Multimodal Neuroimaging of Treatment Effects in Adolescent Mania

May 18, 2016 updated by: Melissa Delbello, University of Cincinnati

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

169

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
ACTIVE_COMPARATOR: 2-- Lithium & Placebo
Lithium & Placebo in the place of Quetiapine
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.
PLACEBO_COMPARATOR: Placebo
Sugar Pill (Placebo) given to mimic drug
Other: Healthy Controls
Healthy control (patients given placebo -- sugar pill intended to mimic drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cincinnati

Collaborators

Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (ACTUAL)

February 1, 2016

Study Completion (ACTUAL)

March 1, 2016

Study Registration Dates

First Submitted

May 4, 2009

First Submitted That Met QC Criteria

May 5, 2009

First Posted (ESTIMATE)

May 6, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

May 19, 2016

Last Update Submitted That Met QC Criteria

May 18, 2016

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DelBello MM NeuroImaging Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bipolar Disorder

Clinical Trials on Quetiapine & Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Russia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe