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Brain Aging and Treatment Response in Geriatric Depression

Primary Purpose

Mild Cognitive Impairment (MCI), Depression

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Escitalopram

Memantine

Placebo

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment (MCI) focused on measuring 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

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Sites / Locations

UCLA Semel Institute - Neuropsychiatric Institute (NPI)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Escitalopram and Memantine

Escitalopram and placebo

Arm Description

Participants will take a combination of Escitalopram and Memantine for 12 months

Participants will take a combination of Escitalopram and placebo for 12 months

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT01902004

First Posted

May 31, 2013

Last Updated

October 11, 2019

Sponsor

University of California, Los Angeles

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT01902004

Brief Title

Brain Aging and Treatment Response in Geriatric Depression

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

October 2013 (Actual)

Primary Completion Date

January 23, 2019 (Actual)

Study Completion Date

January 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Los Angeles

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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, Disability, Comorbidity, Medical Burden, Safety, Candidate Genes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

115 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Escitalopram and Memantine

Arm Type

Active Comparator

Arm Description

Participants will take a combination of Escitalopram and Memantine for 12 months

Arm Title

Escitalopram and placebo

Arm Type

Active Comparator

Arm Description

Participants will take a combination of Escitalopram and placebo for 12 months

Intervention Type

Drug

Intervention Name(s)

Escitalopram

Other Intervention Name(s)

Lexapro

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Memantine

Other Intervention Name(s)

Namenda

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

inactive substance

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Hamilton Depression Rating Scale

Description

Time Frame

Measured at 3 months; 6 months and 12 months

Secondary Outcome Measure Information:

Title

Change in Montgomery Asberg Depression Rating Scale

Description

Time Frame

Measured at 3 months; 6 months and 12 months

Title

Change in Cognitive Domain Scores

Description

Time Frame

Measured at 6 months and 12 months

Other Pre-specified Outcome Measures:

Title

Number of Participants With Adverse Events

Description

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.

Time Frame

Measured at 3, 6 months and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Helen Lavretsky, M.D.

Organizational Affiliation

University of California, Los Angeles

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCLA Semel Institute - Neuropsychiatric Institute (NPI)

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35233974

Citation

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.

Results Reference

derived

PubMed Identifier

32663977

Citation

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.

Results Reference

derived

PubMed Identifier

32382137

Citation

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.

Results Reference

derived

PubMed Identifier

31519517

Citation

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.

Results Reference

derived

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Brain Aging and Treatment Response in Geriatric Depression

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