PET and MRI Brain Imaging of Bipolar Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Stony Brook University
Sponsor:
Collaborators:
The Dana Foundation
Information provided by (Responsible Party):
Stony Brook University
ClinicalTrials.gov Identifier:
NCT01880957
First received: June 17, 2013
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

The primary aims of this study are to:

  1. Quantify serotonin transporter (5-HTT) binding potential (BP) in vivo in bipolar disorder patients (BPD) during a major depressive episode (MDE).
  2. Assess the effect of lithium treatment of bipolar disorder on 5-HTT.
  3. Assess the effect of lithium treatment of bipolar disorder on 5-HT1A BP.
  4. Assess the effect of lamotrigine treatment of bipolar disorder on 5-HTT and 5-HT1A BP.

Condition Intervention
Bipolar Disorder
Bipolar Depression
Drug: Lithium
Drug: Lamotrigine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Pathophysiology and Treatment of Bipolar Disorder as Assessed by in Vivo Imaging

Resource links provided by NLM:


Further study details as provided by Stony Brook University:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Patients will have a Hamilton Depression Rating Scale (HDRS) score obtained at baseline; participants must have an HDRS score of at least 15 to be eligible. After 6 weeks of medication treatment, the HDRS score will be reevaluated. Participants who have a 50% or greater decrease in their HDRS score will be considered responders and will proceed to the repeat PET scans.


Estimated Enrollment: 76
Study Start Date: August 2012
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Lithium
Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode
Drug: Lithium
Other Name: lithium carbonate
Lamotrigine
Patients who have not respond to adequate prior lithium treatment while depressed, or who refuse lithium, will be given lamotrigine. Lamotrigine will be started at 25 mg bid and increased to 50 mg bid after 2 weeks and again increased to 100 mg bid after an additional 2 weeks.
Drug: Lamotrigine
Other Name: Lamictal

Detailed Description:

PET and MRI imaging will be used to investigate the aims described above in patients who have bipolar disorder and are currently experiencing a depressive episode. Both healthy controls and depressed participants with bipolar disorder will be recruited. Patients who are on medication before enrolling in the study will have a three week washout. At baseline, healthy controls and patients will have an MRI consisting of both structural and functional sequences. Psychological measures will also be obtained at baseline. Within one week of the MRI, both patients and healthy controls will have one CUMI and one DASB PET scan.

Following the baseline PET scans, patient participants will begin medication treatment with either lithium or lamotrigine, based on the clinical judgement of the treating psychiatrist. Psychological measures will be obtained every 2 weeks. After 6 weeks of medication treatment at a therapeutic dose, patients will be assessed for remission (defined as a 50% decrease in the HDRS score from baseline). If this criteria is met, patient participants will then have follow-up PET scans (one CUMI and one DASB). If this criteria is not met, the patient will be switched to the other medication under study and will be reevaluated after an additional 4 weeks of medication treatment. Patients who still do not demonstrate a 50% decrease in their HDRS will be considered non-responders and will have repeat CUMI and DASB scans.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

PATIENTS

Inclusion Criteria:

  • Bipolar patients suffering from a major depressive episode currently or recently (in the month prior to scanning). Patients on psychiatric medication will have failed their current regimen for the treatment of their depression: they will meet criteria for depression, be seeking treatment for it, and have been on an adequate dose of antidepressant or mood stabilizer (as defined by the Antidepressant Treatment Form—see Oquendo et al., 2003) for 4 weeks or more.
  • Of sufficient severity to score at least 15 on the first 17 items of the Hamilton Depression Rating Scale.
  • Age range 18-65 years.
  • Off all psychotropic and other types of drugs likely to interact with serotonin transporters and 5-HT1A receptors for at least 21 days. Allowed short-acting benzodiazepines for distressing anxiety or insomnia (up to 24 hours prior to each PET scan). Patients will be off neuroleptics for 3 weeks and off fluoxetine for 6 weeks prior to study. Off serotonin depleting drugs such as reserpine for 3 months. Patient will also be off anti-coagulant/anti-platelet treatment such as coumadin, with the exception of aspirin for 10 days.
  • Willing to travel for PET scanning

Exclusion Criteria:

  • Other major psychiatric disorders such as schizophrenia, schizoaffective illness; current drug or alcohol abuse (within past 2 months), or drug or alcohol dependence <6mos ago; anorexia nervosa or bulimia nervosa in the past year; IV drug use or ecstasy use more than two times.
  • A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).
  • Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss and the lab parameters platelet count < 80,000.
  • Lacks capacity to consent.
  • Actively suicidal-begins expressing a plan for suicide during the washout phase or develop suicidal ideation that warrants admission or requires medication or treatment intervention.
  • Electroconvulsive therapy (ECT) within the past 6 months.
  • Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
  • Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel
  • Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.
  • A neurological disease or loss of consciousness for more than a few minutes
  • Medicinal Patch (participants will be asked to remove before MRI)
  • Patients who are responding satisfactorily to psychiatric medications, because they will not be washed-out for purposes of this study
  • A documented history of a lack of response to a trial of adequate dose and duration of both lithium and lamotrigine defined as minimal clinical response to lamotrigine 200 mgs for at least 4 weeks or lithium serum levels of at least 0.8 (or dose >= 900 mgs) for at least 4 weeks.
  • Patient is unlikely to be able to tolerate medication washout
  • Claustrophobia

HEALTHY CONTROLS

Inclusion:

  • No lifetime history of Axis I disorders
  • Age range 18-65 years.
  • Willing to travel for PET scanning.

Exclusion:

  • Past or present alcohol/substance abuse or dependence; IV drug use or ecstasy use more than two times.
  • A first-degree relative with history of major depression, schizophrenia, schizoaffective disorder, or suicide attempt; two or more first degree relatives with a history of substance dependence.
  • Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss, and the following lab parameters: platelet count < 80,000
  • Lacks capacity to consent
  • Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months
  • Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel
  • Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.
  • A neurological disease or loss of consciousness for more than a few minutes
  • Medicinal Patch (participants will be asked to remove before MRI)
  • Subjects on drugs or medication that affect the serotonin system
  • Claustrophobia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01880957

Contacts
Contact: Sunia Choudhury, MA 631 638 1544 Sunia.Choudhury@stonybrookmedicine.edu

Locations
United States, New York
Stony Brook University Recruiting
Stony Brook, New York, United States, 11794
Principal Investigator: Ramin Parsey, MD, PhD         
Sponsors and Collaborators
Stony Brook University
The Dana Foundation
Investigators
Principal Investigator: Ramin Parsey, MD, PhD Stony Brook University
  More Information

No publications provided

Responsible Party: Stony Brook University
ClinicalTrials.gov Identifier: NCT01880957     History of Changes
Other Study ID Numbers: 2012-1826-F, 7R01MH090276-03
Study First Received: June 17, 2013
Last Updated: April 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Stony Brook University:
bipolar disorder
bipolar depression
serotonin transporter
serotonin receptors
binding potential
brain imaging

Additional relevant MeSH terms:
Bipolar Disorder
Depression
Depressive Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Lithium
Lithium Carbonate
Lamotrigine
Anticonvulsants
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on August 20, 2014