Clinical trial NCT01051466: A Study of the Neurobiology of Depression
Official title: Neurobiological Correlates of Antidepressant Response After Duloxetine Hydrochloride Treatment in Subjects With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Healthy Participants
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-01-18
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Previous research studies have shown that depression is associated with changes in structure and activity in different parts of the brain and that antidepressant medication can affect brain activity in different parts of the brain in individuals suffering from depression. The primary purpose of the study is to find out more about how the antidepressant medication duloxetine affects brain activity and structure in individuals with depression.

Detailed description: This study will evaluate participants with depression before treatment is initiated and during treatment, and compare them to a control group of healthy participants. The aim will be to better understand both the neurobiology of depression and how the neurobiology changes in response to treatment of depression and the outcome of treatment. The study will include a variety of assessments of the neurobiology of depression including: scans of brain areas are involved in depression by looking at structures in the brain and how they work and blood tests and how these change in relation to several measures of depression severity.

Eligibility criteria: Inclusion Criteria:

Major Depressive Disorder (MDD) participants:

* Are right-handed
* Meet criteria for single episode or recurrent MDD, without psychotic features, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and confirmed by Structured Clinical Interview for DSM-IV-TR (SCID-IV), without co-morbid DSM-IV Axis I or II disorder at screening
* Be free of current antidepressant medication for a minimum of 6 weeks for fluoxetine treatment or of 4 weeks of other antidepressant treatment
* Have a 17-item Hamilton Depression Rating Scale (HAMD17) total score of ≥18 at screening, and baseline
* Women of child-bearing potential must have negative urine pregnancy tests prior to enrollment and agree to use a reliable method of birth control during the study

Healthy Participants

* Are right-handed
* Have a HAMD17 total score of \<7 at screening and baseline and must not meet the criteria for MDD based on the SCID-IV

Exclusion Criteria:

MDD participants and healthy participants:

* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device
* Treatment within the last 30 days with a drug that has not received regulatory approval
* Have previously completed or withdrawn from this study or any other study investigating duloxetine
* Have a history of substance abuse or dependence within the past 6 months
* A positive urine drug screen for any substances of abuse or dependence
* Have any current DSM-IV-TR co-morbid Axis I or II disorder as determined by participant's history or investigator assessment
* Have any history of bipolar disorder, a primary psychotic disorder (schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder), known Alzheimer's disease or mental retardation, or obsessive-compulsive disorder as determined by participant's history or investigator assessment
* Pregnant women, women who are breast-feeding, or women of childbearing potential who are not using a medically accepted means of contraception when engaging in sexual intercourse or have been surgically sterilized
* Are judged by the investigator to have serious suicidal risk or risk of self-harm
* Have a history of recurrent self-mutilation or self-harm
* Have uncontrolled narrow-angle glaucoma
* Have been diagnosed with an acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C)
* Have end-stage renal disease, a prior renal transplant, current renal dialysis, or severe renal impairment
* Have abnormal thyroid-stimulating hormone (TSH) concentration
* Have had electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or vagus nerve stimulation (VNS) within the past year
* Initiating psychotherapy within 6 weeks prior to study entry or during study participation, stopping, or changing psychotherapy after study entry
* Have frequent and/or severe allergic reactions with multiple medications, or known allergic reactions to the study medication
* Known hypersensitivity to duloxetine or any of the inactive ingredients
* Lack of response of the current episode to two or more adequate courses of antidepressant therapy at a clinically appropriate dose for a minimum of 4 weeks or in the judgment of the investigator the participant meets criteria for treatment-resistant depression
* Known human immunodeficiency virus (HIV) and other medical disorders that are known to affect central nervous system (CNS) structures or function as assessed by the investigator (for example, CNS neoplasms, neurosyphilis)
* Have a medical illness, a clinically significant laboratory abnormality, or is taking a CNS active medication that, in the opinion of the investigator, might interfere with study participation (for example, is likely to require hospitalization) or that, in the opinion of the investigator, might interfere with the interpretation of the primary endpoint (for example, hypertension or diabetes)
* Are unwilling or unable to comply with the study procedures

Primary outcomes:
measure: Change From Baseline to 12-Week Endpoint in the Functional Magnetic Resonance Imaging (fMRI) Mean Blood Oxygenation-Level-Dependent (BOLD) Response in the Amygdalae
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline to 12-Week Endpoint in Activation [Blood Oxygenation-Level-Dependent (BOLD) Response to Implicit Processing of Sad Faces] for Each of the 3 Brain Regions
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus
timeFrame: Baseline, Week 12
measure: Translocation of Gs Alpha (Gsα) From Lipid Rafts in the Cell Membranes of Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets Compared With Baseline
timeFrame: Baseline, Weeks 1, 8, and 12
measure: Gs Alpha (Gsα)-Activated Adenylyl Cyclase
timeFrame: Baseline and Weeks 1, 8, and 12
measure: Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF)
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF) Receptors
timeFrame: Baseline, Week 12
measure: Change From Baseline to 12-Week Endpoint in Proinflammatory Cytokines [Tumor Necrosis Factor Alpha (TNFα), Interleukin 1 (IL-1), and Interleukin 6 (IL-6)]
timeFrame: Baseline, Week 12
measure: 17-Item Hamilton Depression Rating Scale (HAMD17)
timeFrame: Baseline and up to Week 12
measure: Percentage of Participants With 17-Item Hamilton Depression Rating Scale (HAMD17) Response
timeFrame: Baseline, up to Week 12
measure: Percentage of Participants With 17-Item Hamilton Depression Rating Scale (HAMD17) Remission
timeFrame: Baseline, up to Week 12
measure: Sheehan Disability Scale (SDS)
timeFrame: Baseline and up to Week 12
measure: Clinical Global Impressions of Severity Scale (CGI-S)
timeFrame: Baseline and up to Week 12
measure: Patient's Global Impressions of Improvement (PGI-I) Scale
timeFrame: Baseline, up to Week 12
measure: Hamilton Anxiety Rating Scale (HAMA)
timeFrame: Baseline and up to Week 12
measure: Incidence of Suicidal Behavior and Suicidal Ideation as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline through Week 12
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Fu CH, Costafreda SG, Sankar A, Adams TM, Rasenick MM, Liu P, Donati R, Maglanoc LA, Horton P, Marangell LB. Multimodal functional and structural neuroimaging investigation of major depressive disorder following treatment with duloxetine. BMC Psychiatry. 2015 Apr 14;15:82. doi: 10.1186/s12888-015-0457-2.