Mild Cognitive Impairment (MCI)Phase 4NCT01902004
Brain Aging and Treatment Response in Geriatric Depression
A Phase 4 study testing Escitalopram and Memantine in people with Mild Cognitive Impairment (MCI) and Depression, run by University of California, Los Angeles at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Mild Cognitive Impairment (MCI), Depression
- What is being tested?
- Escitalopram and Memantine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 115 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to 23 Jan 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
- Score of 16 or higher on the 24-item Hamilton Rating Scale for Depression (HDRS) at study entry
- Score of 24 or higher on the Mini-Mental State Exam (MMSE)
- Age 60 years old or older
Who cannot join
- History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
- Presence of psychotic symptoms
- Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
- Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
- Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
- Toxic or metabolic abnormalities on laboratory examination
Show all 19Show fewer
- Medications taken or medical illnesses present that could account for depression
- Active heart failure categorized as Class III or greater according to New York Heart Association criteria
- Heart attack or crescendo angina within the 3 months prior to study entry
- Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease
- Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds
- Second or third degree atrioventricular block
- Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry
- Treated with depot neuroleptic therapy within 6 months prior to study entry
- Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors [MAOIs]) prior to the first administration of study medication
- Known allergy to escitalopram or memantine or history of ineffective treatment with escitalopram or memantine for current depressive episode
- Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either escitalopram or memantine
- Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry
- Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Semel Institute - Neuropsychiatric Institute (NPI)
Los Angeles, California, 90095
About this study
Official title: Treatment of Geriatric Depression With Mild Cognitive Impairment: A Double-blind Placebo-Controlled Trial of Namenda (Memantine) Augmentation of Lexapro (Escitalopram) in Depressed Patients at Least 60 Years of Age
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.
Read the detailed description
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.
- Conditions
- Mild Cognitive Impairment (MCI), Depression
- Being tested
- Escitalopram, Memantine, Placebo
- Keywords
- Major Depression, Geriatric Major Depression, Executive Cognitive Dysfunction, Mild Cognitive Impairment, Older Adults, Geriatric, Executive Cognitive Impairment, Quality of Life, Disability, Comorbidity, Medical Burden, Safety, Candidate Genes
- Medical subject headings
- Cognitive Dysfunction, Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EscitalopramDrug
Also called Lexapro
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.
MemantineDrug
Also called Namenda
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.
PlaceboDrug
Also called inactive substance
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.
| Study group | Role | What they receive |
|---|---|---|
| Escitalopram and Memantine | Active comparator | Participants will take a combination of Escitalopram and Memantine for 12 months Receives: Drug: Escitalopram; Drug: Memantine |
| Escitalopram and placebo | Active comparator | Participants will take a combination of Escitalopram and placebo for 12 months Receives: Drug: Escitalopram; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured at 3 months; 6 months and 12 months
Secondary outcomes (2)
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.
Measured: 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: Measured at 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2013 (estimated)
- Study startOct 2013
- Primary completion23 Jan 2019
- Study completion23 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive Impairment (MCI)Studies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Helen Lavretsky, MD, University of California, Los Angeles
- Investigators
- Helen Lavretsky, M.D., Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01902004
- Sponsor's protocol ID
- R-01 MH097892
- Other IDs
- R01MH097892
- Status last verified
- Oct 2019
- First submitted
- 31 May 2013
- Last updated
- 15 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 35233974Krause-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.
PubMed 32663977Grzenda 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.
PubMed 32382137Lavretsky 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.
PubMed 31519517
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Geriatric Depression With Mild Cognitive Impairment: A Double-blind Placebo-Controlled Trial of Namenda (Memantine) Augmentation of Lexapro (Escitalopram) in Depressed Patients at Least 60 Years of Age
- ClinicalTrials.gov ID
- NCT01902004
- Acronym / sponsor ID
- R-01 MH097892
- Conditions
- Mild Cognitive Impairment (MCI), Depression
- Keywords
- Major Depression, Geriatric Major Depression, Executive Cognitive Dysfunction, Mild Cognitive Impairment, Older Adults, Geriatric, Executive Cognitive Impairment, Quality of Life
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 115 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2013 (actual)
- Primary completion
- 23 Jan 2019 (actual)
- Study completion
- 23 Jan 2019 (actual)
- First posted
- 17 Jul 2013 (estimated)
- Results
- Posted 15 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Escitalopram and Memantine | Active comparator | Drug: Escitalopram, Drug: MemantineParticipants will take a combination of Escitalopram and Memantine for 12 months |
| Escitalopram and placebo | Active comparator | Drug: Escitalopram, Drug: PlaceboParticipants will take a combination of Escitalopram and placebo for 12 months |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)
- Score of 16 or higher on the 24-item Hamilton Rating Scale for Depression (HDRS) at study entry
- Score of 24 or higher on the Mini-Mental State Exam (MMSE)
- Age 60 years old or older
Key exclusion criteria (19 listed)
- History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode
- Presence of psychotic symptoms
- Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry
- Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry
- Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EscitalopramAlso: LexaproAll 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. | Drug | Escitalopram and Memantine, Escitalopram and placebo |
| MemantineAlso: NamendaMemantine 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. | Drug | Escitalopram and Memantine |
| PlaceboAlso: inactive substancePlacebo 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. | Drug | Escitalopram and placebo |
Primary outcome
Change in Hamilton Depression Rating Scale
Time frame: Measured at 3 months; 6 months and 12 months
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.
2 secondary outcomes
Change in Montgomery Asberg Depression Rating Scale
Time frame: Measured at 3 months; 6 months and 12 months
Change in Cognitive Domain Scores
Time frame: Measured at 6 months and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35233974Kilpatrick 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.
- Derived from this study: PubMed 32663977Krause-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.
- Derived from this study: PubMed 32382137Grzenda 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.
- Derived from this study: PubMed 31519517Lavretsky 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Lavretsky, M.D. principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Escitalopram and Memantine in people with Mild Cognitive Impairment (MCI) and Depression, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hamilton Depression Rating Scale (time frame: Measured at 3 months; 6 months and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01902004, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2019.