Neural Mechanisms of Monoaminergic Engagement in Late-life Depression Treatment Response (NEMO)

NCT03128021 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: STUDY19120137R01MH076079
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The Department of Psychiatry at the University of Pittsburgh is conducting a research study to learn about the changes that occur in the brain when individuals suffer from and then are treated for depression. The NEMO study has two main purposes. The first is to provide medication treatment to individuals ages 60 and older who are currently depressed. The second part of the study involves completing a series of 4 MRIs, which assess changes in brain function over the course of treatment. This research may help investigators to develop faster and more effective treatment plans in the future, as brain responses that are detected early in treatment may predict how well an individual will respond to antidepressant medication.

Conditions

Major Depressive Disorder

Keywords

Depression; fMRI; Escitalopram; Lexapro; Randomized Clinical Trial; Levomilnacipran; Fetzima

Outcome Measures

Primary Outcomes (2)

• Change in Montgomery Asberg Depression Rating Scale Score

  Treatment response will be defined as either a MADRS score of less than 12 or 30% or greater reduction in MADRS score.

  Change in Baseline MADRS score through Week 12

• Change in Functional Connectivity

  The primary analysis will consist of linear mixed effects models with functional connectivity (for each region of interest) as the outcome measure and group (R \[responder\]/NR\[non-responder\], as defined by MADRS), time and their interaction. The results listed are the difference in Baseline to 12 hours after first dose of medication. The values derived by first preprocessing the raw data using SPM and using the AAL3 atlas to parcellate the images into anatomical brain regions. Then the mean residual time series for each region was calculated and the Pearson correlation between the time series of each region was calculated. Then the mean Pearson correlations between every other region with the region identified were calculated and these correlation values were then standardized to have a mean of 0 and a standard deviation of 1. Higher values indicate stronger and better connectivity.

  Change in Functional Connectivity from Baseline to Day 1

Secondary Outcomes (7)

• Response Styles Questionnaire- Rumination (RSQ-Rumination)

  Baseline, Week 1, and Week 12

• Hamilton Anxiety Rating Scale (HARS)

  Baseline, Week 1, and Week 12

• Neuropsychological Evaluations

  Baseline and Week 12

• Antidepressant Treatment History Questionnaire (ATHF)

  Baseline

• Medication Plasma Levels

  Weeks 1-12

Study Arms (4)

Escitalopram Pill

ACTIVE COMPARATOR

Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.

Drug: Escitalopram Pill

Placebo

PLACEBO COMPARATOR

Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability. Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.

Other: Placebo

Escitalopram Pill (Phase II)

OTHER

Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II. Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily. Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.

Drug: Escitalopram Pill

Levomilnacipran Pill

ACTIVE COMPARATOR

Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.

Drug: Levomilnacipran Pill

Interventions

Escitalopram Pill DRUG

Double-blinded, randomly assigned

Also known as: Lexapro

Escitalopram Pill; Escitalopram Pill (Phase II)

Placebo OTHER

Double-blinded, randomly assigned

Placebo

Levomilnacipran Pill DRUG

Double-blinded, randomly assigned

Also known as: Fetzima

Levomilnacipran Pill

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 60 years old
• Current Major Depressive Episode or Current Depressive Disorder Not Otherwise Specified or Dysthymic Disorder
• Montgomery-Asberg Depression Rating Scale (MADRS) greater than or equal to 12
• Modified Mini-Mental State (3MS) score greater than or equal to 84
• MoCA-BLIND greater than or equal to 13

You may not qualify if:

• History of Mania or Psychosis
• Current suicidal ideation that cannot be safely managed within the confines of a clinical trial
• Alcohol or Substance Abuse (current or past 3 months) endorsed via phone screening interview or diagnosed by Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID)
• Dementia of any etiology endorsed via phone screening interview or diagnosed by SCID
• Medical conditions with known significant effects on mood (e.g., stroke, current hypothyroid state) as well as unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cardiovascular risk factors that are not under medical management Unwilling or clinically determined to be unable to taper from high doses of benzodiazepines (equivalent to \> 2 mg lorazepam/day) or other anti-depressant/anti-anxiety medications at time of screening. However, for participants who are prescribed low dose psychotropics for pain, sleep disturbances, and/or medical conditions (e.g. amitriptyline for peripheral neuropathy, low dose trazodone as a sleep aid), these will be allowed in most circumstances. We will include participants on certain dosages of the most commonly prescribed antidepressants (for medical reasons) as follows: amitriptyline up to 50 mg/d, doxepin up to 50 mg/d, trazodone up to 100 mg/d, and imipramine up to 50 mg/d. Participants will also be able to continue taking buspirone, an antianxiety medication. As per the examples above, the PI will decide if the participants are eligible for the study and if they may continue the current medication. Justification regarding all decisions will be documented in the research record.
• Inability to complete required assessments including brain MRI and blood draw
• Hearing/vision impairment precluding neuropsychological testing
• Difficulty conversing in English
• Clinical contraindication to use of escitalopram or levomilnacipran or history of treatment resistance to escitalopram or levomilnacipran
• Unable or unwilling to provide a secondary/emergency contact person
• History of stroke with residual symptoms, current epilepsy, or current post-concussive symptoms
• Clinically relevant hyponatremia (below 130 mEq/L)
• Significant renal impairment

Sponsors & Collaborators

• Howard Aizenstein: lead
• Weill Cornell Institute of Geriatric Psychiatry: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (5)

• Andreescu C, Reynolds CF 3rd. Late-life depression: evidence-based treatment and promising new directions for research and clinical practice. Psychiatr Clin North Am. 2011 Jun;34(2):335-55, vii-iii. doi: 10.1016/j.psc.2011.02.005.

  PMID: 21536162 BACKGROUND

• Delis DC, Kaplan, E., Kramer, J.H. Delis Kaplan Executive Funciton System Examiner's Manual. The Psychological Corporation; 2001.

  BACKGROUND

• Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998 Jun;20(3):310-9. doi: 10.1076/jcen.20.3.310.823.

  PMID: 9845158 BACKGROUND

• Tomaszewski Farias S, Mungas D, Harvey DJ, Simmons A, Reed BR, Decarli C. The measurement of everyday cognition: development and validation of a short form of the Everyday Cognition scales. Alzheimers Dement. 2011 Nov;7(6):593-601. doi: 10.1016/j.jalz.2011.02.007.

  PMID: 22055976 BACKGROUND

• Isella V, Villa L, Russo A, Regazzoni R, Ferrarese C, Appollonio IM. Discriminative and predictive power of an informant report in mild cognitive impairment. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):166-71. doi: 10.1136/jnnp.2005.069765.

  PMID: 16421116 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Levomilnacipran

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Milnacipran; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Rachel Berta
• Organization: University of Pittsburgh

goodra@upmc.edu

4128607406

Study Officials

• Howard J Aizenstein, MD, Ph.D.

  Charles F. Reynolds III and Ellen G. Detlefsen Endowed Chair in Geriatric Psychiatry and Associate Professor of Bioengineering and Clinical and Translational Science

  PRINCIPAL INVESTIGATOR

• Carmen Andreescu, MD

  Assistant Professor of Psychiatry

  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
• Masking Details: Although this is a double-blinded study, one staff member will be unblinded regarding study randomization. Should the need ever arise, the blind can be instantly broken for the participant's safety and well-being.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Charles F. Reynolds III and Ellen G. Detlefsen Endowed Chair in Geriatric Psychiatry and Associate Professor of Bioengineering and Clinical and Translational Science

Model Details: Participants will be randomly assigned to take either escitalopram or levomilnacipran throughout the 12-week trial. The following information applies to the original study design. Enrollment according to this design was complete as of April 2018: During Phase I, participants will be randomly assigned to take escitalopram or placebo daily for 6 weeks. After 6 weeks, participants who are randomly assigned to placebo will be given the option to have an open-label of escitalopram for Phase II. Those who did not respond to escitalopram in Phase I will be referred for alternate treatment. All participants, regardless of outcome will be asked to return for follow-up procedures.

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 25, 2017
• Study Start: May 24, 2017
• Primary Completion: June 21, 2023
• Study Completion: August 30, 2023
• Last Updated: March 10, 2025
• Results First Posted: March 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data collected to date is submitted twice annually (January and July) and is shared within 4 months of submission.
• Access Criteria: NIH will provide access to scientific investigators for research purposes.

Locations

US (1)