Clinical Trial Details
— Status: Terminated
Administrative data
NCT number |
NCT04712071 |
Other study ID # |
H-46289 |
Secondary ID |
|
Status |
Terminated |
Phase |
Early Phase 1
|
First received |
|
Last updated |
|
Start date |
February 1, 2021 |
Est. completion date |
February 16, 2022 |
Study information
Verified date |
February 2022 |
Source |
Baylor College of Medicine |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
Description:
Recruitment for this study starts after protocol approval by the BCM IRB, MEDVAMC R&D, and
DoD HRPO. All study procedures are for research only.
Potential subjects will be recruited (i) from the Houston community with advertisements in
local papers and social media, and with flyers at BCM and MEDVAMC; (ii) among veterans from
the 1990-1991 Gulf War who participated in protocol H-40948 and who consented to be
recontacted for future studies; (iii) among veterans from the 1990-1991 Gulf War who
voluntarily registered in the Gulf War Registry (GWR) because of concerns of possible Gulf
War Illness (GWI). Individuals under category (i) will contact us. Individuals under category
(ii) will be contacted by phone or text. Individuals under category (iii) will be contacted
by letter and, after a 10-day non-response, by phone. Before sending a letter, names in the
GWR will be matched with those in CPRS. If in CRPS, medical information will be reviewed to
determine study eligibility; if apparently eligible, the letter will be send. If an
individual is not in CPRS, the letter will be send. The letter is uploaded in section S.
For the phone call, after providing verbal consent, veterans who are interested in the study,
and who did not participate in protocol H-40948, will undergo an in-depth phone pre-screen to
determine eligibility. The phone pre-screen inventories symptoms of Gulf War Illness and
military history with the Gulf War Military and Health Questionnaire.
This study consists of 3 phases: screening, infusion of ketamine, telephone follow-up.
For phase 1, eligible subjects will provide a urine sample for drug and pregnancy testing,
undergo blood pressure testing, will undergo an EKG, will have to provide a 20 ml (2 tsp)
blood sample collected for clinical labs (an additional 10 ml (2 tsp) is optional and will be
banked for future research), and will visit with a study physician for a medical examination.
Finally, we will go over the Gulf War Military and Health Questionnaire assessed during the
phone-screen. Total time of phase 1 is 4 to 5 hours.
If qualified for the study, subjects will be scheduled for phase 2: the administration of a
single intravenous infusion of 0.5 mg/kg of ketamine. For phase 2, veterans will need to fast
for at least 8 hours before the infusion; they can take their medications as prescribed. At
arrival at the study site, subjects have to provide a urine sample for drug and pregnancy
testing. We will go over their medical information collected in phase 1 to inventory changes,
and they will undergo testing of vital signs. Before the infusion at 10 am, subjects will be
asked to fill out Gulf War Military and Health Questionnaire (24 hours symptoms). A baseline
of possible side effects is established with the CADSS which assess dissociative states.
Finally, EEG is collected from the scalp using 4-minute resting EEG (eyes-open/eyes-closed)
and 15-minute passive computer paradigm with auditory 85-dB click trains. The infusion of 0.5
mg/kg ketamine is prepared by the MEDVAMC Research Pharmacy. Ketamine is dissolved in 0.9%
saline in a bag of saline with a total volume of 100 mL, and administered with an infusion
pump at a constant rate. An anesthesiologist will place an indwelling catheter. We will first
collect an 10 ml (2 tsp) sample of blood for pro-inflammatory cytokine. Next, the catheter is
used for the infusion, which lasts 40 minutes. The EEG and blood collection is repeated at
35-minutes (the peak of ketamine concentration), and again one and two hours later. Subjects
will not be discharged before four hours after the end of the infusion.
For phase 3, as part of the research procedures, subjects will be contacted by telephone or
telehealth services at a pre-arranged time of mutual convenience on days 1, 2 and 7 after the
infusion to inventory 24-hr symptoms with the Gulf War Military and Health Questionnaire.
This procedure lasts about 45 minutes to complete