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

May 4, 2009
June 19, 2014
March 2009
March 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00893581 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Multimodal Neuroimaging of Treatment Effects in Adolescent Mania
Multimodal Neuroimaging of Treatment Effects in Adolescent Mania

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.

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
  • Mania
  • Bipolar Disorder
  • 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
  • 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
  • Other: Healthy Controls
    Healthy control (patients given placebo -- sugar pill intended to mimic drug)
    Other Name: Healthy Controls
  • Active Comparator: 1--Quetiapine & Placebo
    Quetiapine & Placebo in the place of Lithium
    Intervention: Drug: Quetiapine & Placebo
  • Active Comparator: 2--Placebo & Lithium
    Placebo in the place of Quetiapine & Lithium
    Intervention: Drug: Lithium and Placebo
  • Placebo Comparator: Placebo
    Sugar Pill (Placebo) given to mimic drug
    Intervention: Other: Healthy Controls
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
March 2015
March 2015   (final data collection date for primary outcome measure)

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.
Both
12 Years to 17 Years
Yes
Contact: Christy Klein (513) 558-5746 kleinci@ucmail.uc.edu
United States
 
NCT00893581
DelBello MM NeuroImaging Study
Yes
Melissa Delbello, University of Cincinnati
University of Cincinnati
Children's Hospital Medical Center, Cincinnati
Principal Investigator: Melissa DelBello, MD University of Cincinnati
University of Cincinnati
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP