Multimodal Neuroimaging of Treatment Effects in Adolescent Mania

NCT00893581 | Completed DMC

• 1 other identifier: DelBello MM NeuroImaging Study
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mania; Bipolar Disorder

Keywords

mania; adolescent; bipolar

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks

Study Arms (3)

1--Quetiapine & Placebo

ACTIVE COMPARATOR

Quetiapine \& Placebo in the place of Lithium

Drug: Quetiapine & Placebo

2-- Lithium & Placebo

ACTIVE COMPARATOR

Lithium \& Placebo in the place of Quetiapine

Drug: Lithium and Placebo

Placebo

PLACEBO COMPARATOR

Sugar Pill (Placebo) given to mimic drug

Other: Healthy Controls

Interventions

Quetiapine & Placebo DRUG

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.

1--Quetiapine & Placebo

Lithium and Placebo DRUG

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.

2-- Lithium & Placebo

Healthy Controls OTHER

Healthy control (patients given placebo -- sugar pill intended to mimic drug)

Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• University of Cincinnati: lead
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Related Publications (3)

• Lei D, Li W, Qin K, Ai Y, Tallman MJ, Patino LR, Welge JA, Blom TJ, Klein CC, Fleck DE, Gong Q, Adler CM, Strawn JR, Sweeney JA, DelBello MP. Effects of short-term quetiapine and lithium therapy for acute manic or mixed episodes on the limbic system and emotion regulation circuitry in youth with bipolar disorder. Neuropsychopharmacology. 2023 Mar;48(4):615-622. doi: 10.1038/s41386-022-01463-6. Epub 2022 Oct 13.

  PMID: 36229596 DERIVED

• Li W, Lei D, Tallman MJ, Ai Y, Welge JA, Blom TJ, Fleck DE, Klein CC, Patino LR, Strawn JR, Gong Q, Strakowski SM, Sweeney JA, Adler CM, DelBello MP. Pretreatment Alterations and Acute Medication Treatment Effects on Brain Task-Related Functional Connectivity in Youth With Bipolar Disorder: A Neuroimaging Randomized Clinical Trial. J Am Acad Child Adolesc Psychiatry. 2022 Aug;61(8):1023-1033. doi: 10.1016/j.jaac.2021.12.015. Epub 2022 Jan 25.

  PMID: 35091050 DERIVED

• Patino LR, Klein CC, Strawn JR, Blom TJ, Tallman MJ, Adler CM, Welge JA, DelBello MP. A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder. J Child Adolesc Psychopharmacol. 2021 Sep;31(7):485-493. doi: 10.1089/cap.2021.0039. Epub 2021 Sep 14.

  PMID: 34520250 DERIVED

MeSH Terms

Conditions

Mania; Bipolar Disorder

Interventions

Quetiapine Fumarate; Lithium

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Melissa DelBello, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 4, 2009
• First Posted: May 6, 2009
• Study Start: March 1, 2009
• Primary Completion: February 1, 2016
• Study Completion: March 1, 2016
• Last Updated: May 19, 2016

Record last verified: 2015-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)