MRI Studies of Emotion in Depression

• ClinicalTrials.gov Identifier: NCT02429011
• Recruitment Status: Completed
• First Posted: April 29, 2015
• Last Update Posted: April 6, 2017
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): James Murrough, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: April 24, 2015
• First Posted Date: April 29, 2015
• Last Update Posted Date: April 6, 2017
• Actual Study Start Date: July 15, 2011
• Actual Primary Completion Date: May 31, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2015)

Change in Montgomery-Asberg Depression Rating Scale [ Time Frame: baseline and 24hrs post fMRI scan ]

The Montgomery-Asberg Depression Rating Scale (74) is a well-validated 10-item instrument with good ecological validity. It is used extensively in clinical research for the evaluation of depressive symptoms in adults, and is particularly sensitive to detecting change in symptoms. This scale serves as the primary depression-related behavioral rating for correlation with our neuroimaging data.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 28, 2015)

• Change in Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) [ Time Frame: baseline and 24hrs post fMRI scan ]
  The 30-item Clinician-Rated Inventory of Depressive Symptomatology (IDS-C30) (75) is a clinician-rated instrument which includes all DSM-IV diagnostic criterion items for MDD as well as commonly associated symptoms such as anxiety, irritability, and melancholic and atypical symptom features.
• Change in Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: baseline and 24hrs post fMRI scan ]
  Potential dissociative or other acute behavioral changes during the KET/MID infusions will be assessed using the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale (CADSS)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MRI Studies of Emotion in Depression
• Official Title: Functional MRI Studies of Emotion in Depression and Rapid Antidepressant Response

Brief Summary

The purpose of this study is to research the effects of ketamine on brain function in patients with Major Depressive Disorder (MDD). This study is an ancillary MRI neuroimaging study being conducted in patients with MDD who are enrolled in a separate clinical trial. Healthy control volunteers are also enrolled. No drug or other intervention is given as part of this protocol per se.

To study brain activity related to emotion, the study team will use a technology called functional MRI (fMRI), which is a method for evaluating the flow of blood in the brain using a powerful magnet. fMRI does not involve exposure to radiation.

Patients will be shown a sample of images on a computer screen designed to bring about an emotional reaction. The MRI machine will then take a number of pictures of your head. By computer analysis, this machine is able to create a picture of your brain's activity. There are several tasks during scanning that involve looking at various images that represent different emotions, and the study team will be monitoring brain activity during these tasks.

Patients will be scanned before and 24 hours after receiving ketamine (as part of a separate study) to analyze treatments effects. These scans are compared to depressed patients who did not receive ketamine, as well as to healthy controls.

Detailed Description

Specific Aim 1: To characterize the function of basic neural systems involved in emotion perception and regulation in TRD.

• Experiment 1.1: Neural responses to emotional faces in TRD (neutral, low and high intensity sad facial expressions).

  o Hypothesis 1.1: Patients with TRD, relative to HC participants, will evidence increased activation in the amygdala/parahippocampal gyrus to sad compared to neutral faces.

• Experiment 1.2: Neural responses during negative emotion regulation in TRD (cognitive reappraisal).

  • Hypothesis 1.2: Patients with TRD, relative to HC participants, will show enhanced activation of the amygdala during the generation of negative affect and will be impaired in their ability to recruit PFC/ACC regions during attempts to down-regulate negative affect.

Specific Aim 2: To characterize changes in emotion-processing neural networks associated with ketamine and rapid antidepressant response.

• Experiment 2.1: Neural changes in response to emotional faces associated with ketamine and rapid antidepressant response.

  o Hypothesis 2.1a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala to sad compared to neutral faces. 2.1b: Antidepressant response, compared to non-response, will be specifically associated with changes in PFC/ACC function.

• Experiment 2.2: Neural changes during negative emotion regulation (cognitive reappraisal) associated with ketamine and rapid antidepressant response.

  • Hypothesis 2.2a: Ketamine, compared to midazolam, will be associated with reduced activation in the amygdala during negative emotion generation and enhanced PFC/ACC function during down-regulation of negative affect. 2.2b: Antidepressant response, compared to non-response, will be specifically associated with enhancement of PFC/ACC function.

Specific Aim 3 (Exploratory): To investigate functional and effective connectivity between emotion perception/generation neural systems and cognitive emotional regulation systems. Hypothesis 3: TRD compared to HC will be characterized by abnormal connectivity between PFC/ACC and amygdala, which will normalize with rapid antidepressant response.

The setting of research will be MSSM. All research participants will be recruited and screened through the Mood and Anxiety Disorders Program (MAP) (Director: Dan V. Iosifescu, M.D.) at MSSM. MAP is one of the major clinical research programs of the Department of Psychiatry, with research funding from NIH, the Department of Defense, NARSAD, and industry.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample

Study Population

The research plan calls for the recruitment of adult human subjects with major depressive disorder (MDD) or healthy control (HC) volunteers over the 5-year grant period. All participants are required to be medically healthy as determined by medical history, physical examination, ECG, screening blood laboratory tests, urine analysis, and urine toxicology drug screen. Participants with MDD must have demonstrated inadequate therapeutic response to a minimum of one adequate antidepressant trial (e.g. TRD). MDD participants who meet this minimum TRD threshold will be eligible for the experiments in Aim 1.

We recruit participants from several Mount Sinai-affiliated community hospitals (North General Hospital, Elmhurst), mental health associations (National Alliance for the Mentally Ill, Mood Disorders Support Group of New York), the Mood and Anxiety Disorders Program (MAP) Outpatient Clinic, the Mount Sinai Hospital outpatient psychiatry clinic, and from media/internet advertising.

• Condition: Major Depressive Disorder
• Intervention: Not Provided

Study Groups/Cohorts

• MDD
  patients with current MDD
• Healthy Control (HC)
  healthy control volunteers

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 21, 2016): 135
• Original Estimated Enrollment (submitted: April 28, 2015): 112
• Actual Study Completion Date: May 31, 2016
• Actual Primary Completion Date: May 31, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female participants, 18-70 years of age;
• Participants must be free of any psychiatric condition (for the healthy volunteer group) or meet DSM-IV criteria for major depressive disorder, without psychotic features, based on the Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID);
• Participants have demonstrated inadequate response to a minimum of 1 adequate antidepressant treatment trial in current episode (e.g. TRD);
• Participants must be willing to undergo washout of psychotropic medications that he or she is taking;
• Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Exclusion Criteria:

• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation;
• Current diagnosis of obsessive-compulsive disorder (OCD), but not other anxiety disorders;
• Diagnosis of a substance use disorder within the past six months; all participants must have a negative urine toxicology test on the day of the fMRI, prior to the scan;
• Female participants who are pregnant, nursing, for may become pregnant;
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
• Clinically significant abnormalities of laboratories, physical examination, or ECG;
• Participants judged to be at serious suicidal risk by the PI or another study-affiliated psychiatrist;
• Any contraindications to MRI, including pacemakers or metallic objects in the body.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02429011
• Other Study ID Numbers: GCO 10-1385; 5K23MH094707 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: James Murrough, Icahn School of Medicine at Mount Sinai
• Study Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: James Murrough, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: April 2017