Ketamine for Depression: An MRI Study

Baseline Insular Dysfunction as a Predictor of Ketamine's Antidepressant Effects in Anxious Depression

Ketamine has been shown to decrease symptoms of anxious depression quickly. This decrease has been shown to last for up to one month. MRI technology will be used before and after ketamine for patients with depression to examine the extent to which certain brain areas predict ketamine's antidepressant effects.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depressive Disorder; Anxious Depression
• Intervention / Treatment: Drug: Ketamine; Other: Magnetic Resonance Imaging (MRI)

Detailed Description

Ketamine's antidepressant effects were measured with Hamilton Depression Rating Scale (HDRS). MRI data will also be analyzed to examine the extent to which certain brain areas predict ketamine's antidepressant effects.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria: Patients with Depression

Patients will:

1. be 18-64 years old,
2. read, understand, and provide written informed consent in English,
3. meet criteria for a primary psychiatric diagnosis of major depressive disorder for ≥ 4 weeks,
4. have a history of ≥1 failed medication trial during the current depression
5. be on a stable antidepressant and psychotherapy regimen for ≥28 days,
6. maintain a treating doctor who is in agreement with study participation,
7. have a reliable chaperone accompany them home following the completion of the ketamine infusion day,
8. be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG),
9. be of non-childbearing potential or use of an acceptable form of birth control (females only),
10. be right handed.

Exclusion Criteria: Patients with Depression

Patients will be excluded if any of the following criteria are met:

1) delirium or dementia diagnosis, 2) unstable medical illness or clinically significant laboratory results, 3) history of clinically significant cardiovascular disease or electrocardiogram (EKG) findings, or medical conditions that put the patient at risk for possible cardiac side effects or alter brain morphology (e.g., traumatic brain injury), 4) history of multiple adverse drug reactions, 5) current/past history of psychotic disorders, 6) active substance use disorders (except nicotine and caffeine) within the past six months or past history of ketamine/PCP abuse, 7) requirement of excluded medications that may interact with ketamine, 8) weigh >250 lbs., 9) pregnancy, breastfeeding, or unacceptable means of birth control (females only) 10) presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)), 11) current serious suicidal or homicidal risk, or 12) concurrent participation in other research studies.

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Inclusion Criteria: Healthy Controls

Healthy Controls will:

1. be 18-64 years old,
2. read, understand, and provide written informed consent in English,
3. have a reliable chaperone accompany them home following the completion of the ketamine infusion day,
4. be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG),
5. be of non-childbearing potential or use of an acceptable form of birth control (females only), and
6. be right handed.

Exclusion Criteria: Healthy Controls

Healthy controls will be excluded if any of the following criteria are met:

1. current or past psychiatric diagnosis (excluding phobias), including alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine),
2. presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)),
3. presence of medical illness likely to alter brain morphology and/or physiology (e.g., traumatic brain injury),
4. requirement of excluded medications that may interact with ketamine,
5. presence of psychiatric disorders in first-degree relatives,
6. pregnancy, breastfeeding, or unacceptable means of birth control (females only), or
7. weight >250 lbs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine + MRI; All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI).	Drug: Ketamine; Ketamine 0.5mg/kg over 40 minutes IV; Other Names: Ketamine Hydrochloride; Other: Magnetic Resonance Imaging (MRI); MRI technology will be used before and after ketamine for patients with depression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion.	Hamilton Depression Rating Scale; possible scores range from 0 to 81 with higher scores indicating higher depression symptoms Change will be calculated by difference between HDRS from Minute 0 to Minute 240.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Tissue Fractional Anisotropy Quantification (Left Inferior Longitudinal Fasciculus)	Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion	4 hours
Percent Change in Tissue Fractional Anisotropy Quantification (Right Inferior Longitudinal Fasciculus)	Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion	4 hours
Percent Change in Tissue Fractional Anisotropy Quantification (Left Superior Longitudinal Fasciculus)	Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion	4 hours
Percent Change in Tissue Fractional Anisotropy Quantification (Right Uncinate Fasciculus)	Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion	4 hours

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institutes of Health (NIH); Brain & Behavior Research Foundation
• Investigators: Principal Investigator: Cristina Cusin, M.D., MGH

Publications and helpful links

Helpful Links

• MGH Depression Clinical and Research Program

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): December 29, 2017
• Study Completion (Actual): December 29, 2017

Study Registration Dates

• First Submitted: September 4, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimate): September 9, 2015

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: MRI; Depression; Ketamine; Anxious Depression
• 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; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2015P001912; 24032 (Other Grant/Funding Number: 2015 NARSAD Young Investigator Grant)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No