Ketamine for Depression: An MRI Study

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02544607
• Collaborator: Brain & Behavior Research Foundation (Other), National Institutes of Health (NIH) (NIH)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 21.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depression; Anxious Depression; Major Depressive Disorder	Drug: Ketamine; Other: Magnetic Resonance Imaging (MRI)	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Baseline Insular Dysfunction as a Predictor of Ketamine's Antidepressant Effects in Anxious Depression
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Dec 29, 2017
• Actual Study Completion Date: Dec 29, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion. [4 hours]

   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.

Secondary Outcome Measures

1. Percent Change in Tissue Fractional Anisotropy Quantification (Left Inferior Longitudinal Fasciculus) [4 hours]

   Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion

2. Percent Change in Tissue Fractional Anisotropy Quantification (Right Inferior Longitudinal Fasciculus) [4 hours]

   Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion

3. Percent Change in Tissue Fractional Anisotropy Quantification (Left Superior Longitudinal Fasciculus) [4 hours]

   Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion

4. Percent Change in Tissue Fractional Anisotropy Quantification (Right Uncinate Fasciculus) [4 hours]

   Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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,
2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Brain & Behavior Research Foundation
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Cristina Cusin, M.D., MGH

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 9, 2017

More Information

Additional Information:

• MGH Depression Clinical and Research Program

Publications

None provided.

• Responsible Party: Cristina Cusin, MD, Cristina Cusin, M.D., Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02544607
• Other Study ID Numbers: 2015P001912; 24032
• First Posted: Sep 9, 2015
• Last Update Posted: Apr 16, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cristina Cusin, MD, Cristina Cusin, M.D., Massachusetts General Hospital: Ketamine; Depression; Anxious Depression; MRI
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Ketamine

Study Results

Participant Flow

Recruitment Details	As specified, the total number of participants enrolled are those who agreed to participate in the study following completion of the informed consent process (n=25). This number does not reflect the number of subjects who actually started treatment (n=16).

Arm/Group Title	Ketamine + MRI
Arm/Group Description	All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging Ketamine: Ketamine 0.5mg/kg over 40 minutes IV
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ketamine
Arm/Group Description	All eligible participants will receive open label ketamine Ketamine: Ketamine 0.5mg/kg over 40 minutes IV
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (14)
Sex: Female, Male (Count of Participants)
Female	8 50%
Male	8 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.3%
Not Hispanic or Latino	15 93.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 6.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	14 87.5%
More than one race	0 0%
Unknown or Not Reported	1 6.3%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion.
Description	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.
Time Frame	4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine
Arm/Group Description	All eligible participants will receive open label ketamine Ketamine: Ketamine 0.5mg/kg over 40 minutes IV
Measure Participants	16
Mean (Full Range) [score on a scale]	-9.625

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.

Arm/Group Title	Ketamine + MRI
Arm/Group Description	All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI). Ketamine: Ketamine 0.5mg/kg over 40 minutes IV Magnetic Resonance Imaging (MRI): MRI technology will be used before and after ketamine for patients with depression
Measure Participants	13
Number [percent change]	.901

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.

Arm/Group Title	Ketamine + MRI
Arm/Group Description	All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI). Ketamine: Ketamine 0.5mg/kg over 40 minutes IV Magnetic Resonance Imaging (MRI): MRI technology will be used before and after ketamine for patients with depression
Measure Participants	13
Number [percent change]	1.247

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.

Arm/Group Title	Ketamine + MRI
Arm/Group Description	All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI). Ketamine: Ketamine 0.5mg/kg over 40 minutes IV Magnetic Resonance Imaging (MRI): MRI technology will be used before and after ketamine for patients with depression
Measure Participants	13
Number [percent change]	.696

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.0499
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.

Arm/Group Title	Ketamine + MRI
Arm/Group Description	All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI). Ketamine: Ketamine 0.5mg/kg over 40 minutes IV Magnetic Resonance Imaging (MRI): MRI technology will be used before and after ketamine for patients with depression
Measure Participants	13
Number [percent change]	1.158

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ketamine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse event data were collected throughout the course of the study. The collection of this data took place at the initial screen, continuously throughout the duration of the administration visit (e.g. Visit 2), 24 hours post-administration, and up to 3 months following the administration visit.
Arm/Group Title	Ketamine
Arm/Group Description	All eligible participants will receive open label ketamine Ketamine: Ketamine 0.5mg/kg over 40 minutes IV
All Cause Mortality
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Serious Adverse Events
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine
	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)
Eye disorders
bilateral nystagmus	1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.