Brain Aging and Treatment Response in Geriatric Depression

NCT01902004 | Completed Phase 4 Results DMC

• 2 other identifiers: R-01 MH097892R01MH097892
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

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.

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; Disability; Comorbidity; Medical Burden; Safety; Candidate Genes

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change in Montgomery Asberg Depression Rating Scale

  Measured at 3 months; 6 months and 12 months

• Change in Cognitive Domain Scores

  Measured at 6 months and 12 months

Other Outcomes (1)

• Number of Participants With Adverse Events

  Measured at 3, 6 months and 12 months

Study Arms (2)

Escitalopram and Memantine

ACTIVE COMPARATOR

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

Drug: Escitalopram; Drug: Memantine

Escitalopram and placebo

ACTIVE COMPARATOR

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

Drug: Escitalopram; Drug: Placebo

Interventions

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.

Also known as: Lexapro

Escitalopram and Memantine; Escitalopram and placebo

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.

Also known as: Namenda

Escitalopram and Memantine

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.

Also known as: inactive substance

Escitalopram and placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UCLA Semel Institute - Neuropsychiatric Institute (NPI)

Los Angeles, California, 90095, United States

Location

Related Publications (4)

• 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.

  PMID: 35233974 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.

  PMID: 32663977 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.

  PMID: 32382137 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.

  PMID: 31519517 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Depression; Depressive Disorder, Major

Interventions

Escitalopram; Memantine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Helen Lavretsky
• Organization: UCLA Semel Institute for Neuroscience and Human Behavior

hlavretsky@mednet.ucla.edu

(310)794-4619

Study Officials

• Helen Lavretsky, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 31, 2013
• First Posted: July 17, 2013
• Study Start: October 1, 2013
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: October 15, 2019
• Results First Posted: October 15, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)