Optimization of IV Ketamine for Treatment Resistant Depression

• ClinicalTrials.gov Identifier: NCT00768430
• Recruitment Status: Completed
• First Posted: October 8, 2008
• Results First Posted: January 31, 2014
• Last Update Posted: January 31, 2014
• Sponsor: Baylor College of Medicine
• Collaborator: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Sanjay Johan Mathew, Baylor College of Medicine

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Major Depressive Disorder (MDD); Treatment Resistant Depression (TRD)
• Interventions: Drug: Ketamine; Drug: Midazolam
• Enrollment: 73

Participant Flow

Recruitment Details	The study enrolled patients at two academic sites, Baylor College of Medicine and Icahn School of Medicine at Mount Sinai, between November 2010 and August 2012.
Pre-assignment Details	The protocol required patients to be drug free prior to the infusion, for at at least 1 week (4 for fluoxetine) for those taking other medications. Randomly assigned in a 2:1 ratio, the patients received a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) or midazolam (0.045 mg/kg) infused over 40 minutes.

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description	single infusion of 0.5mg/kg of Ketamine HCL	single infusion of midazolam being used as an active control for the study
Period Title: 24 Hour Endpoint
Started	48	25
Completed	47	25
Not Completed	1	0
Period Title: 7 Day Endpoint
Started	47	25
Completed	45	22
Not Completed	2	3
Reason Not Completed
Withdrawal by Subject	2	3

Baseline Characteristics

Arm/Group Title		Ketamine	Midazolam	Total
Arm/Group Description		Ketamine	Midazolam	Total of all reporting groups
Overall Number of Baseline Participants		48	25	73
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	48 participants	25 participants	73 participants
		46.9 (12.8)	42.7 (11.6)	44.8 (12.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	48 participants	25 participants	73 participants
	Female	27 56.3%	11 44.0%	38 52.1%
	Male	21 43.8%	14 56.0%	35 47.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	48 participants	25 participants	73 participants
		48	25	73

Outcome Measures

1. Primary Outcome

Title	MADRS
Description	Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression.
Time Frame	24 hours post-infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Ketamine	Midazolam
Overall Number of Participants Analyzed	47	25
Mean (95% Confidence Interval); Unit of Measure: units on a scale
	14.77; (11.73 to 17.80)	22.72; (18.85 to 26.59)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ketamine		Midazolam
Arm/Group Description	Ketamine		Midazolam
All-Cause Mortality
	Ketamine		Midazolam
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Ketamine		Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/47 (4.26%)		0/25 (0.00%)
Cardiac disorders
Hypotension/Bradycardia * [1]	1/47 (2.13%)	1	0/25 (0.00%)	0
Social circumstances
Suicide Attempt * [2]	1/47 (2.13%)	1	0/25 (0.00%)	0
* Indicates events were collected by non-systematic assessment; [1] Hypotension (BP=73/40 for 1 min)/bradycardia (HR <30 bpm for 30 sec, followed by spontaneous recovery). This occurred while the subject was undergoing venipuncture at the 30 min time point and was considered a vaso- vagal episode.; [2] Suicide Attempt: While tapering off of psychotropic medication, patient was hospitalized following an attempted overdose.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ketamine		Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/47 (100.00%)		25/25 (100.00%)
Gastrointestinal disorders
Nausea †	16/47 (34.04%)		3/25 (12.00%)
Dry Mouth †	12/47 (25.53%)		4/25 (16.00%)
Nervous system disorders
Headache †	15/47 (31.91%)		5/25 (20.00%)
Dizziness on standing †	10/47 (21.28%)		2/25 (8.00%)
Poor Concentration †	19/47 (40.43%)		12/25 (48.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

Limitations of our trial include stringent enrollment criteria due to concerns about ketamine's psychoactive effects and abuse liability. A proportion of screened patients (17.2%) refused or were unable to tolerate psychotropic washout.

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.

Results Point of Contact

• Name/Title: Dr. Sanjay Mathew
• Organization: Baylor College of Medicine
• Phone: 7137911414 ext 5439
• EMail: sjmathew@bcm.edu

Publications:

Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.

Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.

• Responsible Party: Sanjay Johan Mathew, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT00768430
• Other Study ID Numbers: GCO 07-0114
• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Results First Submitted: September 5, 2013
• Results First Posted: January 31, 2014
• Last Update Posted: January 31, 2014