Study of Neural Responses Induced by Antidepressant Effects (SONRISA)

Study of Neural Responses Induced by Simulated Antidepressants

The proposed work aims to examine the neural changes associated with fast-acting antidepressant treatments in order to develop imaging-based biomarkers of treatment response for depression.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Escitalopram; Behavioral: Real-time Neurofeedback fMRI task pre- and post-RCT

Detailed Description

Over the past decade, neuroimaging tools have rapidly advanced the field of neural biomarkers of treatment response in depression. Still, despite obvious scientific progress in this field, the ability to implement neuroimaging biomarkers of antidepressant treatment response in clinical trial settings is lacking. In order to objectively assess the neural bases of treatment response in depression, the investigators will use a "Real-time Neurofeedback fMRI task", specifically designed to record and modulate mood improvement by providing neurofeedback in the context of the administration of an antidepressant treatment. In a pilot study, positive neurofeedback during the administration of the drug was associated with significant acute mood improvement and increased blood oxygen level dependent (BOLD) responses in the rostral anterior cingulate cortex (rACC), a common neural target of antidepressant treatments. The central hypothesis is that antidepressant effects in depression are mediated by increased neural activity in the rACC (AIM1), which can be used in clinical trials of antidepressant treatment to predict antidepressant effects (AIM 2) and assess the effect of antidepressant treatment on antidepressant-induced rACC neural responses (AIM 3). The results obtained from this project are expected to have an important impact on our ability to understand the cognitive and neural mechanisms implicated in antidepressant treatment responses in patients with depression, as well as on the ability to implement neuroimaging biomarkers of treatment response in the clinical trial settings.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • WPIC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A man or woman age of 18 or older.
• Currently experiencing a depressive episode as part of Major Depressive Disorder.
• Able to tolerate lying still on your back for 60 minutes at a time.
• Have had no more than one failed antidepressant trial of adequate dose and duration.
• Have been antidepressant medication-free for at least 21 days prior to collection of imaging data (5 weeks for fluoxetine)

Exclusion Criteria:

• Are currently taking any psychiatric medication, or any potentially augmenting or sedative drugs.
• Have a history of inadequate response/tolerability to escitalopram; or history of resistant depression
• Pregnant or breastfeeding or plan to become pregnant over the duration of the study.
• Have a history (lifetime) of psychotic depressive, schizophrenic, bipolar, schizoaffective, or other Axis I psychotic disorders.
• Meet criteria for substance dependence in the last 6 months, except nicotine, or substance abuse in the last 2 months.
• Have a medical condition that contradicts treatment with escitalopram.
• Are currently receiving psychotherapy or any other treatment for your depression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Antidepressant Treatment; 20mg of escitalopram will be taken over an 8-week period, starting with 10mg for the first week.	Drug: Escitalopram; Selective Serotonin Reuptake Inhibitor (SSRI); Other Names: Lexapro; Behavioral: Real-time Neurofeedback fMRI task pre- and post-RCT; Placebo experiment during an fMRI scanning session
Placebo Comparator: Placebo; A placebo pill will be taken over an 8-week period.	Drug: Placebo; Placebo; Behavioral: Real-time Neurofeedback fMRI task pre- and post-RCT; Placebo experiment during an fMRI scanning session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Scores	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. It was designed in 1979 by British and Swedish researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale was.[2] There is, however, a high degree of statistical correlation between scores on the two measures.	baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quick Inventory of Depressive Symptomatology (QIDS) Scores	The Quick Inventory of Depressive Symptomatology (QIDS) is a 16-item, self-reported measure of depression that ranges from 1 (no depression) to 27 (very severe depression).	baseline and 8 weeks
Neural Responses During the Sham Neurofeedback fMRI Task.	Voxel-wise BOLD changes during the expectancy condition of the Sham Neurofeedback fMRI task.	Baseline

Collaborators and Investigators

• Sponsor: Marta Peciña, MD PhD

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 4, 2016

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Depression; MDD; Neurofeedback; Neuroimaging biomarkers
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; 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; Citalopram
• Other Study ID Numbers: STUDY19070392/PRO16050131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The study will follow NIMH schedule for data sharing for clinical trials. The schedule allows for descriptive data to be submitted - but not shared - ongoing and results associated with a finding - both positive and negative - to be submitted prior to the communication of a result. Once a result is communicated, either through publication and/or on the NDCT website the data specifically defined to the clinical trial will then be shared.