To Test the Potential Efficacy of Repeated Intranasal Administration of Ketamine as a Treatment for PTSD
Primary Purpose
PTSD
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ketamine
Midazolam
Sponsored by
About this trial
This is an interventional treatment trial for PTSD focused on measuring intervention, ketamine, PTSD, treatment, posttraumatic stress disorder
Eligibility Criteria
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, based on clinical assessment by a study psychiatrist and on the CAPS -this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
- 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 intranasal administration;
- 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 (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
- 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;
- Patients with uncorrected hypothyroidism or hyperthyroidism;
- Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first intranasal administration 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; a rather narrow time period was chosen, however, in order to allow participation by individuals with a history of substance abuse or dependence problems that could be secondary to their PTSD, and to more closely approximate patients seen in real-world settings; this is the same period of time that we used in our recently completed study of IV ketamine for PTSD.
- Previous recreational use of ketamine or PCP;
- Current diagnosis of bulimia nervosa or anorexia nervosa;
- Diagnosis of schizotypal or antisocial personality disorder (since these are known to reduce the possibility of study completion); other Axis II diagnoses will be allowed;
- 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; patients taking stable doses of antidepressant medication for 3 months prior to randomization will be allowed.
- For subjects who may participate in the MRI portion of the study, claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ketamine
Midazolam
Arm Description
Intranasal ketamine up to 75 mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks.
Intranasal midazolam 3.75mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks.
Outcomes
Primary Outcome Measures
Impact of Events Scale-Revised (IES-R)
The IES-R is used to self-report measures of stress reactions to traumatic events. It measures both intrusion and avoidance.
Secondary Outcome Measures
Clinician Administered PTSD Scale (CAPS)
The CAPS is a structured clinical interview designed to assess the essential features of PTSD.
Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)
The QIDS-SR is a 16-item self-rated instrument designed to assess the severity of depressive symptoms present in the past seven days.
Montgomery Asberg Depression Rating Scale (MADRS)
The MADRS is a 10-item instrument used for the evaluation of depressive symptoms and for the assessment of any changes to those symptoms.
Patient-Rated Inventory of Side Effects (PRISE)
PRISE is a 7-item self report used to qualify side effects by identifying and evaluating the tolerability of each symptoms.
Sheehan Disability Scale (SDS)
The SDS is a 10 point visual analog scale developed to assess functional impairment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02398136
Brief Title
To Test the Potential Efficacy of Repeated Intranasal Administration of Ketamine as a Treatment for PTSD
Official Title
Randomized Controlled Trial of Repeated Dose Ketamine in Post Traumatic Stress Disorder (PTSD)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Withdrawn
Why Stopped
FDA and IRB recommended different mode of medication administration
Study Start Date
December 2014 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Adriana Feder
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to see whether ketamine, when given repeatedly via the nose (intranasally), 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.
Detailed Description
The objective of the present research protocol, a parallel-arm, double-blind, randomized controlled clinical trial, is to test the efficacy of repeated intranasal administration of the glutamatergic NMDA receptor antagonist ketamine in providing (1) rapid relief of and (2) sustained improvement in core PTSD symptoms and co-morbid depressive symptoms in patients with chronic PTSD. The effects of ketamine will be compared with those of repeated intranasal administration of the benzodiazepine anesthetic midazolam, which mimics some of the acute subjective effects of ketamine but is expected to have lesser or less sustained anxiolytic effect, and no sustained antidepressant effect.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PTSD
Keywords
intervention, ketamine, PTSD, treatment, posttraumatic stress disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ketamine
Arm Type
Experimental
Arm Description
Intranasal ketamine up to 75 mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks.
Arm Title
Midazolam
Arm Type
Active Comparator
Arm Description
Intranasal midazolam 3.75mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Intranasal ketamine
Intervention Type
Drug
Intervention Name(s)
Midazolam
Other Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Impact of Events Scale-Revised (IES-R)
Description
The IES-R is used to self-report measures of stress reactions to traumatic events. It measures both intrusion and avoidance.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Clinician Administered PTSD Scale (CAPS)
Description
The CAPS is a structured clinical interview designed to assess the essential features of PTSD.
Time Frame
up to 4 weeks
Title
Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)
Description
The QIDS-SR is a 16-item self-rated instrument designed to assess the severity of depressive symptoms present in the past seven days.
Time Frame
24 hours
Title
Montgomery Asberg Depression Rating Scale (MADRS)
Description
The MADRS is a 10-item instrument used for the evaluation of depressive symptoms and for the assessment of any changes to those symptoms.
Time Frame
24 hours
Title
Patient-Rated Inventory of Side Effects (PRISE)
Description
PRISE is a 7-item self report used to qualify side effects by identifying and evaluating the tolerability of each symptoms.
Time Frame
24 hours
Title
Sheehan Disability Scale (SDS)
Description
The SDS is a 10 point visual analog scale developed to assess functional impairment.
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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, based on clinical assessment by a study psychiatrist and on the CAPS -this is done to ensure at least moderate severity and to safeguard against high placebo response rates;
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 intranasal administration;
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 (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
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;
Patients with uncorrected hypothyroidism or hyperthyroidism;
Hormonal treatment (e.g., estrogen) started in the 3 months prior to the first intranasal administration 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; a rather narrow time period was chosen, however, in order to allow participation by individuals with a history of substance abuse or dependence problems that could be secondary to their PTSD, and to more closely approximate patients seen in real-world settings; this is the same period of time that we used in our recently completed study of IV ketamine for PTSD.
Previous recreational use of ketamine or PCP;
Current diagnosis of bulimia nervosa or anorexia nervosa;
Diagnosis of schizotypal or antisocial personality disorder (since these are known to reduce the possibility of study completion); other Axis II diagnoses will be allowed;
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; patients taking stable doses of antidepressant medication for 3 months prior to randomization will be allowed.
For subjects who may participate in the MRI portion of the study, claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adriana Feder, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
To Test the Potential Efficacy of Repeated Intranasal Administration of Ketamine as a Treatment for PTSD
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