Multimodal Neuroimaging of Treatment Effects in Adolescent Mania

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Cincinnati
Sponsor:
Collaborator:
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
Melissa Delbello, University of Cincinnati
ClinicalTrials.gov Identifier:
NCT00893581
First received: May 4, 2009
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

Specific Aim 1: To determine the effects of treatment with quetiapine or lithium on brain activation in adolescents. The investigators will use functional magnetic resonance imaging (fMRI) to examine brain activation during an attentional task.

Specific Aim 2: To determine the effects of treatment with quetiapine or lithium on neurometabolite measures, early in their illness course. The investigators will use 1H-MRS to identify myo-inositol (mI), N-acetyl aspartate (NAA), and glutamate (Glu) levels in prefrontal ALN regions.

Specific Aim 3: To determine the relationships among the changes in brain activation and neurometabolite measures, as well as symptomatic improvement in manic adolescents.


Condition Intervention
Mania
Bipolar Disorder
Drug: Quetiapine & Placebo
Drug: Lithium and Placebo
Other: Healthy Controls

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
Official Title: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • The purpose of this study is to use magnetic resonance imaging (MRI) to examine brain structure, function and chemistry in people with Bipolar I disorder (manic or mixed episodes) who are being treated with either quetiapine or lithium. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: March 2009
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1--Quetiapine & Placebo
Quetiapine & Placebo in the place of Lithium
Drug: Quetiapine & Placebo
Bipolar adolescents will be initiated on 100 mg per day of quetiapine (or placebo) and 30 mg/kg (maximum starting dose of 600 mg twice daily) of lithium carbonate (or placebo), depending on randomization assignment. Patients will be given placebo for the medication to which they were not assigned. Quetiapine will be adjusted based on tolerability and response to a target dose of 400-600 mg and lithium will be adjusted to a target dose based on achieving a serum level of 1.0-1.2 mEq/L.
Other Name: Quetiapine & Placebo
Active Comparator: 2--Placebo & Lithium
Placebo in the place of Quetiapine & Lithium
Drug: Lithium and Placebo
Bipolar adolescents will be initiated on 100 mg per day of quetiapine (or placebo) and 30 mg/kg (maximum starting dose of 600 mg twice daily) of lithium carbonate (or placebo), depending on randomization assignment. Patients will be given placebo for the medication to which they were not assigned. Quetiapine will be adjusted based on tolerability and response to a target dose of 400-600 mg and lithium will be adjusted to a target dose based on achieving a serum level of 1.0-1.2 mEq/L.
Other Name: Lithium and Placebo
Placebo Comparator: Placebo
Sugar Pill (Placebo) given to mimic drug
Other: Healthy Controls
Healthy control (patients given placebo -- sugar pill intended to mimic drug)
Other Name: Healthy Controls

Detailed Description:

Hypotheses 1 & 2 predict that following 6 weeks of treatment with lithium or quetiapine, manic adolescents who demonstrate symptomatic improvement will exhibit normalized (decreased) VLPFC and ACC activation and increased activation of compensatory posterior attentional brain areas as well as normalization of VLPFC and ACC neurometabolite measures (increased NAA and decreased Glu levels) compared with those who do not experience symptomatic improvement and healthy adolescents.

Hypothesis 3 predicts significant associations between fMRI activation changes (i.e. decreased activation in VLPFC and ACC ROIs and increased activation in the posterior attention ROI) and MRS changes (increases in NAA and decreases in Glu levels in the VLPFC and ACC) for patients who exhibit symptomatic improvement with either treatment.

Hypothesis 4 predicts that decreases in mI levels at 1 week will be associated with lithium, but not quetiapine, response at endpoint.

In contrast, Hypothesis 5 predicts higher baseline Cho levels will be associated with quetiapine, but not lithium, response at endpoint.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion/Exclusion Criteria

Inclusion - Bipolar Disorder Subjects:

  • DSM-IV-TR12 criteria for bipolar disorder, type I, manic or mixed episode, diagnosed by the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS)166,101,102-103,104-105,108
  • Baseline YMRS112-114 score > 20;
  • Ages 12-17 years 11 months old;
  • Fluent in English;
  • Provision of written informed consent by a legal guardian and written assent by the subject;
  • Tanner scale stages III-V167, in order to include only post-pubescent subjects and minimize brain changes associated with the onset of puberty;168-169
  • Less than 2 years from onset of bipolar disorder, defined by age at onset of first DSM-IV-TR affective episode (mania, hypomania, depression or mixed), to establish that our sample is early in their illness course;
  • No prior psychiatric hospitalizations, <3 months of lifetime psychotropic medication exposure (with the exception of psychostimulants, since excluding patients with psychostimulant exposure would significantly limit the generalizability of our findings), and no active psychotropic medication during the week (72 hours for psychostimulants and benzodiazepines) prior to the index assessment (no treatment with fluoxetine during the prior month). Please note that patients will NOT be taken off medications for the purpose of this study; instead, this criterion is to exclude subjects receiving treatment at the time of index assessment;
  • Does not have a history of intolerance or non-response to lithium or quetiapine;
  • Manic or depressive symptoms do not result entirely from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by medical evaluation and rapid symptom resolution;
  • No lifetime DSM-IV-TR diagnosis of post-traumatic stress disorder (PTSD), since PTSD has been associated with abnormalities in prefrontal NAA and function170-171,172. Furthermore, bipolar patients with co-occurring PTSD are less likely to respond to lithium monotherapy, and often need a serotonin specific reuptake inhibitor (SSRI) as adjunctive treatment to a mood stabilizer.173,174 ;
  • If female and of child bearing potential, agrees to use one of the following method of birth control: complete abstinence from sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive.

Inclusion - Healthy Controls:

  • Ages of 12-17 years and 11 month;
  • No history of any DSM-IV-TR Axis I disorder (nicotine dependence is permitted);
  • No first- or second-degree relatives with an affective or psychotic disorder;
  • No medications with central nervous system effects within 5 half-lives;
  • Fluent in English;
  • Tanner stage III-V;
  • Provision of informed consent and assent.

Exclusion - Bipolar Subjects & Healthy Controls:

  • Contraindication to an MRI scan (e.g., braces or claustrophobia);
  • An unstable medical or neurological illness that could influence fMRI or MRS results;
  • IQ < 70, as determined by The Wechsler Abbreviated Scale of Intelligence (WASI) ;
  • A positive pregnancy test;
  • A history of major medical or neurological illness or a significant episode (> 10 minutes) of loss of consciousness;
  • Any lifetime DSM-IV-TR substance use disorder (nicotine dependence is permitted);
  • A lifetime DSM-IV-TR diagnosis of any pervasive developmental disorder;
  • The patient lives >100 miles from the University of Cincinnati or is not able to attend follow-up visits.
  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: NCT00893581

Contacts
Contact: Christy Klein (513) 558-5746 kleinci@ucmail.uc.edu

Locations
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Christy Klein    513-558-5746    christina.klein@uc.edu   
Principal Investigator: Melissa DelBello, MD         
Sponsors and Collaborators
University of Cincinnati
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Melissa DelBello, MD University of Cincinnati
  More Information

No publications provided

Responsible Party: Melissa Delbello, Professor, University of Cincinnati
ClinicalTrials.gov Identifier: NCT00893581     History of Changes
Other Study ID Numbers: DelBello MM NeuroImaging Study
Study First Received: May 4, 2009
Last Updated: June 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Cincinnati:
mania
adolescent
bipolar

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Quetiapine
Lithium
Lithium Carbonate
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

ClinicalTrials.gov processed this record on September 22, 2014