Effects of a Single Dose of Intravenous Ketamine on Symptoms of Gulf War Illness in 1990-1991 Gulf War Veterans
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Change in 40Hz Auditory steady state response (ASSR) EEG power
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Military veterans who served for any period of time in the Gulf War Theater of Operations between August of 1990 and July of
- •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.
排除标准
- •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.
- •Uncontrolled hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg).
- •Family history or own history of schizophrenia or psychosis.
- •For at least two weeks before ketamine infusion, use of:
- •Antibiotics
- •Antiviral medication
- •anti-inflammatory medications (including NSAIDS) for at least two weeks before ketamine infusion.
- •Being pregnant or breastfeeding.
研究组 & 干预措施
Ketamine
40 minutes intravenous infusion of 0.5 mg/kg ketamine.
干预措施: Ketamine Hydrochloride (Drug)
结局指标
主要结局
Change in 40Hz Auditory steady state response (ASSR) EEG power
时间窗: pre-treatment baseline, 35 minutes after start of infusion (close to ketamine peak) and 95 minutes after start of infusion
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.
次要结局
- 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 Gulf War Military and Health Questionnaire(pre-treatment baseline and days 1, 2 and 7 after the infusion)
- Change in CADSS dissociative states scale(Pre-treatment baseline, and 1 hour, 2 hours and 4 hours after start of infusion)
研究者
Marijn Lijffijt, PhD
Assistant Professor
Baylor College of Medicine