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

NCT00749203 | Completed Phase 2 Results DMC

• 4 other identifiers: GCO 07-1199PT074949IF1554104A-15236
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Stress Disorders, Post-Traumatic; PTSD; Depression; Anxiety Disorder

Keywords

Stress Disorders, Post-Traumatic; PTSD; anxiety disorder; ketamine; depression; depressed mood

Outcome Measures

Primary Outcomes (1)

• Impact of Event Scale - Revised (IES-R)

  A 22-item self-report questionnaire measuring PTSD symptoms. Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score ranging from 0 (not at all) to 88 (extremely)

  7 days after first infusion

Secondary Outcomes (4)

• Clinician-Administered PTSD Scale (CAPS)

  7 days after first infusion

• Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)

  24 hours after first infusion

• Montgomery-Asberg Depression Rating Scale (MADRS)

  24 hours after first infusion

• Hopkins Verbal Learning Test (HVLT)

  20 to 40 minutes after infusion

Study Arms (2)

Ketamine

EXPERIMENTAL

Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes

Drug: Ketamine

Midazolam

ACTIVE COMPARATOR

single dose 0.045 mg/kg IV infused over 40 minutes

Drug: Midazolam

Interventions

Midazolam DRUG

single dose 0.045 mg/kg IV infused over 40 minutes

Midazolam

Ketamine DRUG

Single dose 0.5 mg/kg IV (in the vein) infused over 40 minutes

Also known as: Racemic ketamine hydrochloride

Ketamine

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dennis Charney: lead
• United States Department of Defense: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (3)

• Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

  PMID: 16894061 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

  PMID: 10686270 BACKGROUND

• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

  PMID: 24740528 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depression; Anxiety Disorders; Consciousness Disorders

Interventions

Midazolam; Ketamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Several patients did not receive a second infusion per protocol because of sustained reduction in PTSD symptom levels . The study also does not address the safety or efficacy of ketamine in combination with other psychotropic medications in PTSD.

Results Point of Contact

• Title: Dr. Adriana Feder
• Organization: Icahn School of Medicine at Mount Sinai

adriana.feder@mssm.edu

212-241-1563

Study Officials

• Dennis Charney, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dean

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 9, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: February 14, 2018
• Results First Posted: February 14, 2018

Record last verified: 2018-02

Locations

US (1)