Posttraumatic Stress Disorder (PTSD)
Conditions
Keywords
posttraumatic stress disorder, PTSD, ketamine, trauma, treatment, New York, NYC
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.
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.
Interventions
DRUGKetamine
This arm will receive 0.5mg/kg repeated dose ketamine (6 intravenous infusions, 3 per week for 2 weeks).
DRUGMidazolam
This arm will receive 0.045mg/kg repeated dose intravenous midazolam (6 intravenous infusions, 3 per week for 2 weeks).
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Number of Participants With Patient-Rated Inventory of Side Effects (PRISE) | up to 21 weeks | All side effects listed in Adverse Event section. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Ketamine Group 0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks). | 15 |
| Active Control Midazolam Group 0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks). | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Active Control Midazolam Group | Experimental Ketamine Group | Total |
|---|---|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 13 | 39.3 years STANDARD_DEVIATION 13.8 | 38.9 years STANDARD_DEVIATION 13.2 |
| Clinician Administered PTSD Scale (CAPS-5) score | 40.1 units on a scale STANDARD_DEVIATION 5.9 | 41.9 units on a scale STANDARD_DEVIATION 6.1 | 40.9 units on a scale STANDARD_DEVIATION 5.9 |
| Current treatment with psychotropic medication | 6 Participants | 7 Participants | 13 Participants |
| Duration of PTSD | 14.6 years STANDARD_DEVIATION 7.8 | 15.1 years STANDARD_DEVIATION 17.8 | 14.9 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Montgomery Asberg Depression Rating Scale (MADRS) score | 25.3 units on a scale STANDARD_DEVIATION 9 | 26.4 units on a scale STANDARD_DEVIATION 6.6 | 25.8 units on a scale STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 16 Participants |
| Sex/Gender, Customized Females | 10 Participants | 13 Participants | 23 Participants |
| Sex/Gender, Customized Males | 5 Participants | 1 Participants | 6 Participants |
| Sex/Gender, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| The Impact of Events Scale - Revised (IES-R) | 48.3 units on a scale STANDARD_DEVIATION 20.1 | 41.4 units on a scale STANDARD_DEVIATION 14 | 44.8 units on a scale STANDARD_DEVIATION 17.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 15 / 15 | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
full range score from 0-80, with higher scores indicating greater PTSD symptoms
Time frame: 2 weeks after the first infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Ketamine Group | Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) | 22.5 score on a scale | Standard Deviation 14.4 |
| Active Control Midazolam Group | Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) | 33.2 score on a scale | Standard Deviation 11.8 |
Secondary
Montgomery Asberg Depression Rating Scale (MADRS)
full range score from 0-60, with higher scores indicating greater depressive symptoms
Time frame: 24 hours after the first drug infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Ketamine Group | Montgomery Asberg Depression Rating Scale (MADRS) | 16.5 score on a scale | Standard Deviation 9.6 |
| Active Control Midazolam Group | Montgomery Asberg Depression Rating Scale (MADRS) | 17.1 score on a scale | Standard Deviation 9.4 |
Secondary
Montgomery Asberg Depression Rating Scale (MADRS)
full range score from 0-60, with higher scores indicating greater depressive symptoms
Time frame: 2 weeks after the first drug infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Ketamine Group | Montgomery Asberg Depression Rating Scale (MADRS) | 14.7 score on a scale | Standard Deviation 12.1 |
| Active Control Midazolam Group | Montgomery Asberg Depression Rating Scale (MADRS) | 21.9 score on a scale | Standard Deviation 8.5 |
Secondary
Number of Participants With Patient-Rated Inventory of Side Effects (PRISE)
All side effects listed in Adverse Event section.
Time frame: up to 21 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Ketamine Group | Number of Participants With Patient-Rated Inventory of Side Effects (PRISE) | 15 Participants |
| Active Control Midazolam Group | Number of Participants With Patient-Rated Inventory of Side Effects (PRISE) | 15 Participants |
Secondary
Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR)
full range score from 0-27, with higher scores indicating greater depressive symptoms
Time frame: 2 weeks after the first drug infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Ketamine Group | Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR) | 6.6 score on a scale | Standard Deviation 7.1 |
| Active Control Midazolam Group | Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR) | 6.7 score on a scale | Standard Deviation 5.4 |
Secondary
The Impact of Event Scale - Revised (IES-R)
full range score from 0-88, with higher scores indicating greater PTSD symptoms
Time frame: 24 hours after the first drug infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental Ketamine Group | The Impact of Event Scale - Revised (IES-R) | 19.7 score on a scale | Standard Deviation 15.2 |
| Active Control Midazolam Group | The Impact of Event Scale - Revised (IES-R) | 24.8 score on a scale | Standard Deviation 13.1 |