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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| levomilnacipran (FETZIMA) | Active Comparator | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| levomilnacipran | Drug | antidepressant |
|
|
| 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 |
| 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 |
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Inclusion Criteria:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Helen Lavretsky, M.D. | University of California, Los Angeles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Semel Institute - Neuropsychiatric Institute (NPI) | Los Angeles | California | 90095 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31332902 | Result | Krause-Sorio B, Kilpatrick L, Siddarth P, Ercoli L, Laird KT, Aguilar-Faustino Y, Milillo MM, Narr KL, Lavretsky H. Cortical thickness increases with levomilnacipran treatment in a pilot randomised double-blind placebo-controlled trial in late-life depression. Psychogeriatrics. 2020 Mar;20(2):140-148. doi: 10.1111/psyg.12475. Epub 2019 Jul 22. | |
| 33757609 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Levomilnacipran (FETZIMA) | 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. levomilnacipran: antidepressant |
| FG001 | Placebo | 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. Placebo: an inactive drug |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Levomilnacipran (FETZIMA) | 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. levomilnacipran: antidepressant |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 12 weeks |
|
09/2016 - 07/2018; 1 years and 10 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Levomilnacipran (FETZIMA) | 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. levomilnacipran: antidepressant |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Teeth grinding | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Helen Lavretsky, MD | UCLA | 310-794-4619 | HLavretsky@mednet.ucla.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 30, 2015 | Apr 8, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D003244 | Consciousness Disorders |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D019954 | Neurobehavioral Manifestations |
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| ID | Term |
|---|---|
| D000078862 | Levomilnacipran |
| ID | Term |
|---|---|
| D000078764 | Milnacipran |
| D003521 | Cyclopropanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| Placebo | Drug | an inactive drug |
|
|
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 |
| Lee SM, Dong TS, Krause-Sorio B, Siddarth P, Milillo MM, Lagishetty V, Datta T, Aguilar-Faustino Y, Jacobs JP, Lavretsky H. The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study. Int Psychogeriatr. 2022 Jan;34(1):33-45. doi: 10.1017/S1041610221000120. Epub 2021 Mar 24. |
| Placebo |
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. Placebo: an inactive drug |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Hamilton Depression Rating Scale Score | 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. | Mean | Standard Deviation | units on a scale |
|
| Placebo |
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. Placebo: an inactive drug |
|
|
| Secondary | 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]. | Posted | Mean | Standard Deviation | units on a scale | Week 12 reported |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline and 12 weeks |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 11 |
| 17 |
| EG001 | Placebo | 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. Placebo: an inactive drug | 0 | 12 | 0 | 12 | 2 | 12 |
| Sleepiness | Psychiatric disorders | Systematic Assessment |
|
| Decreased duration of sleep | Psychiatric disorders | Systematic Assessment |
|
| Reduced salivation | General disorders | Systematic Assessment |
|
| Sweating | General disorders | Systematic Assessment |
|
| Falls | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Upset stomach | Gastrointestinal disorders | Systematic Assessment |
|
| Micturition disturbance | Renal and urinary disorders | Systematic Assessment |
|
| Orthostatic dizziness | General disorders | Systematic Assessment |
|
| Orgastic dysfunction | Reproductive system and breast disorders | Systematic Assessment |
|
| Increased blood pressure | Cardiac disorders | Systematic Assessment |
|
| Heart palpitations/tachycardia | Cardiac disorders | Systematic Assessment |
|
| Visual disturbances | General disorders | Systematic Assessment |
|
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| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |