Biomarkers of Antidepressant Treatment in Adolescents With Major Depression (The Adolescents MDD Study)
Primary Purpose
Major Depressive Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Fluoxetine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Fluoxetine, QEEG, cordance, ATR
Eligibility Criteria
Inclusion Criteria:
- Outpatients with non-psychotic, unipolar Major Depressive Disorder (MDD) based on the K-SADS-PL
- A score of ≥ 45 on the Children's Depression Rating Scale-Revised (same threshold as TADS). As with the TADS trial, depressed mood must have been present in at least 2 of 3 contexts (home, school, among peers) for at least 6 weeks prior to consent.
- Age range: 14-18.
- Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm.
Exclusion Criteria:
Subjects will have no unstable medical illness that would prevent completion of participation in the trial (determined as needed from physical examination, ECG, laboratory safety tests, as well as a review of systems). Other specific exclusionary criteria also are based on the BRITE-MD parameters, and include:
- mentally or legally incapacitated, unable to give informed consent;
- meets DSM-IV criteria for anorexia nervosa, bulimia nervosa, obsessive-compulsive disorder, any cognitive disorder, bipolar disorder, psychotic disorder, or major depression with psychotic features;
- MMSE (Folstein et al., 1975) score ≤ 24;
- evidence of drug dependency or substance abuse within the preceding nine months;
- stable and in remission on current psychotropic medication(s);
- any ECT within the past six months;
- failure to tolerate FLX or treatment failure with an adequate trial of FLX in the current episode;
- FLX would be contraindicated (e.g., hyponatremia with a prior SSRI);
- treatment with an MAOI within the past four weeks;
- any medical illness severe enough to significantly affect brain function or to interfere with interpretation of study results;
- history of seizures, brain surgery, skull fracture, significant head trauma, or abnormal EEG;
- psychiatric hospitalization indicated (e.g., imminent danger to self or others);
- initial QEEG recording is contaminated with artifact so that determination of the biomarker is precluded;
- use of medications known to affect brain function (e.g., antidepressants, anticonvulsants/mood stabilizers, anticholinergics, antipsychotics, benzodiazepines - same list as in BRITE-MD). Based on the TADS trial, we will also exclude for concurrent diagnoses of attention-deficit hyperactivity disorder managed with psychostimulants, pervasive developmental disorder, and mental retardation (mild, moderate, severe, or profound);
- subject is currently pregnant, or is of child-bearing potential and not using a medically acceptable means of birth control (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).
Sites / Locations
- UCLA Semel Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Fluoxetine
Placebo (PBO)
Arm Description
1 week single-blinded placebo lead-in and double-blinded FLX treatment for 8 weeks
Placebo treatment for 9 weeks of study
Outcomes
Primary Outcome Measures
Score on Children's Depression Rating Scale-Revised
Secondary Outcome Measures
Score on Hamilton Depression Rating Scale (HAM-D)
Full Information
NCT ID
NCT01185977
First Posted
April 6, 2010
Last Updated
July 2, 2014
Sponsor
University of California, Los Angeles
1. Study Identification
Unique Protocol Identification Number
NCT01185977
Brief Title
Biomarkers of Antidepressant Treatment in Adolescents With Major Depression (The Adolescents MDD Study)
Official Title
Biomarkers of Antidepressant Treatment in Adolescents With Major Depression
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will aim to evaluate the use of Electroencephalography (EEG) biomarkers in adolescent depression. Two specific hypotheses will be tested:
H1: Early decreases in prefrontal cordance values will be greater in responders to antidepressant therapy than in medication non-responders.
H2: Subjects with high Antidepressant Treatment Response(ATR) Index values [i.e., predicted to show symptomatic improvement with fluoxetine (FLX)] will achieve greater improvement in symptoms and in functional status than those with low ATR values.
Exploratory analyses will be undertaken to compare and contrast the cordance changes and ATR values in medication and placebo-treated responders and non-responders.
Detailed Description
A total of 26 adolescent subjects with Major Depressive Disorder(MDD), ages 12 to 20, will be consented and join this project at UCLA. For analytic purposes, we will define an "enrolled" subject as one who has completed the single-blind lead-in week and one week of double-blind treatment, and the three EEG recordings at these visits, as any subject who leaves the project prior to that point cannot contribute useful data to testing our hypotheses.
Subjects who enroll in this project will receive 1 week of single-blind placebo lead-in, followed by 8 weeks of double-blind randomized treatment either with fluoxetine (FLX), a Selective Serotonin Reuptake Inhibitor (SSRI) with FDA approval for use in this age group, or with placebo. Brain activity will be assessed with Qualitative EEG (QEEG) recording at pretreatment baseline, after lead-in, and at 1, 2, 4, and 8 weeks of treatment to expand the evidence base on the neurophysiology of treatment response in adolescents. Subjects will be assessed for symptom change, adverse events, and suicidality at each visit. Functional measures related to treatment will be assessed at baseline and at weeks 4 and 8. Subjects and the staff who interact with them will be blinded to QEEG biomarker values during the project.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Major Depressive Disorder, Fluoxetine, QEEG, cordance, ATR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fluoxetine
Arm Type
Active Comparator
Arm Description
1 week single-blinded placebo lead-in and double-blinded FLX treatment for 8 weeks
Arm Title
Placebo (PBO)
Arm Type
Placebo Comparator
Arm Description
Placebo treatment for 9 weeks of study
Intervention Type
Drug
Intervention Name(s)
Fluoxetine
Intervention Description
one-week single-blind PBO-lead-in phase, FLX 10 mg/d for 4 days then 20 mg/d of FLX thereafter
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One pill of PBO for 4 days then two pills of PBO thereafter
Primary Outcome Measure Information:
Title
Score on Children's Depression Rating Scale-Revised
Time Frame
Measured over 8 weeks
Secondary Outcome Measure Information:
Title
Score on Hamilton Depression Rating Scale (HAM-D)
Time Frame
Measured over 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Outpatients with non-psychotic, unipolar Major Depressive Disorder (MDD) based on the K-SADS-PL
A score of ≥ 45 on the Children's Depression Rating Scale-Revised (same threshold as TADS). As with the TADS trial, depressed mood must have been present in at least 2 of 3 contexts (home, school, among peers) for at least 6 weeks prior to consent.
Age range: 14-18.
Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm.
Exclusion Criteria:
Subjects will have no unstable medical illness that would prevent completion of participation in the trial (determined as needed from physical examination, ECG, laboratory safety tests, as well as a review of systems). Other specific exclusionary criteria also are based on the BRITE-MD parameters, and include:
mentally or legally incapacitated, unable to give informed consent;
meets DSM-IV criteria for anorexia nervosa, bulimia nervosa, obsessive-compulsive disorder, any cognitive disorder, bipolar disorder, psychotic disorder, or major depression with psychotic features;
MMSE (Folstein et al., 1975) score ≤ 24;
evidence of drug dependency or substance abuse within the preceding nine months;
stable and in remission on current psychotropic medication(s);
any ECT within the past six months;
failure to tolerate FLX or treatment failure with an adequate trial of FLX in the current episode;
FLX would be contraindicated (e.g., hyponatremia with a prior SSRI);
treatment with an MAOI within the past four weeks;
any medical illness severe enough to significantly affect brain function or to interfere with interpretation of study results;
history of seizures, brain surgery, skull fracture, significant head trauma, or abnormal EEG;
psychiatric hospitalization indicated (e.g., imminent danger to self or others);
initial QEEG recording is contaminated with artifact so that determination of the biomarker is precluded;
use of medications known to affect brain function (e.g., antidepressants, anticonvulsants/mood stabilizers, anticholinergics, antipsychotics, benzodiazepines - same list as in BRITE-MD). Based on the TADS trial, we will also exclude for concurrent diagnoses of attention-deficit hyperactivity disorder managed with psychostimulants, pervasive developmental disorder, and mental retardation (mild, moderate, severe, or profound);
subject is currently pregnant, or is of child-bearing potential and not using a medically acceptable means of birth control (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian A Cook, MD
Organizational Affiliation
Universityof California Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA Semel Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.DepressionLA.com
Description
Related Info
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Biomarkers of Antidepressant Treatment in Adolescents With Major Depression (The Adolescents MDD Study)
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