Ketamine in Veterans With Gulf War Illness

NCT04712071 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: H-46289
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Up to one third of the 700,000 U.S. military veterans of the 1990-91 Gulf War have Gulf War Illness (GWI), a symptom complex characterized by a combination of chronic pain, cognitive impairment, debilitating fatigue, gastrointestinal complications, and other persistent symptoms. Epidemiologic studies of 1990-1991 Gulf War veterans have identified the short but intense combined exposure to insecticides (e.g., organophosphates, DEET, permethrin), pills with anti-nerve gas agent pyridostigmine bromide (PB), and low-level chemical nerve agents as likely candidates of GWI. Animal models have shown that these neurotoxicants could induce neuroinflammation which is marked by enhanced inflammatory cytokines, and activated microglia and astrocytes. Inflammation has been linked to GWI. Secondary effects of neuroinflammation and glia activation could be excessive glutamate-mediated neuronal activation. There is currently no treatment for symptoms of GWI. Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist. Besides blocking activation of NMDARs, a sub-anesthetic dose (0.5 mg/kg over 40 minutes) of ketamine could be an anti-inflammatory agent, and could protect microglia and astrocytes from being activated by inflammatory agents. This low dose of ketamine has also been shown to improve fatigue within 24 hours after a single infusion, and to improve inflammatory pain. This makes ketamine a feasible candidate for the treatment of inflammation-associated symptoms of GWI. This pilot study will examine if GWI is related to NMDAR functioning, testing effects of a single 40-minute intravenous infusion of 0.5 mg/kg of ketamine on GWI symptom severity in 21 veterans of the 1990-1991 Gulf War who meet Kansas case definition criteria of GWI.

Conditions

Gulf War Syndrome

Keywords

Gulf War Illness; Inflammation; N-methyl-D-aspartate; ketamine

Outcome Measures

Primary Outcomes (1)

• Change in 40Hz Auditory steady state response (ASSR) EEG power

  The 40Hz ASSR is an electrophysiology (EEG) paradigm that presents 1-sec trains of 1-ms 85dB clicks presented at 40Hz. Outcome measure is mean power across 32 - 42Hz averaged across fronto-central electrodes that are attached in a 64-channel electrode cap that is based on a 10-10 distribution.

  pre-treatment baseline, 35 minutes after start of infusion (close to ketamine peak) and 95 minutes after start of infusion

Secondary Outcomes (3)

• Change in Gulf War Military and Health Questionnaire

  pre-treatment baseline and days 1, 2 and 7 after the infusion

• Change in 4 minutes resting state EEG

  pre-treatment baseline, 35 minutes after start of infusion (close to ketamine peak) and 95 minutes after start of infusion

• Change in CADSS dissociative states scale

  Pre-treatment baseline, and 1 hour, 2 hours and 4 hours after start of infusion

Other Outcomes (1)

• Inflammatory cytokines and metabolites of ketamine in 10 mL blood sample: Exploratory

  Pre-treatment baseline, and 1 hour, 2 hours and 4 hours after start of infusion

Study Arms (1)

Ketamine

EXPERIMENTAL

40 minutes intravenous infusion of 0.5 mg/kg ketamine.

Drug: Ketamine Hydrochloride

Interventions

Ketamine Hydrochloride DRUG

Patients with a diagnosis of Gulf War Illness using Kansas Criteria will be enrolled to receive a single 40 minute infusion of 0.5 mg/kg ketamine.

Also known as: Ketelar

Ketamine

Eligibility Criteria

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

You may qualify if:

• Military veterans who served for any period of time in the Gulf War Theater of Operations between August of 1990 and July of 1991.
• Cases must meet Kansas GWI case definition criteria.
• Understand the study as described in the informed consent form, and be able to consent for study participation.

You may not qualify if:

• A physical or psychiatric illness explaining GWI case definition symptoms at the discretion of the PI.
• History of seizures.
• History of ECT or deep brain stimulation.
• History of head injury with loss-of-consciousness over 15 minutes or no recollection of events.
• Unstable serious illness at the discretion of the PI or study physician, including:
• hepatic disease
• renal disease
• gastroenterologic disease
• respiratory disease,
• cardiovascular disease (including ischemic heart disease)
• endocrinologic disease
• neurologic disease
• immunologic disease
• hematologic disease.
• Clinically significant EKG or laboratory values at the discretion of the study physician.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Michael E. DeBakey VA Medical Center: collaborator

Study Sites (1)

Marijn Lijffijt

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Persian Gulf Syndrome; Inflammation

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Occupational Diseases; War-Related Injuries; Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Marijn Lijffijt, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single group, single dose, open-label study

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: January 15, 2021
• Study Start: February 1, 2021
• Primary Completion: February 16, 2022
• Study Completion: February 16, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)