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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH097892 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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The proposed project will evaluate the role of neuroimaging biomarkers of brain aging (i.e., neurodegenerative and vascular brain changes) and mild cognitive impairment in the patterns of treatment response to memantine combined with escitalopram compared to escitalopram and placebo.
This study is designed to conduct a double-blind placebo-controlled trial of Namenda (Memantine) as an augmentation to Lexapro (Escitalopram) in depressed older adults 60 years of age and older. Throughout the course of the study, the investigators anticipate screening about 400 subjects to recruit 134 participants in the first four years. This study will require that the subjects complete up to 20 (twenty) visits in 12 (twelve) months to the study site during their participation. The purpose of this study is to determine whether Namenda (memantine) when taken in combination with Lexapro (escitalopram), may improve the quality of treatment response by making it faster and more complete, and also by improving thinking and memory in comparison to Lexapro taken with a placebo. Enrolled subjects will be provided with 10-20 mg of escitalopram for 12 months, and concurrently randomly assigned to either memantine or placebo groups. The investigators will also examine the safety and tolerability (how well the treatment works and the side effects) of a combination of Namenda and Lexapro as compared to placebo and Lexapro in subjects with major depressive disorder and mild cognitive impairment who are at least 60 years of age. Memantine is likely to accelerate and enhance antidepressant response to escitalopram and improve cognitive performance. Subjects with amnestic mild cognitive impairment or biomarkers of brain aging at baseline are likely to have preferential response to the combination of memantine and escitalopram compared to escitalopram and placebo, thus identifying a more personalized treatment approach in the high-risk subgroups for poor clinical outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escitalopram and Memantine | Active Comparator | Participants will take a combination of Escitalopram and Memantine for 12 months |
|
| Escitalopram and placebo | Active Comparator | Participants will take a combination of Escitalopram and placebo for 12 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram | Drug | All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hamilton Depression Rating Scale | Clinician administered scale measures severity of depressive symptoms. 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. | Measured at 3 months; 6 months and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Montgomery Asberg Depression Rating Scale | Clinician administered item scale measures severity of depressive symptoms. The 10 items are measured on a 7-point scale ranging from 0 to 6; creating a total range of 0-60. A score of 0 suggests absence of symptoms and higher scores represent greater severity of depression.Severity gradations for the MADRS have been proposed (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe). Treatment remission is defined as an endpoint total score ≤ 10. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable. |
Inclusion Criteria:
Exclusion Criteria:
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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 |
|---|---|---|---|
| 35233974 | Derived | Kilpatrick LA, Krause-Sorio B, Siddarth P, Narr KL, Lavretsky H. Default mode network connectivity and treatment response in geriatric depression. Brain Behav. 2022 Apr;12(4):e2475. doi: 10.1002/brb3.2475. Epub 2022 Mar 1. | |
| 32663977 | Derived | Krause-Sorio B, Siddarth P, Kilpatrick L, Laird KT, Milillo MM, Ercoli L, Narr KL, Lavretsky H. Combined treatment with escitalopram and memantine increases gray matter volume and cortical thickness compared to escitalopram and placebo in a pilot study of geriatric depression. J Affect Disord. 2020 Sep 1;274:464-470. doi: 10.1016/j.jad.2020.05.092. Epub 2020 May 24. |
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A total of 20 participants were excluded after being consented and prior to randomization. 5 were determined to be ineligible after completing the in-person screen visit in which they were consented. 15 withdrew consent before being randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Escitalopram and Memantine | Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day. |
| FG001 | Escitalopram and Placebo | Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Escitalopram and Memantine | Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day. |
| 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 | Change in Hamilton Depression Rating Scale | Clinician administered scale measures severity of depressive symptoms. 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. | The number of participants with available data at each time point differs due to participant dropout over the course of the study. | Posted | Mean | Standard Deviation | units on a scale | Measured at 3 months; 6 months and 12 months |
|
1 year
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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 | Escitalopram and Memantine | Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Concentration Difficulties | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Helen Lavretsky | UCLA Semel Institute for Neuroscience and Human Behavior | (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 | Sep 19, 2018 | Sep 24, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| D008559 | Memantine |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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|
|
| Memantine | Drug | Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day. |
|
|
| Placebo | Drug | Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day. |
|
|
| Measured at 3 months; 6 months and 12 months |
| Change in Cognitive Domain Scores | Neuropsychological battery of tests which included the following domains: learning, delayed recall, and executive functioning. Raw scores were transformed to z-scores for each test score of interest for each participant, and then averaged. These z-scores were averaged within each neuropsychological domain to produce composite scores and then averaged over all tests to calculate a global performance score. Higher scores are indicative of better performance. | Measured at 6 months and 12 months |
| Measured at 3, 6 months and 12 months |
| 32382137 | Derived | Grzenda A, Siddarth P, Laird KT, Yeargin J, Lavretsky H. Transcriptomic signatures of treatment response to the combination of escitalopram and memantine or placebo in late-life depression. Mol Psychiatry. 2021 Sep;26(9):5171-5179. doi: 10.1038/s41380-020-0752-2. Epub 2020 May 7. |
| 31519517 | Derived | Lavretsky H, Laird KT, Krause-Sorio B, Heimberg BF, Yeargin J, Grzenda A, Wu P, Thana-Udom K, Ercoli LM, Siddarth P. A Randomized Double-Blind Placebo-Controlled Trial of Combined Escitalopram and Memantine for Older Adults With Major Depression and Subjective Memory Complaints. Am J Geriatr Psychiatry. 2020 Feb;28(2):178-190. doi: 10.1016/j.jagp.2019.08.011. Epub 2019 Aug 22. |
| BG001 | Escitalopram and Placebo | Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hamilton Depression Rating Scale Score | Clinician administered scale measures severity of depressive symptoms. 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 |
|
| OG001 | Escitalopram and Placebo | Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day. |
|
|
| Secondary | Change in Montgomery Asberg Depression Rating Scale | Clinician administered item scale measures severity of depressive symptoms. The 10 items are measured on a 7-point scale ranging from 0 to 6; creating a total range of 0-60. A score of 0 suggests absence of symptoms and higher scores represent greater severity of depression.Severity gradations for the MADRS have been proposed (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe). Treatment remission is defined as an endpoint total score ≤ 10. | The number of participants with available data at each time point differs due to participant dropout over the course of the study. | Posted | Mean | Standard Deviation | units on a scale | Measured at 3 months; 6 months and 12 months |
|
|
|
| Secondary | Change in Cognitive Domain Scores | Neuropsychological battery of tests which included the following domains: learning, delayed recall, and executive functioning. Raw scores were transformed to z-scores for each test score of interest for each participant, and then averaged. These z-scores were averaged within each neuropsychological domain to produce composite scores and then averaged over all tests to calculate a global performance score. Higher scores are indicative of better performance. | The number of participants with available data at each time point differs due to participant dropout over the course of the study. | Posted | Mean | Standard Deviation | z score | Measured at 6 months and 12 months |
|
|
|
| Other Pre-specified | Number of Participants With Adverse Events | The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable. | The number of participants with available data at each time point differs due to participant dropout over the course of the study. | Posted | Count of Participants | Participants | Measured at 3, 6 months and 12 months |
|
|
|
| 0 |
| 48 |
| 0 |
| 48 |
| 41 |
| 48 |
| EG001 | Escitalopram and Placebo | Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day. | 0 | 47 | 0 | 47 | 41 | 47 |
| Asthenia/Lassitude/Increased Fatigability | Psychiatric disorders | Non-systematic Assessment |
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| Sleepiness/Sedation | Psychiatric disorders | Non-systematic Assessment |
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| Failing Memory | Nervous system disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
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| Tension/Inner Unrest | Psychiatric disorders | Non-systematic Assessment |
|
| Increased Duration of Sleep | Psychiatric disorders | Non-systematic Assessment |
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| Reduced Duration of Sleep | Psychiatric disorders | Non-systematic Assessment |
|
| Increased Dream Activity | Psychiatric disorders | Non-systematic Assessment |
|
| Accomodation Disturbance | Eye disorders | Non-systematic Assessment |
|
| Increased Salivation | General disorders | Non-systematic Assessment |
|
| Reduced Salivation | General disorders | Non-systematic Assessment |
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| Nausea/Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| Micturtion Disturbances | Renal and urinary disorders | Non-systematic Assessment |
|
| Polyuria/Polydipsia | Renal and urinary disorders | Non-systematic Assessment |
|
| Orthostatic Dizziness | General disorders | Non-systematic Assessment |
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| Palpitations/Tachycardia | Cardiac disorders | Non-systematic Assessment |
|
| Increased Tendancy to Sweating | General disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Weight Gain | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Diminished Sexual Drive | Reproductive system and breast disorders | Non-systematic Assessment |
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| Erectile Dysfunction | Reproductive system and breast disorders | Non-systematic Assessment |
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| Ejaculatory Dysfunction | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Orgastic Dysfunction | Reproductive system and breast disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
|
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| D001519 |
| Behavior |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| 3 Months |
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| 6 Months |
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| 12 Months |
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| 6 Months |
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| 12 Months |
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| 6 Months |
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| 12 Months |
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