Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

NCT04032301 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PSYCH-2019-28086
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Co-occurring post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) is the most common response to trauma; it is associated with poor clinical outcomes and substantial human disability. Veterans with both PTSD and MDD (PTSD+MDD) have been shown to be at much greater suicidal risk than individuals with only one of these disorders. Ketamine given as repeated infusions has been shown to be effective in rapidly reducing PTSD and MDD symptoms in treatment resistant PTSD+MDD individuals. However, knowledge about the mechanisms underlying comorbid PTSD and MDD remain limited. The purpose of this study is to use repeated ketamine infusions as a probe to validate a model of PTSD+MDD that focuses on neuroanatomy and executive functioning.

Conditions

Post-Traumatic Stress Disorders; Major Depressive Disorder

Keywords

ketamine; stress disorders, post-traumatic; stress disorders, traumatic; anxiety disorders; mental disorders; adjuvants, anesthesia; analgesics; anesthetics; anesthetics, dissociative; anesthetics, general; anesthetics, intravenous; excitatory amino acid agents; excitatory amino acid antagonists; hypnotics and sedatives; molecular mechanisms of pharmacological action; neurotransmitter agents; peripheral nervous system agents; pharmacologic actions; physiological effects of drugs; psychotropic drugs; sensory system agents; central nervous system agents; central nervous system depressants; depression; depressive disorder; depressive disorder, treatment-resistant; behavioral symptoms; mood disorders; therapeutic uses

Outcome Measures

Primary Outcomes (2)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Change in major depressive disorder symptoms over the course of the intervention.

  At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.

• PTSD Symptom Scale-Interview for DSM-5 (PSS-I-5)

  Change in post-traumatic stress disorder symptoms over the course of the intervention.

  At baseline, 60 minutes pre-infusion, 24 hours post-infusion, and after infusion series up to 2 months.

Study Arms (2)

Intravenous ketamine infusions

EXPERIMENTAL

Six infusions of 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.

Drug: Ketamine

Intravenous saline infusions

PLACEBO COMPARATOR

Six infusions of normal saline solution over 3 weeks.

Other: Normal Saline

Interventions

Ketamine DRUG

Six infusions of intravenous 0.5 mg/kg ketamine hydrochloride solution over 3 weeks.

Also known as: Ketamine Hydrochloride

Intravenous ketamine infusions

Normal Saline OTHER

Six infusions of intravenous normal saline solution over 3 weeks.

Also known as: Sodium Chloride in Water

Intravenous saline infusions

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female/Male veterans
• to 75 years old
• Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
• Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\]
• If applicable, 6 weeks of stable antidepressants/augmenting agents
• Sixth grade reading level
• Ability to provide consent
• Female/Male veterans
• to 75 years old
• Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features
• Does not meet DSM-5 criteria for chronic PTSD or subthreshold PTSD
• Not on medications for managing a psychiatric indication
• Sixth grade reading level
• Ability to provide consent
• Female/Male veterans

You may not qualify if:

• Inability or unwillingness to provide written informed consent
• Moderate/severe cognitive impairment
• Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
• History of moderate or severe traumatic brain injury
• History of comorbid substance disorder within 1 month of screening
• Prior use of ketamine as an antidepressant
• Clinically unstable medical illness
• For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study
• Imminent risk of suicidal/homicidal ideation and/or behavior
• Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)
• Inability or unwillingness to provide written informed consent
• Moderate/severe cognitive impairment
• History of any major medical or psychiatric disorders
• Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition
• History of moderate or severe traumatic brain injury

Sponsors & Collaborators

• University of Minnesota: lead
• Minneapolis Veterans Affairs Medical Center: collaborator

Study Sites (1)

Minneapolis Veterans Affairs Health Care System

Minneapolis, Minnesota, 55417, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depressive Disorder, Major; Stress Disorders, Traumatic; Anxiety Disorders; Mental Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders

Interventions

Ketamine; Saline Solution; Sodium Chloride; Water

Condition Hierarchy (Ancestors)

Trauma and Stressor Related Disorders; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Hydroxides; Alkalies; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Cristina S Albott, MD, MA

  Minneapolis Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Experimental versus Placebo

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 25, 2019
• Study Start: September 30, 2019
• Primary Completion: September 16, 2024
• Study Completion: November 10, 2024
• Last Updated: June 27, 2025

Record last verified: 2025-06

Locations

US (1)