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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Mount Sinai School of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dennis Charney, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00749203
First received: September 5, 2008
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

The objective of the proposed study is to test if a single IV dose of ketamine (0.5 mg/kg) decreases symptoms of PTSD.


Condition Intervention Phase
Stress Disorders, Post-Traumatic
PTSD
Depression
Anxiety Disorder
Drug: Midazolam
Drug: Ketamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Impact of Event Scale - Revised (IES-R) [ Time Frame: 24 hours after infusion ] [ Designated as safety issue: No ]
    Self-report questionnaire measuring PTSD symptoms


Secondary Outcome Measures:
  • Clinician-Administered PTSD Scale (CAPS) [ Time Frame: 7 days after infusion ] [ Designated as safety issue: No ]
    Clinician-administered structured interview measuring PTSD symptoms

  • Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) [ Time Frame: 24 hours after infusion ] [ Designated as safety issue: No ]
    Self-report questionnaire measuring depressive symptoms

  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours after infusion ] [ Designated as safety issue: No ]
    Clinician-administered questionnaire measuring depressive symptoms

  • Hopkins Verbal Learning Test (HVLT) [ Time Frame: 20 to 40 minutes after infusion ] [ Designated as safety issue: No ]
    Repeatable test of memory acquisition and delayed recall of words


Estimated Enrollment: 40
Study Start Date: January 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes
Drug: Ketamine
Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes
Other Name: Racemic ketamine hydrochloride
Active Comparator: Midazolam
single dose 0.045 mg/kg IV infused over 40 minutes
Drug: Midazolam
single dose 0.045 mg/kg IV infused over 40 minutes

Detailed Description:

PTSD is a debilitating anxiety disorder characterized by intrusive re-experiences of the traumatic events, avoidance of situations and stimuli that could serve as reminders of these events, and feeling jumpy or easily startled. Patients with PTSD are often also depressed, and many have significant memory impairments. Existing drug treatments are unsuccessful in a majority of patients, especially in those with combat-related PTSD.

Our aim is to test the effectiveness of a potential new drug for PTSD, ketamine. For many years, intravenous ketamine has been extensively used for anesthesia. More recently, using doses lower than those used in anesthesia, a single ketamine infusion was shown to rapidly reduce depressed mood as well as anxiety in patients with severe depression. Some clinical evidence of potential efficacy in depressed patients with co-morbid PTSD also exists.

Adverse effects in these studies have been limited to feeling intoxicated and having increased blood pressure during the infusion.

In the present study, we expect a single ketamine infusion to reduce core PTSD symptoms. In addition, in those patients with PTSD who are depressed, we expect ketamine to reduce depressed mood.

Finally, ketamine is known to impair memory function temporarily. We will also test if the extent of ketamine-induced memory impairment during the infusion can predict how well people do after the infusion. Forty patients with PTSD (with and without combat-related trauma histories) will be tested, using a design that will compare the effectiveness of intravenous ketamine to that of midazolam, another anesthetic drug without any known long-term effects on anxiety, depressed mood, and memory function. If ketamine is found to have the expected effects, future studies may explore additional benefits of repeated infusions and / or alternatives to intravenous drug administration. Our study may contribute to improved function of patients with PTSD by providing a new means to rapidly treat their debilitating symptoms.

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women, 21-55 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-IV criteria for current civilian or combat-related PTSD, based on clinical assessment by a study psychiatrist and on the CAPS (score must be at least 50 at screening and prior to each infusion - this is done to ensure at least moderate severity and to safeguard against high placebo response rates); additionally, clinicians will use clinical judgment to assess if patients are symptomatic enough to receive each infusion
  • 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 pre-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 (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 infusion day;
  • Use of evidence-based individual psychotherapy (such as prolonged exposure) and other non-pharmacological treatments during the study;
  • Histories 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 (given that this might otherwise contribute to their symptoms, however, a rather narrow time period was chosen such as 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);
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749203

Contacts
Contact: Julia Morgan 212-241-7906 julia.morgan@mssm.edu
Contact: Adriana Feder, MD 212-659-9145

Locations
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Principal Investigator: Dennis Charney, MD         
Sponsors and Collaborators
Dennis Charney
Investigators
Principal Investigator: Dennis Charney, MD Mount Sinai School of Medicine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dennis Charney, Dean, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00749203     History of Changes
Other Study ID Numbers: GCO 07-1199, PT074949, IF1336344, A-15236
Study First Received: September 5, 2008
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Stress Disorders, Post-Traumatic
PTSD
anxiety disorder
ketamine
depression
depressed mood

Additional relevant MeSH terms:
Anxiety Disorders
Depression
Depressive Disorder
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Mental Disorders
Behavioral Symptoms
Mood Disorders
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents

ClinicalTrials.gov processed this record on August 26, 2014