Mental Disorders
Bipolar Disorder
Mood Disorders

Lithium Carbonate
Psychotic Disorders
Depressive Disorder
Lithium

Additional relevant MeSH terms:

Disease
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors

Antipsychotic Agents
Antimanic Agents
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Central Nervous System Agents
Antidepressive Agents

ClinicalTrials.gov processed this record on February 10, 2009