ManiaNCT00893581
Multimodal Neuroimaging of Treatment Effects in Adolescent Mania
A study of Mania and Bipolar Disorder, run by University of Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Mania, Bipolar Disorder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 169 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to Mar 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Show all 19Show fewer
- 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;
- No medications with central nervous system effects within 5 half-lives;
- Fluent in English;
- Tanner stage III-V;
- Provision of informed consent and assent.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Mania, Bipolar Disorder
- Being tested
- Quetiapine & Placebo, Lithium and Placebo, Healthy Controls
- Keywords
- mania, adolescent, bipolar
- Medical subject headings
- Mania, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quetiapine & PlaceboDrug
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.
Lithium and PlaceboDrug
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.
Healthy ControlsOther
Healthy control (patients given placebo -- sugar pill intended to mimic drug)
| Study group | Role | What they receive |
|---|---|---|
| 1--Quetiapine & Placebo | Active comparator | Quetiapine \& Placebo in the place of Lithium Receives: Drug: Quetiapine & Placebo |
| 2-- Lithium & Placebo | Active comparator | Lithium \& Placebo in the place of Quetiapine Receives: Drug: Lithium and Placebo |
| Placebo | Placebo comparator | Sugar Pill (Placebo) given to mimic drug Receives: Other: Healthy Controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startMar 2009
- Primary completionFeb 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ManiaStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Responsible party
- Principal investigator, Melissa Delbello, University of Cincinnati
- Investigators
- Melissa DelBello, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00893581
- Sponsor's protocol ID
- DelBello MM NeuroImaging Study
- Status last verified
- May 2015
- First submitted
- 4 May 2009
- Last updated
- 19 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 36229596Li 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.
PubMed 35091050Patino 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.
PubMed 34520250
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Neuroimaging of Treatment Effects in Adolescent Mania
- ClinicalTrials.gov ID
- NCT00893581
- Acronym / sponsor ID
- DelBello MM NeuroImaging Study
- Conditions
- Mania, Bipolar Disorder
- Keywords
- mania, adolescent, bipolar
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati
- Study start
- Mar 2009
- Primary completion
- Feb 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 6 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1--Quetiapine & Placebo | Active comparator | Drug: Quetiapine & PlaceboQuetiapine \& Placebo in the place of Lithium |
| 2-- Lithium & Placebo | Active comparator | Drug: Lithium and PlaceboLithium \& Placebo in the place of Quetiapine |
| Placebo | Placebo comparator | Other: Healthy ControlsSugar Pill (Placebo) given to mimic drug |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- 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;
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quetiapine & PlaceboBipolar 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. | Drug | 1--Quetiapine & Placebo |
| Lithium and PlaceboBipolar 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. | Drug | 2-- Lithium & Placebo |
| Healthy ControlsHealthy control (patients given placebo -- sugar pill intended to mimic drug) | Other | Placebo |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2016.
- Derived from this study: PubMed 36229596Lei 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.
- Derived from this study: PubMed 35091050Li 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.
- Derived from this study: PubMed 34520250Patino 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.
- Individual participant dataSharing planned: No
Related trials for Mania
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine
Mania, Bipolar Disorder
RecruitingPhase 3
A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Bipolar Disorder Type I With Mania
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder
Bipolar-I Disorder With Mania or Mania With Mixed Features
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2)
Bipolar Disorder Type I With Mania or Mania With Mixed Features
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa DelBello, MD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Mania and Bipolar Disorder, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00893581, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2016.