Trial of Levomilnacipran in Geriatric Depression

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of levomilnacipran (FETZIMA) compared to placebo for the treatment of depression in older adults.

Detailed Description
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A 12-week pilot double-blind comparison of levomilnacipran (FETZIMA) to placebo for the treatment of geriatric depression. The investigators are interested in assessing the efficacy of levomilnacipran (LMIL) to placebo (PBO), and exploring the effects of antidepressant response on brain connectivity and neuroplasticity. This pilot study is designed to determine any differences in the efficacy, safety and tolerability of levomilnacipran compared to placebo, and to perform dose finding (20-120 mg per day) in 40 older depressed adults. The investigators anticipate that the LMIL will be superior to PBO in improving levels of depressive symptoms and rates of remission, as well as improving cognition, apathy, and quality of life. This proposal expands the investigator's focus on the biomarkers of neuroplasticity that have been used in several prior studies and demonstrated responsivity to antidepressant treatment. The purpose is to examine this directly in 40 older adults with major depression. This proposed trial will also serve as a pilot study to estimate the efficacy and tolerability of the drug in older depressed adults, and the dose-finding in this population.

Official Title
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Double-blind Placebo-controlled Trial of Levomilnacipran in Geriatric Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: levomilnacipran
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 60 years of age or older The presence of a major depressive disorder diagnosed according to the Diagnostic and Statistical Manual and Mental Disorders, 5th edition (DSM-V) criteria A 24-item Hamilton Rating Scale for Depression (HAMD) score of 16 or higher at baseline Mini-Mental State Exam (MMSE) score > 24. Exclusion Criteria: Subjects will be excluded if they had 1) any current and/or lifetime history of other psychiatric disorders (except unipolar depression with or without comorbid generalized anxiety disorder), or 2) recent unstable medical or neurological disorders; 3) any disabilities preventing participation in the study or in the MRI; 4) diagnosis of dementia; 5) acute suicidality; 6) subjects with known allergic reactions to milnacipran, uncontrolled narrow angle glaucoma, seizures, poorly-controlled hypertension or ischemic changes on ECG, serotonin syndrome, or the recently used monoamine oxidase inhibitors (MAOIs) within last 4 weeks; 7) ineligible for MRI (e.g., metal in the body or claustrophobia)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: levomilnacipran (FETZIMA)<br>All eligible subjects will be randomized to levomilnacipran or placebo group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. | Drug: levomilnacipran<br>* antidepressant<br>* Other names: FETZIMA;|
| Placebo Comparator: Placebo<br>All eligible subjects will be randomized to levomilnacipran or placebo group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. | Drug: Placebo<br>* an inactive drug<br>* Other names: inactive substance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HDRS) Scores 24 | This measure includes 24 items. Response options vary item to item and include the following ranges: [0-2], [0-3], and [0-4]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range [0-74], higher scores representing more severe difficulties. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression Scale (CGI) Scores | 7-Point Likert Scale [1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse]. | Week 12 reported | 
| Geriatric Depression (GDS) Scores | The GDS has a total of 30 items with response options [Yes/No]. Total score range is [0-30]. Higher scores represent more severe difficulties. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depressed, older adults, antidepressants, depression, MDD