Duloxetine for Chronic Depression: a Double-blind Study

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00360724
First received: August 3, 2006
Last updated: April 25, 2016
Last verified: October 2013
  Purpose

The investigators are studying a new antidepressant medicine, duloxetine, for the treatment of people with chronic depression. Duloxetine (trade name Cymbalta) was recently approved by the FDA for the treatment of major depression. The investigators are testing whether this medicine is also effective for adults with chronic depression (dysthymic disorder or dysthymia).

Chronic depression, lasting two or more years, often causes significant suffering and impairment. The investigators study involves a 6 to 10 week double-blind Initial Phase during which half of the participants will take the new medication and half will take a placebo (an inactive look-alike pill). After the Initial Phase, a 12-week Continuation Phase will begin, during which all subjects can be treated with an FDA-approved antidepressant medication.

Eligible subjects may also receive MRI scans, to help the investigators understand how antidepressants work in treating depression.


Condition Intervention Phase
Dysthymic Disorder
Depressive Disorder NOS
Drug: Duloxetine (Cymbalta)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Duloxetine for Chronic Depression: a Double-blind Study

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale (HDRS) - 24 Total Score [ Time Frame: Week 10 ] [ Designated as safety issue: Yes ]
    HDRS-24 total score, standardly used rating scale for depression. Score 0-7 no depression; Score 8-16 mild depression; Score 17-23 moderate depression; Score 24 and up severe depression. Range= 0 to 75, higher score=worse depression

  • Hamilton Depression Rating Scale (HDRS) - 24 Total Score [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    HDRS-24 total score, standardly used rating scale for depression. Score 0-7 no depression; Score 8-16 mild depression; Score 17-23 moderate depression; Score 24 and up severe depression. Range= 0 to 75, higher score=worse depression


Secondary Outcome Measures:
  • Cornell Dysthymia Rating Scale (CDRS) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

    CDRS is a 20-item clinician-rated inventory for chronic depressive symptoms. Each item was characterized by an explanatory or illustrative description and rated from 0 (symptom absent) to 4 (severe symptoms).

    Scores from 0 to 82 with higher score indicating worse depression


  • Global Assessment of Functioning Scale (GAF) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

    A commonly used rating scale for global social function.

    Range from 0 to 100; higher score=better functioning. 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 no more than slight impairment in social, occupational, or school functioning (e.g., temporarily falling behind in schoolwork).

    61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Some impairment in reality testing or communication 21 - 30 Behavior is considerably influenced by delusions or hallucinations or serious impairment, in communication or judgment 11 - 20 Some danger of hurting self or others

    1 - 10 Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death.

    0 Inadequate information


  • Beck Depression Inventory (BDI) [ Time Frame: Week 10 ] [ Designated as safety issue: No ]

    Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression.

    When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-offs are as follows:[7]

    0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.

    Higher total scores indicate more severe depressive symptoms.


  • Magnetic Resonance Imaging, Anatomical [ Time Frame: 10 weeks, 22 weeks ] [ Designated as safety issue: No ]
    1. Chronic depression vs. normal differences: we expect to find abnormal brain region volumes in several regions compared to norms. Specifically: Frontal Cortex: decreased dorsal prefrontal volume, and reduced grey matter in subgenual prefrontal cortex; reduced orbitofrontal cortex gray matter volume; decreased hippocampal volume; decreased amygdala volume; decreased caudate volume; decreased putamen volume
    2. treatment vs. placebo differences: following active treatment, we hypothesize that volumes will change in the direction of normal in the hippocampus, prefrontal cortex, subgenual cortex, and amygdala
    3. responder vs. non-responder differences: greater changes in the areas found in hypothesis 2 are expected in treatment responders compared to non-responders

  • Clinical Global Impressions Improvement(CGI-I) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

    The Clinical Global Impression - Improvement(CGI-I) is a 7-point scale that rate patient's total improvement whether or not comparing to his/her condition at baseline.

    0 = Not assessed

    1. = Very much improved
    2. = Much improved
    3. = Minimally improved
    4. = No change
    5. = Minimally worse
    6. = Much worse
    7. = Very much worse Higher score=greatest worsening

  • Magnetic Resonance Imaging, Functional (fMRI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

    Functional brain imaging tests, including measures of cognitive conflict (Simon Task) and affective activation (Affective circumplex task) fMRI

    a. Simon Task: i. We expect reduced frontal cortex activation in depressed subjects, and ii. normalization of frontal cortex activation following treatment. b. Affective Circumplex Task: i. Reduced amygdala and hippocampal activation in depressed subjects, ii. normalization of activation in these areas following treatment.


  • Magnetic Resonance Spectroscopic Imaging (MRSI) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Magnetic resonance spectroscopic imaging. We expect to find decreased levels of N-Acetyl-Aspartate (NAA) in frontal cortex (dorsal prefrontal, subgenual prefrontal cortex, and orbitofrontal cortex gray matter), as well as in hippocampus, amygdala, caudate, and putamen.

  • Cornell Dysthymia Rating Scale (CDRS) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    CDRS is a 20-item clinician-rated inventory for chronic depressive symptoms. Each item was characterized by an explanatory or illustrative description and rated from 0 (symptom absent) to 4 (severe symptoms).

    Scores from 0 to 82 with higher score indicating worse depression


  • Beck Depression Inventory (BDI) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression.

    When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-offs are as follows:[7]

    0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.

    Higher total scores indicate more severe depressive symptoms.


  • Global Assessment of Functioning Scale (GAF) [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    A commonly used rating scale for global social function.

    Range from 0 to 100; higher score=better functioning. 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 no more than slight impairment in social, occupational, or school functioning (e.g., temporarily falling behind in schoolwork).

    61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Some impairment in reality testing or communication 21 - 30 Behavior is considerably influenced by delusions or hallucinations or serious impairment, in communication or judgment 11 - 20 Some danger of hurting self or others

    1 - 10 Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death.

    0 Inadequate information



Enrollment: 65
Study Start Date: August 2006
Study Completion Date: December 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: duloxetine (cymbalta)
Duloxetine medication: a medication currently marketed in the USA that is reported to have pharmacological effects including reuptake blockage for serotonin and norepinephrine
Drug: Duloxetine (Cymbalta)
duloxetine medication up to dose of 120 mg/day
Other Names:
  • duloxetine
  • Cymbalta
Placebo Comparator: Placebo treatment
placebo treatment: treatment with placebo capsules that match active medication capsules
Drug: Duloxetine (Cymbalta)
duloxetine medication up to dose of 120 mg/day
Other Names:
  • duloxetine
  • Cymbalta

Detailed Description:

This is a 22-week study of the tolerability, dosing, and efficacy of duloxetine in chronically depressed outpatients. Participants can have Dysthymic Disorder (Dysthymia), or Depression, Not Otherwise Specified (Depression NOS).

The first 10 weeks (Acute Phase) are double blind, placebo-controlled, and the second 12 weeks (Continuation Phase) is open-label and all subjects will receive active medication.

Tests of cytokine functioning will be performed and analyzed for treatment and placebo effects.

In addition, a subset of patients will be enrolled into an Magnetic Resonance Imaging (MRI) sub-study, in which a variety of brain imaging techniques (including anatomical MRI, functional MRI (fMRI), MR Spectroscopy, and Diffusion Tensor Imaging) will be performed at baseline and week 10. Duloxetine responders will have a third MRI performed at week 22.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age 20 to 75 years (ages 20 to 60 for MRI sub-study)
  • diagnosis of dysthymic disorder (chronic depression) or depression NOS
  • minimum of 2 years duration of current episode of depression

Exclusion Criteria:

  • current major depression
  • diagnoses including delirium, dementia, bipolar disorder, schizophrenia
  • substance abuse or dependence in the past 6 months
  • pregnant or nursing women
  • serious risk of suicide
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360724

Locations
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Eli Lilly and Company
Investigators
Principal Investigator: David J. Hellerstein, MD New York State Psychiatric Institute
  More Information

Additional Information:
Publications:
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00360724     History of Changes
Other Study ID Numbers: # 4967/6363R 
Study First Received: August 3, 2006
Results First Received: October 1, 2013
Last Updated: April 25, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by New York State Psychiatric Institute:
dysthymia
dysthymic disorder
chronic depression
chronic low-grade depression
atypical depression
minor depression
depression NOS
depression
depressive disorder
mood disorder
unipolar depression
low-grade depression

Additional relevant MeSH terms:
Disease
Depression
Depressive Disorder
Dysthymic Disorder
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Duloxetine Hydrochloride
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents
Psychotropic Drugs
Dopamine Agents

ClinicalTrials.gov processed this record on August 23, 2016