Leveraging EEG for Antidepressant Prediction With Sertraline and Escitalopram (LEAP-SE)

Leveraging EEG for Antidepressant Prediction With Sertraline and Escitalopram (LEAP-SE): A Multicenter, Randomized, Blinded Outcome Study of EEG-guided Treatment With Sertraline Versus Escitalopram in Adults With Major Depressive Disorder

The LEAP-SE study will be conducted to validate the utility of EEG biomarkers as an aid to antidepressant treatment selection in adults with MDD.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Sertraline; Drug: Escitalopram

Detailed Description

The LEAP-SE study is an 8-week, multicenter, randomized, blinded study to evaluate the performance of EEG-based biomarkers in predicting treatment outcome. Study participants will be randomized in a 1:1 ratio to receive either sertraline or escitalopram and followed for 8 weeks.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged 22 or older at the time of informed consent.
• Diagnosis of Major Depressive Disorder (MDD) based on the Structured Clinical Interview for DSM-5 for depression.
• Moderate or severe depression on DSM-5 depression criteria items, as assessed by a score of 10 or more on the Patient Health Questionnaire (PHQ-9)
• Has not taken either study medications (sertraline, escitalopram) in the current episode
• Has not received electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or esketamine treatment in the current episode
• Provision of personally signed and dated written informed consent prior to any study procedures
• Agrees to, and is eligible for all biomarker assessments (EEG, neurocognitive testing, activity and sleep monitoring, genetic testing)
• Fluent in English
• Ability to complete all assessments independently
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• Diagnosis of bipolar disorder or a psychotic disorder based on the Structured Clinical Interview for DSM-5.
• Concurrent use of antidepressants, antipsychotics or mood stabilizers
• Use of hypnotics, anxiolytics or opiate pain medications greater than three days per week and unable to reduce use to three or fewer days per week on an as needed basis
• Pregnant or breastfeeding
• Severe impediment to vision, hearing, comprehension, and/or hand movement that interferes with study tasks
• Active substance use that interferes with ability to consent and/or complete assessments
• Any contraindication to EEG (e.g. requiring high concentration oxygen)
• Employees/family of employees of clinic site
• Participation in another research study within 2 months prior to the first study visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sertraline; Sertraline 100-200 mg daily for 8 weeks	Drug: Sertraline; FDA approved antidepressant; Other Names: Zoloft
ACTIVE_COMPARATOR: Escitalopram; Escitalopram 10-20 mg daily for 8 weeks	Drug: Escitalopram; FDA approved antidepressant; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate on the 16-item patient-reported Quick Inventory of Depressive Symptoms (QIDS-SR) at the week 8 endpoint as a function of biomarker score	Response rate will be calculated as the percentage of participants meeting response criteria (>50% reduction from baseline QIDS-SR total score at 8-week endpoint). The QIDS-SR is a 16-item, participant-rated short form of the Inventory of Depressive Symptomatology that assesses 9 domains: sad mood, concentration, self-outlook, suicidal ideation, involvement, energy/fatigability, sleep disturbance, appetite/weight increase/decrease and psychomotor agitation/retardation. Scores range from 0 (none) to 27 (very severe). The QIDS-SR total score was used to derive the mean change from baseline to endpoint depression.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute score decrease from baseline to the week 8 endpoint on the QIDS-SR as a function of biomarker score	Quick Inventory of Depressive Symptoms (QIDS-SR)	8 weeks
Percentage decrease in depressive symptoms on the patient-reported Quick Inventory of Depressive Symptoms (QIDS-SR) at the week 8 endpoint as a function of biomarker score	Quick Inventory of Depressive Symptoms (QIDS-SR)	8 weeks

Collaborators and Investigators

• Sponsor: Alto Neuroscience
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 15, 2020
• Primary Completion (ANTICIPATED): May 30, 2023
• Study Completion (ANTICIPATED): May 30, 2023

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (ACTUAL): May 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 13, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Biomarker; EEG; Major Depressive Disorder; Sertraline; Antidepressant; Escitalopram
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Sertraline; Citalopram
• Other Study ID Numbers: LEAP-SE; 1R44MH123373-01 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes