Major depressive disorder MedDRA version: 14.1 Level: LLT Classification code 10025453 Term: Major depressive disorder NOS System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: Cymbalta
Product Name: duloxetine
Product Code: LY248686
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: MDD subjects are eligible to be included in the study only if they meet all of the following criteria: [1] Male or female outpatients at least 25 to 65 years of age that are right-handed. [2] Be able to comprehend the nature of the planned investigation and communicate intelligibly with the investigator and study coordinator. Have the capacity to sign the ICD. [3] Have signed the study ICD prior to any additional study procedures and after being informed of the study drug and procedures used in this study. [4] Meet the criteria for single episode or recurrent MDD, without psychotic features, as defined by the DSM-IV-TR and confirmed by SCID-IV, without co-morbid DSM-IV Axis I or II disorder. [5] Be free of their current antidepressant medication for a minimum of 6 weeks for fluoxetine treatment or of 4 weeks of other antidepressant treatment before start of study medication at Visit 2 (baseline). [6] Have a HAMD17 total score of =18 at Visits 1 and 2. [7] Judged to be a reliable study participant, and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol. [8] Agree not to participate in any other research trial or study while enrolled in this study. [9] Female subjects: Women of child-bearing potential must have negative urine pregnancy tests prior to enrollment (Visit 2) and agree to use a reliable method of birth control during the study. Healthy control subjects will be matched by age, gender, and IQ to subjects with MDD (group-matched). To meet the inclusion criteria for the study, healthy controls must have a HAMD17 total score of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: MDD subjects and healthy controls will be excluded from the study if they meet any of the following criteria: [10] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [11] Are Lilly employees. [12] 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 (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [13] Treatment within the last 30 days with a drug that has not received regulatory approval at the time of study entry. [14] Have previously completed or withdrawn from this study or any other study investigating duloxetine after receiving study drug. (Note: Subjects who have been previously screened for any duloxetine study including this study and never received study drug will be eligible for this study if they meet all current entry criteria.) [15] Have a history of substance abuse or dependence within the past 6 months (drug categories defined in the DSM-IV-TR), excluding nicotine and caffeine. [16] A positive urine drug screen for any substances of abuse or dependence. Note: In the case of a positive urine drug screen, in the opinion of the investigator, the investigator may follow-up with the Lilly clinical research physician/scientist for inclusion into the study [17] Have any current (within the past 6 months) DSM-IV-TR co-morbid Axis I or II disorder as determined by patient history or investigator assessment. [18] 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 patient history or investigator assessment. [19] 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 (for example, abstinence, intrauterine device, oral contraceptive, implant, Depo-Provera®, or barrier devices). [20] Are judged by the investigator to have serious suicidal risk or risk of self-harm. [21] Have a history of recurrent self-mutilation or self-harm. [22] Have uncontrolled narrow-angle glaucoma. [23] Have been diagnosed with an acute liver injury (such as hepatitis) or severe cirrhosis (Child-Pugh Class C). [24] Have end-stage renal disease, a prior renal transplant, current renal dialysis, or severe renal impairment. [25] Have abnormal thyroid-stimulating hormone (TSH) concentration. (Note: Subjects previously diagnosed with hyperthyroidism or hypothyroidism who have been treated on a stable dose of thyroid supplement for at least 3 months, have medically appropriate TSH concentrations and are clinically euthyroid, and are otherwise determined to be medically appropriate for study participation by t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine if duloxetine 60-120 mg given orally once daily (QD) for 12 weeks will result in changes in amygdalae activation (average of right and left amygdalae) in response to implicit sad facial affect processing in subjects with MDD from Week 0 (Visit 2) (baseline/medication-free) to Week 12 (endpoint) when compared with healthy control subjects, as assessed by the change in the fMRI mean blood-oxygenation-level-dependent (BOLD) response.; Secondary Objective: The secondary objectives of the study are: • Neuroimaging Correlates: to examine if changes in (1) anterior cingulate activation and volume and (2)amygdalae activation and volume predict remission (3) have diagnostic potential • Molecular and Cellular Correlates: 4. translocation of Gsa from lipid rafts 5. Gsa-activated adenylyl cyclase 6. if change in Gsa-activated adenylyl cyclase correlates with translocation of Gsa from lipid rafts 7. Gsa localization and adenylyl cyclase 8. changes in BDNF, proBDNF and their receptors 9. changes in proinflammatory cytokines • Clinical Measures and Outcome: 10. Change in clinical outcome from Week 0 to Week 12, as assessed by: a. Remission b. Response 11. change in the SDS 12. effects of treatment on other clinical outcomes 13. safety and tolerability during the 12-week open-label period ;Primary end point(s): Anterior cingulate and amygdalae activation in response to implicit sad facial affect processing will be measured by fMRI measurement, the percentage signal change from baseline task (neutral faces) to experimental task (sad faces) in BOLD response. The primary analysis is to test the null hypothesis that the me | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluation of neuroimaging and its correlation with changes in biomarkers, changes in clinical data and measures of anxiety and depression. Safety will also be assessed by monitoring adverse events, clinical signs and suicide ideation.;Timepoint(s) of evaluation of this end point: Up to 14 weeks | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Information
Eli Lilly & Company
Outcome results
None listed