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

NCT02397889 | Completed Phase 2 Results DMC

• 1 other identifier: GCO 15-0265
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Posttraumatic Stress Disorder (PTSD)

Keywords

posttraumatic stress disorder; PTSD; ketamine; trauma; treatment; New York; NYC

Outcome Measures

Primary Outcomes (1)

• Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

  full range score from 0-80, with higher scores indicating greater PTSD symptoms

  2 weeks after the first infusion

Secondary Outcomes (5)

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

  24 hours after the first drug infusion

• Montgomery Asberg Depression Rating Scale (MADRS)

  24 hours after the first drug infusion

• Montgomery Asberg Depression Rating Scale (MADRS)

  2 weeks after the first drug infusion

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

  2 weeks after the first drug infusion

• Number of Participants With Patient-Rated Inventory of Side Effects (PRISE)

  up to 21 weeks

Study Arms (2)

Experimental ketamine group

EXPERIMENTAL

This arm will receive 0.5mg/kg repeated dose ketamine (6 infusions, 3 per week for 2 weeks).

Drug: Ketamine

Active control midazolam group

ACTIVE COMPARATOR

This arm will receive 0.045mg/kg repeated dose midazolam (6 infusions, 3 per week for 2 weeks).

Drug: Midazolam

Interventions

Ketamine DRUG

This arm will receive 0.5mg/kg repeated dose ketamine (6 intravenous infusions, 3 per week for 2 weeks).

Also known as: Generic only

Experimental ketamine group

Midazolam DRUG

This arm will receive 0.045mg/kg repeated dose intravenous midazolam (6 intravenous infusions, 3 per week for 2 weeks).

Also known as: Generic only

Active control midazolam group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Depression and Anxiety Center (DAC)

New York, New York, 10029, United States

Location

Related Publications (1)

• Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021 Feb 1;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596. Epub 2021 Jan 5.

  PMID: 33397139 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Wounds and Injuries

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Exclusion of patients with comorbid psychotic, bipolar, or current alcohol or substance use disorders to protect against worsening of psychotic symptoms or abuse potential, which may limit generalizability of our findings to individuals with PTSD and these comorbid disorders.

Results Point of Contact

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

adriana.feder@mssm.edu

212-659-9279

Study Officials

• Adriana Feder, 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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: March 25, 2015
• Study Start: May 18, 2015
• Primary Completion: January 27, 2020
• Study Completion: January 27, 2020
• Last Updated: March 11, 2021
• Results First Posted: February 11, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)