A Study of the Neurobiology of Depression

NCT01051466 | Completed Phase 4 Results

• 2 other identifiers: 12875F1J-US-HMGO
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Healthy Participants

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to 12-Week Endpoint in the Functional Magnetic Resonance Imaging (fMRI) Mean Blood Oxygenation-Level-Dependent (BOLD) Response in the Amygdalae

  Functional MRI or fMRI is a functional neuroimaging procedure that uses MRI technology to measure brain activity by detecting associated changes in blood flow. When an area of the brain is in use, blood flow to that region increases. The activation in response to the processing of sad faces was measured by the percentage of signal change in BOLD response from before to after sad faces processing. The percentage of signal change was calculated by taking the difference between BOLD response after sad faces processing and BOLD response before sad faces processing and dividing by BOLD response before sad face processing, then multiplying by 100. BOLD signals were measured using arbitrary magnetic resonance units. Amygdala BOLD activation was calculated as an average between the left amygdala activation and right amygdala activation. Least squares (LS) mean was calculated using mixed-model repeated measures (MMRM) adjusted for group, visit, group-by-visit, and baseline value.

  Baseline, Week 12

Secondary Outcomes (15)

• 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

  Baseline, Week 12

• Change From Baseline to 12-Week Endpoint in Volume of Subgenual Anterior Cingulate, Amygdalae, and Hippocampus

  Baseline, Week 12

• 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

  Baseline, Weeks 1, 8, and 12

• Gs Alpha (Gsα)-Activated Adenylyl Cyclase

  Baseline and Weeks 1, 8, and 12

• Change From Baseline to 12-Week Endpoint in Brain-Derived Neurotrophic Factor (BDNF) and the Precursor of BDNF (proBDNF)

  Baseline, Week 12

Study Arms (2)

Duloxetine

EXPERIMENTAL

Drug: Duloxetine

Healthy Participants

NO INTERVENTION

Interventions

Duloxetine DRUG

60 milligrams (mg) administered orally daily for 8 weeks then 60-120 mg if non remitter or 60 mg if remitter for 4 additional weeks

Also known as: Cymbalta, LY248686

Duloxetine

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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.

London, United Kingdom, SE5 8AF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25880400 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Three healthy participants were identified as not meeting inclusion/exclusion criteria after enrollment. They were discontinued and excluded from secondary outcome analyses, but included in participant flow, primary outcome analyses, and safety.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: January 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: October 10, 2014
• Results First Posted: April 2, 2014

Record last verified: 2014-10

Locations

GB (1)