Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder (PTSD) (KetPTSD)

• ClinicalTrials.gov Identifier: NCT00749203
• Recruitment Status: Completed
• First Posted: September 9, 2008
• Results First Posted: February 14, 2018
• Last Update Posted: February 14, 2018
• Sponsor: Dennis Charney
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Dennis Charney, Icahn School of Medicine at Mount Sinai

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Stress Disorders, Post-Traumatic; PTSD; Depression; Anxiety Disorder
• Interventions: Drug: Midazolam; Drug: Ketamine
• Enrollment: 41

Participant Flow

Recruitment Details	Patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements beginning Jan 2009, and were enrolled at the Icahn School of Medicine at Mount Sinai, New York, between May 2009 and December 2012.
Pre-assignment Details

Arm/Group Title	Ketamine Then Midazolam	Midazolam Then Ketamine
Arm/Group Description	Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes on day 1, then 2 weeks later, Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes	Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes on day 1, then 2 weeks later, Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes
Period Title: First Infusion Day 1
Started	22	19
Completed	22	19
Not Completed	0	0
Period Title: no Infusion at Week 1
Started	22	19
Completed	22	15
Not Completed	0	4
Reason Not Completed
Lost to Follow-up	0	1
Withdrawal by Subject	0	1
delayed-onset sedation	0	1
low baseline PTSD symptoms level	0	1
Period Title: Second Infusion at 2 Weeks
Started	16 [1]	15
Completed	16	13
Not Completed	0	2
Reason Not Completed
Protocol Violation	0	1
pt felt uncomfortable after infusion	0	1
[1] N=6 completed the study at 2 wks due to CAPS scores < 50, precluding 2nd infusion.

Baseline Characteristics

Arm/Group Title		Ketamine Then Midazolam	Midazolam the Ketamine	Total
Arm/Group Description		Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes on Day 1, then 2 weeks later, Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes	Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes on Day 1, then 2 weeks later Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	Total of all reporting groups
Overall Number of Baseline Participants		22	19	41
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants	19 participants	41 participants
		36.4 (10.8)	35.7 (10.0)	36.05 (10.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	19 participants	41 participants
	Female	13 59.1%	6 31.6%	19 46.3%
	Male	9 40.9%	13 68.4%	22 53.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	19 participants	41 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	11 50.0%	12 63.2%	23 56.1%
	White	5 22.7%	2 10.5%	7 17.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	6 27.3%	5 26.3%	11 26.8%
Education; Measure Type: Number; Unit of measure: Participants	Number Analyzed	22 participants	19 participants	41 participants
less than high school		1	0	1
high school graduate		3	3	6
some college		12	14	26
more than 4 years of college		5	2	7
unknown		1	0	1
Percentage Unemployed; Measure Type: Number; Unit of measure: Percentage of participants
	Number Analyzed	22 participants	19 participants	41 participants
		50	73.7	123.7
Primary Trauma; Measure Type: Number; Unit of measure: Participants	Number Analyzed	22 participants	19 participants	41 participants
Sexual assault or molestation		9	0	9
Physical assault or abuse		4	7	11
Accident or fire		1	3	4
Combat exposure		2	0	2
Witnessed violent assault or death		4	5	9
Witnessed 9/11 terrorist attacks		2	0	2
Unknown		0	4	4
Duration of PTSD; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants	19 participants	41 participants
		14.2 (12.3)	11.9 (14.0)	13.1 (13.1)
History of treatment with psychotropic medication; Measure Type: Number; Unit of measure: Percentage of participants
	Number Analyzed	22 participants	19 participants	41 participants
		50	42.1	92.1
Clinician-Administered PTSD Scale (CAPS) score (past month) [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	22 participants	19 participants	41 participants
		82.5 (14.1)	77.1 (11.8)	80.0 (13.0)
		[1] Measure Description: frequency score - scale 0 = none of the time to 4 = most or all of the time intensity score - scale 0 = none to 4 = extreme To meet criteria for a symptom, a patient must meet criteria in both frequency and intensity score for each item. Frequency and intensity and then combined to form a single severity score. 30 questions scale, with total score ranging from 0 to 240.
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	22 participants	19 participants	41 participants
		12.4 (5.2)	11.3 (5.6)	11.9 (5.4)
		[1] Measure Description: Each item is rated 0 (no depression) to 3 (severe depression). The total score ranges from 0-27.

Outcome Measures

1. Primary Outcome

Title	Impact of Event Scale - Revised (IES-R)
Description	A 22-item self-report questionnaire measuring PTSD symptoms. Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score ranging from 0 (not at all) to 88 (extremely)
Time Frame	7 days after first infusion

Outcome Measure Data

Analysis Population Description

Not all participants returned for the 1 week follow up visit. There were 19 participants from the Ketamine group and 15 participants from the Midazolam group who returned for their followup visit and completed the IES-R at the 1 week follow up visit.

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	single dose 0.045 mg/kg IV infused over 40 minutes Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
Overall Number of Participants Analyzed	19	15
Mean (Standard Deviation); Unit of Measure: units on a scale
	25.76 (19.4)	36.32 (13.73)

2. Secondary Outcome

Title	Clinician-Administered PTSD Scale (CAPS)
Description	Clinician-administered structured interview measuring PTSD symptoms. frequency score - scale 0 = none of the time to 4 = most or all of the time intensity score - scale 0 = none to 4 = extreme To meet criteria for a symptom, a patient must meet criteria in both frequency and intensity score for each item. Frequency and intensity and then combined to form a single severity score. 30 questions scale, with total score ranging from 0 to 240.
Time Frame	7 days after first infusion

Outcome Measure Data

Analysis Population Description

Not all participants returned for the 1 week follow up visit. There were 19 participants from the Ketamine group and 15 participants from the Midazolam group who returned for their followup visit and completed the IES-R at the 1 week follow up visit.

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	single dose 0.045 mg/kg IV infused over 40 minutes Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
Overall Number of Participants Analyzed	19	15
Mean (Standard Deviation); Unit of Measure: units on a scale
	54 (23.63)	65.69 (16.36)

3. Secondary Outcome

Title	Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
Description	Self-report questionnaire measuring depressive symptoms. Each item is rated 0 (no depression) to 3 (severe depression). The total score ranges from 0-27.
Time Frame	24 hours after first infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	single dose 0.045 mg/kg IV infused over 40 minutes Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
Overall Number of Participants Analyzed	22	19
Mean (Standard Deviation); Unit of Measure: units on a scale
	12.4 (5.2)	11.3 (5.6)

4. Secondary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Clinician-administered questionnaire measuring depressive symptoms. The MADRS-S has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Mean difference between baseline and 2 weeks.
Time Frame	24 hours after first infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	single dose 0.045 mg/kg IV infused over 40 minutes Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
Overall Number of Participants Analyzed	22	19
Mean (Standard Deviation); Unit of Measure: units on a scale
	12.6 (7.9)	10.1 (9.7)

5. Secondary Outcome

Title	Hopkins Verbal Learning Test (HVLT)
Description	Repeatable test of memory acquisition and delayed recall of words. It is a three-trial list learning and free recall task comprising 12 words, 4 words from each of three semantic categories. Total Recall score range is 0 to 36.
Time Frame	20 to 40 minutes after infusion

Outcome Measure Data

Analysis Population Description

data not collected

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description:	Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes	single dose 0.045 mg/kg IV infused over 40 minutes Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	24 hours post infusion
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Ketamine	Midazolam
Arm/Group Description	Ketamine: Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes,	Midazolam: single dose 0.045 mg/kg IV infused over 40 minutes
All-Cause Mortality
	Ketamine	Midazolam
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/38 (0.00%)	0/31 (0.00%)
Serious Adverse Events
	Ketamine	Midazolam
	Affected / at Risk (%)	Affected / at Risk (%)
Total	33/38 (86.84%)	31/31 (100.00%)
Cardiac disorders
Palpitation † 1	3/38 (7.89%)	0/31 (0.00%)
Dizziness on standing † 1	6/38 (15.79%)	5/31 (16.13%)
Chest Pain † 1	2/38 (5.26%)	3/31 (9.68%)
Ear and labyrinth disorders
Ringing in ears † 1	5/38 (13.16%)	1/31 (3.23%)
Eye disorders
Blurred vision † 1	15/38 (39.47%)	6/31 (19.35%)
Gastrointestinal disorders
Diarrhea † 1	3/38 (7.89%)	2/31 (6.45%)
Dry Mouth † 1	10/38 (26.32%)	4/31 (12.90%)
Nausea/Vomiting † 1	10/38 (26.32%)	0/31 (0.00%)
General disorders
Difficulty sleeping † 1	3/38 (7.89%)	3/31 (9.68%)
Sleeping too much † 1	2/38 (5.26%)	1/31 (3.23%)
Anxiety † 1	5/38 (13.16%)	1/31 (3.23%)
Poor concentration † 1	4/38 (10.53%)	6/31 (19.35%)
General malaise † 1	3/38 (7.89%)	1/31 (3.23%)
Restlessness † 1	13/38 (34.21%)	4/31 (12.90%)
Fatigue † 1	10/38 (26.32%)	6/31 (19.35%)
Decreased energy † 1	6/38 (15.79%)	3/31 (9.68%)
Nervous system disorders
Headace † 1	8/38 (21.05%)	4/31 (12.90%)
Tremors † 1	0/38 (0.00%)	1/31 (3.23%)
Poor coordination † 1	7/38 (18.42%)	1/31 (3.23%)
Dizziness † 1	14/38 (36.84%)	9/31 (29.03%)
Renal and urinary disorders
Difficulty urinating † 1	0/38 (0.00%)	3/31 (9.68%)
Painful urination † 1	2/38 (5.26%)	1/31 (3.23%)
Frequent urination † 1	2/38 (5.26%)	4/31 (12.90%)
Skin and subcutaneous tissue disorders
Rash † 1	1/38 (2.63%)	0/31 (0.00%)
Increased perspiration † 1	3/38 (7.89%)	1/31 (3.23%)
Itching † 1	1/38 (2.63%)	0/31 (0.00%)
Dry skin † 1	2/38 (5.26%)	1/31 (3.23%)
1 Term from vocabulary, PRISE; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Ketamine	Midazolam
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/38 (0.00%)	0/31 (0.00%)

Limitations and Caveats

Several patients did not receive a second infusion per protocol because of sustained reduction in PTSD symptom levels . The study also does not address the safety or efficacy of ketamine in combination with other psychotropic medications in PTSD.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Adriana Feder
• Organization: Icahn School of Medicine at Mount Sinai
• Phone: 212-241-1563
• EMail: adriana.feder@mssm.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):

Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

• Responsible Party: Dennis Charney, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT00749203
• Other Study ID Numbers: GCO 07-1199; PT074949; IF1554104; A-15236 ( Other Identifier: USAMRMC ORP HRPO )
• First Submitted: September 5, 2008
• First Posted: September 9, 2008
• Results First Submitted: April 12, 2017
• Results First Posted: February 14, 2018
• Last Update Posted: February 14, 2018