LMIL: Trial of Levomilnacipran in Geriatric Depression
Study Details
Study Description
Brief Summary
The purpose of this study is to examine the effects of levomilnacipran (FETZIMA) compared to placebo for the treatment of depression in older adults.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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. |
Drug: levomilnacipran
antidepressant
Other Names:
|
| Placebo Comparator: 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. |
Drug: Placebo
an inactive drug
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Hamilton Depression Rating Scale (HDRS) Scores 24 [Baseline and 12 weeks]
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.
Secondary Outcome Measures
- Clinical Global Impression Scale (CGI) Scores [Week 12 reported]
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].
- Geriatric Depression (GDS) Scores [Baseline and 12 weeks]
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.
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Semel Institute - Neuropsychiatric Institute (NPI) | Los Angeles | California | United States | 90095 |
Sponsors and Collaborators
- University of California, Los Angeles
Investigators
- Principal Investigator: Helen Lavretsky, M.D., University of California, Los Angeles
Study Documents (Full-Text)
More Information
Publications
None provided.- IIT-USA-000620
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Period Title: Overall Study | ||
| STARTED | 17 | 12 |
| COMPLETED | 7 | 9 |
| NOT COMPLETED | 10 | 3 |
Baseline Characteristics
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 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 | 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 | Total of all reporting groups |
| Overall Participants | 17 | 12 | 29 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
0
0%
|
4
33.3%
|
4
13.8%
|
| >=65 years |
17
100%
|
8
66.7%
|
25
86.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
73.24
(4.6)
|
69.08
(6.6)
|
71.5
(5.8)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
10
58.8%
|
8
66.7%
|
18
62.1%
|
| Male |
7
41.2%
|
4
33.3%
|
11
37.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
8.3%
|
1
3.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
5.9%
|
1
8.3%
|
2
6.9%
|
| White |
16
94.1%
|
8
66.7%
|
24
82.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
16.7%
|
2
6.9%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
17
100%
|
12
100%
|
29
100%
|
| Hamilton Depression Rating Scale Score (units on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [units on a scale] |
17.88
(2.5)
|
19.92
(2.6)
|
18.7
(2.7)
|
Outcome Measures
| Title | Hamilton Depression Rating Scale (HDRS) Scores 24 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 17 | 12 |
| Baseline |
17.88
(2.5)
|
19.92
(2.6)
|
| 12 Weeks |
6.86
(5.7)
|
10.33
(7.1)
|
| Title | Clinical Global Impression Scale (CGI) Scores |
|---|---|
| Description | 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]. |
| Time Frame | Week 12 reported |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 7 | 9 |
| Mean (Standard Deviation) [units on a scale] |
3.00
(.81)
|
3.33
(1.11)
|
| Title | Geriatric Depression (GDS) Scores |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo |
|---|---|---|
| Arm/Group Description | 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 | 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 |
| Measure Participants | 17 | 12 |
| Baseline |
13.5
(4.0)
|
15.33
(4.8)
|
| 12 Weeks |
11.71
(5.6)
|
11.33
(3.6)
|
Adverse Events
| Time Frame | 09/2016 - 07/2018; 1 years and 10 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Levomilnacipran (FETZIMA) | Placebo | ||
| Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
| Levomilnacipran (FETZIMA) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/12 (0%) | ||
Serious Adverse Events |
||||
| Levomilnacipran (FETZIMA) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/17 (0%) | 0/12 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Levomilnacipran (FETZIMA) | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/17 (64.7%) | 2/12 (16.7%) | ||
| Cardiac disorders | ||||
| Increased blood pressure | 1/17 (5.9%) | 1/12 (8.3%) | ||
| Heart palpitations/tachycardia | 3/17 (17.6%) | 0/12 (0%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 1/17 (5.9%) | 0/12 (0%) | ||
| Diarrhea | 1/17 (5.9%) | 0/12 (0%) | ||
| Constipation | 4/17 (23.5%) | 0/12 (0%) | ||
| Upset stomach | 1/17 (5.9%) | 0/12 (0%) | ||
| General disorders | ||||
| Reduced salivation | 2/17 (11.8%) | 1/12 (8.3%) | ||
| Sweating | 1/17 (5.9%) | 0/12 (0%) | ||
| Orthostatic dizziness | 1/17 (5.9%) | 1/12 (8.3%) | ||
| Visual disturbances | 1/17 (5.9%) | 0/12 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Teeth grinding | 3/17 (17.6%) | 0/12 (0%) | ||
| Falls | 1/17 (5.9%) | 0/12 (0%) | ||
| Psychiatric disorders | ||||
| Sleepiness | 1/17 (5.9%) | 0/12 (0%) | ||
| Decreased duration of sleep | 2/17 (11.8%) | 0/12 (0%) | ||
| Renal and urinary disorders | ||||
| Micturition disturbance | 6/17 (35.3%) | 0/12 (0%) | ||
| Reproductive system and breast disorders | ||||
| Orgastic dysfunction | 1/17 (5.9%) | 0/12 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Helen Lavretsky, MD |
|---|---|
| Organization | UCLA |
| Phone | 310-794-4619 |
| HLavretsky@mednet.ucla.edu |
- IIT-USA-000620