PTSDPhase 2/3NCT02398136
To Test the Potential Efficacy of Repeated Intranasal Administration of Ketamine as a Treatment for PTSD
A Phase 2/3 study testing Ketamine and Midazolam in people with PTSD, run by Adriana Feder.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- PTSD
- What is being tested?
- Ketamine and Midazolam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2014to Dec 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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;
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- 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.
About this study
Official title: Randomized Controlled Trial of Repeated Dose Ketamine in Post Traumatic Stress Disorder (PTSD)
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.
Read the 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.
- Conditions
- PTSD
- Keywords
- intervention, ketamine, PTSD, treatment, posttraumatic stress disorder
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Intranasal ketamine up to 75 mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks. Receives: Drug: Ketamine |
| Midazolam | Active comparator | Intranasal midazolam 3.75mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours
Secondary outcomes (5)
Clinician Administered PTSD Scale (CAPS)
The CAPS is a structured clinical interview designed to assess the essential features of PTSD.
Measured: up to 4 weeks
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.
Measured: 24 hours
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.
Measured: 24 hours
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.
Measured: 24 hours
Sheehan Disability Scale (SDS)
The SDS is a 10 point visual analog scale developed to assess functional impairment.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startDec 2014
- Primary completionDec 2014
- Study completionDec 2014
Why it stopped: FDA and IRB recommended different mode of medication administration
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Adriana Feder
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Adriana Feder, Icahn School of Medicine at Mount Sinai
- Investigators
- Adriana Feder, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398136
- Sponsor's protocol ID
- GCO 14-1781
- Status last verified
- Mar 2015
- First submitted
- 7 Nov 2014
- Last updated
- 25 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Repeated Dose Ketamine in Post Traumatic Stress Disorder (PTSD)
- ClinicalTrials.gov ID
- NCT02398136
- Acronym / sponsor ID
- GCO 14-1781
- Conditions
- PTSD
- Keywords
- intervention, ketamine, PTSD, treatment, posttraumatic stress disorder
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: FDA and IRB recommended different mode of medication administration
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Adriana FederUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineIntranasal ketamine up to 75 mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks. |
| Midazolam | Active comparator | Drug: MidazolamIntranasal midazolam 3.75mg, delivered over 20 minutes, frequency: 3x/week for 4 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Intranasal ketamine | Drug | Ketamine |
| MidazolamAlso: Placebo | Drug | Midazolam |
Primary outcome
Impact of Events Scale-Revised (IES-R)
Time frame: 24 hours
The IES-R is used to self-report measures of stress reactions to traumatic events. It measures both intrusion and avoidance.
5 secondary outcomes
Clinician Administered PTSD Scale (CAPS)
Time frame: up to 4 weeks
Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)
Time frame: 24 hours
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 24 hours
Patient-Rated Inventory of Side Effects (PRISE)
Time frame: 24 hours
Sheehan Disability Scale (SDS)
Time frame: 24 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana Feder, MD principal investigator
Icahn School of Medicine at Mount Sinai
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ketamine and Midazolam in people with PTSD, run by Adriana Feder.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of Events Scale-Revised (IES-R) (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2015.