Ketamine as a Treatment for Post-Traumatic Stress Disorder (PTSD)

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT02397889
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 56.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to study new ways to treat post-traumatic stress disorder (PTSD). Current treatments for PTSD do not work for everyone and it can take time to determine whether a person responds to a chosen treatment. The purpose of this study is to see whether ketamine, when given repeatedly intravenously can produce a quick and persistent improvement in PTSD symptoms. At higher doses, ketamine has been used for many years as an anesthetic for medical procedures, and at lower doses may be an effective treatment in patients with major depression and PTSD. Ketamine given for PTSD is investigational, which means that the FDA has not yet approved the drug for treating this condition. In this study, the effects of ketamine will be compared to those of midazolam. Midazolam has similar acute anesthetic effects compared to ketamine but has not been shown to treat or alleviate any symptoms of PTSD. This makes midazolam an appropriate substance to gauge whether ketamine can treat or alleviate PTSD symptoms thereby acting as what we call an active control.

Condition or Disease	Intervention/Treatment	Phase
Posttraumatic Stress Disorder (PTSD)	Drug: Ketamine; Drug: Midazolam	Phase 2/Phase 3

Detailed Description

Ketamine is an approved medication in several countries for the induction of general anesthesia and for use as adjunct to other anesthetics. Intravenous ketamine is being developed and tested for the treatment of posttraumatic stress disorder (PTSD).

All subjects will be administered the study medication by the study anesthesiologists and under the direct supervision of the investigator or designee. On all dosing days, all subjects must remain at the clinical site until at least 4 hours post-dose (or longer if required for study procedures) and will be accompanied by a responsible adult when discharged from the clinical site. The end of study will occur when the last subject in the trial completes his/her last study assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Repeated-Dose Intravenous Ketamine for PTSD
• Study Start Date: May 18, 2015
• Actual Primary Completion Date: Jan 27, 2020
• Actual Study Completion Date: Jan 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental ketamine group This arm will receive 0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	Drug: Ketamine; This arm will receive 0.5mg/kg repeated dose ketamine (6 intravenous infusions, 3 per week for 2 weeks).; Other Names: Generic only
Active Comparator: Active control midazolam group This arm will receive 0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).	Drug: Midazolam; This arm will receive 0.045mg/kg repeated dose intravenous midazolam (6 intravenous infusions, 3 per week for 2 weeks).; Other Names: Generic only

Outcome Measures

Primary Outcome Measures

1. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) [2 weeks after the first infusion]

   full range score from 0-80, with higher scores indicating greater PTSD symptoms

Secondary Outcome Measures

1. The Impact of Event Scale - Revised (IES-R) [24 hours after the first drug infusion]

   full range score from 0-88, with higher scores indicating greater PTSD symptoms

2. Montgomery Asberg Depression Rating Scale (MADRS) [24 hours after the first drug infusion]

   full range score from 0-60, with higher scores indicating greater depressive symptoms

3. Montgomery Asberg Depression Rating Scale (MADRS) [2 weeks after the first drug infusion]

   full range score from 0-60, with higher scores indicating greater depressive symptoms

4. Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR) [2 weeks after the first drug infusion]

   full range score from 0-27, with higher scores indicating greater depressive symptoms

5. Number of Participants With Patient-Rated Inventory of Side Effects (PRISE) [up to 21 weeks]

   All side effects listed in Adverse Event section.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women, 18-65 years of age;

• Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document;

• Participants must fulfill DSM-5 criteria for current civilian or combat-related PTSD

• Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year);

• Women of childbearing potential must have a negative pregnancy test at screening and prior to each intravenous infusion;

• Participants must be able to identify a family member, physician, or friend (i.e. someone who knows them well) who will participate in a Treatment Contract (and e.g. contact the study physician on their behalf in case manic symptoms or suicidal thoughts develop).

Exclusion criteria:

• Women who plan to become pregnant, are pregnant or are breast-feeding

• Serious, unstable medical illnesses such as hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, including gastro-esophageal reflux disease, obstructive sleep apnea, history of difficulty with airway management during previous anesthetics, ischemic heart disease and uncontrolled hypertension, and history of severe head injury;

• Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;

• Renal impairment, as reflected by a BUN >20 mg/dL, and/or creatinin clearance of >1.3 mg/dL;

• Thyroid impairment, as reflected by TSH> 4.2 mU/L Patients with uncorrected hypothyroidism or hyperthyroidism;

• Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first infusion day;

• Use of evidence-based individual psychotherapy (such as prolonged exposure) during the study;

• History of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome; History of one or more seizures without a clear and resolved etiology;

• History of (hypo)mania;

• Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder;

• Drug or alcohol abuse or dependence within the preceding 3 months

• Previous recreational use of ketamine or PCP;

• Current diagnosis of bulimia nervosa or anorexia nervosa;

• Diagnosis of schizotypal or antisocial personality disorder

• Patients judged clinically to be at serious and imminent suicidal or homicidal risk.

• A blood pressure of one reading over 160/90 or two separate readings over 140/90 at screen or baseline visits

• Patients who report current treatment with a benzodiazepine, an opioid medication, or a mood stabilizer (such as valproic acid or lithium) within 2 weeks prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression and Anxiety Center (DAC)	New York	New York	United States	10029

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Adriana Feder, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 24, 2020

More Information

Publications

None provided.

• Responsible Party: Adriana Feder, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02397889
• Other Study ID Numbers: GCO 15-0265
• First Posted: Mar 25, 2015
• Last Update Posted: Mar 11, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Adriana Feder, Associate Professor, Icahn School of Medicine at Mount Sinai: posttraumatic stress disorder; PTSD; ketamine; trauma; treatment; New York; NYC
• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Midazolam; Ketamine

Study Results

Participant Flow

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Period Title: Overall Study
STARTED	15	15
COMPLETED	14	15
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group	Total
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).	Total of all reporting groups
Overall Participants	15	15	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.3 (13.8)	38.5 (13.0)	38.9 (13.2)
Sex/Gender, Customized (Count of Participants)
Females	13 86.7%	10 66.7%	23 76.7%
Males	1 6.7%	5 33.3%	6 20%
Other	1 6.7%	0 0%	1 3.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 20%	3 20%	6 20%
Not Hispanic or Latino	11 73.3%	11 73.3%	22 73.3%
Unknown or Not Reported	1 6.7%	1 6.7%	2 6.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 13.3%	3 20%	5 16.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 13.3%	3 20%	5 16.7%
White	9 60%	7 46.7%	16 53.3%
More than one race	2 13.3%	1 6.7%	3 10%
Unknown or Not Reported	0 0%	1 6.7%	1 3.3%
Current treatment with psychotropic medication (Count of Participants)
Count of Participants [Participants]	7 46.7%	6 40%	13 43.3%
Clinician Administered PTSD Scale (CAPS-5) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	41.9 (6.1)	40.1 (5.9)	40.9 (5.9)
The Impact of Events Scale - Revised (IES-R) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	41.4 (14.0)	48.3 (20.1)	44.8 (17.3)
Montgomery Asberg Depression Rating Scale (MADRS) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.9 (6.8)	26.9 (7.7)	27.4 (7.2)
Montgomery Asberg Depression Rating Scale (MADRS) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.4 (6.6)	25.3 (9.0)	25.8 (7.8)
Duration of PTSD (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.1 (17.8)	14.6 (7.8)	14.9 (13.5)

Outcome Measures

1. Primary Outcome

Title	Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Description	full range score from 0-80, with higher scores indicating greater PTSD symptoms
Time Frame	2 weeks after the first infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	22.5 (14.4)	33.2 (11.8)

2. Secondary Outcome

Title	The Impact of Event Scale - Revised (IES-R)
Description	full range score from 0-88, with higher scores indicating greater PTSD symptoms
Time Frame	24 hours after the first drug infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	19.7 (15.2)	24.8 (13.1)

3. Secondary Outcome

Title	Montgomery Asberg Depression Rating Scale (MADRS)
Description	full range score from 0-60, with higher scores indicating greater depressive symptoms
Time Frame	24 hours after the first drug infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	16.5 (9.6)	17.1 (9.4)

4. Secondary Outcome

Title	Montgomery Asberg Depression Rating Scale (MADRS)
Description	full range score from 0-60, with higher scores indicating greater depressive symptoms
Time Frame	2 weeks after the first drug infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	14.7 (12.1)	21.9 (8.5)

5. Secondary Outcome

Title	Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR)
Description	full range score from 0-27, with higher scores indicating greater depressive symptoms
Time Frame	2 weeks after the first drug infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Mean (Standard Deviation) [score on a scale]	6.6 (7.1)	6.7 (5.4)

6. Secondary Outcome

Title	Number of Participants With Patient-Rated Inventory of Side Effects (PRISE)
Description	All side effects listed in Adverse Event section.
Time Frame	up to 21 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental Ketamine Group	Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).	0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
Measure Participants	15	15
Count of Participants [Participants]	15 100%	15 100%

Adverse Events

Time Frame	up to 21 weeks
Arm/Group Title	Experimental Ketamine Group		Active Control Midazolam Group
Arm/Group Description	0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).		0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).
All Cause Mortality
	Experimental Ketamine Group		Active Control Midazolam Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Experimental Ketamine Group		Active Control Midazolam Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Experimental Ketamine Group		Active Control Midazolam Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		15/15 (100%)
Cardiac disorders
Palpitation	1/15 (6.7%)		1/15 (6.7%)
Eye disorders
Blurred vision	10/15 (66.7%)		0/15 (0%)
Gastrointestinal disorders
Diarrhea	3/15 (20%)		4/15 (26.7%)
Dry mouth	2/15 (13.3%)		0/15 (0%)
Nausea/Vomiting	7/15 (46.7%)		6/15 (40%)
General disorders
Difficulty sleeping	2/15 (13.3%)		0/15 (0%)
Sleeping too much	1/15 (6.7%)		0/15 (0%)
Anxiety	1/15 (6.7%)		0/15 (0%)
Poor concentration	4/15 (26.7%)		1/15 (6.7%)
Fatigue	7/15 (46.7%)		14/15 (93.3%)
Decreased energy	1/15 (6.7%)		1/15 (6.7%)
Other	15/15 (100%)		10/15 (66.7%)
Nervous system disorders
Headache	7/15 (46.7%)		6/15 (40%)
Tremors	0/15 (0%)		1/15 (6.7%)
Dizziness	6/15 (40%)		2/15 (13.3%)
Renal and urinary disorders
Difficulty urinating	1/15 (6.7%)		1/15 (6.7%)
Painful urination	0/15 (0%)		1/15 (6.7%)
Frequent urination	1/15 (6.7%)		0/15 (0%)
Reproductive system and breast disorders
Loss of sexual desire	1/15 (6.7%)		0/15 (0%)
Trouble achieving orgasm	1/15 (6.7%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Rash	1/15 (6.7%)		0/15 (0%)
Increased persipiration	1/15 (6.7%)		0/15 (0%)
Itching	0/15 (0%)		1/15 (6.7%)

Limitations/Caveats

Exclusion of patients with comorbid psychotic, bipolar, or current alcohol or substance use disorders to protect against worsening of psychotic symptoms or abuse potential, which may limit generalizability of our findings to individuals with PTSD and these comorbid disorders.

More Information

Certain Agreements

All Principal Investigators ARE 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.