ELECTRIG: Evaluating Effects of Cranial Electrical Stimulation Therapy With Responsive Imaging in Gulf War Illness Pain and Comorbid Symptoms
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Change in Defense and Veterans Pain Rating Scale (DVPRS) from baseline
研究概览
简要总结
The main goal of the proposed study is to critically evaluate a nonpharmacological and readily available therapy, cranial electrical stimulation (CES) using Alpha-Stim™, and to discover the brain function mechanisms underlying Gulf War Illness-related Headache and Pain (GWI-HAP) and treatment response to CES.
For this objective, the investigators will employ an adaptive trial design as well as a neuroimaging technique using MRI, which has become the pre-eminent technique for assessing the integrity of brain function, connectivity, and organization in healthy brain and pathology.
详细描述
Gulf War Veterans are disproportionately plagued by fibromyalgia-like symptoms including headaches, joint, and muscle pain, known as gulf war illness pain or GWI-HAP. Treatment options are limited, and the neurobiology of these symptoms is poorly understood.
In this population, the investigators plan to test a portable, non-pharmacological, non-invasive therapy (Alpha-Stim™) that is FDA-cleared for anxiety, insomnia, and pain, and readily available for widespread implementation in the United States. This cranial electrical stimulation (CES) device has shown promising, though limited results for anxiety, insomnia, and pain. They also plan to employ magnetic resonance spectroscopy (MRS) to evaluate neuroinflammation.
Subjects will be male and females, age 40-80 years old, with a diagnosis of Gulf war illness. Subjects will be recruited by referral and posted flyers on Emory campus, ResearchMatch, the Gulf War Registry, and the Wounded Warriors' Program. The research team will not approach vulnerable populations including minors, prisoners, pregnant persons, neonates or human fetuses, wards of the state, or cognitively impaired persons. Recruitment, screening and enrollment will occur at the Emory clinics (EUHM and EUH) and the Human Subjects Research Building II.
This randomized, double-blind, sham-controlled study will compare the efficacy of "active" or true CES therapy to "sham" CES therapy. Participants will be randomized in a 1:1 ratio to true or sham CES (n=104 total; 52 true, 52 sham). Up to 130 subjects will be enrolled to achieve 104 treated subjects. Baseline assessments including quality of life questionnaires and pain assessments, in addition to MRI will be obtained prior to initiation of the intervention.
The participant will be trained in device usage and instructed to use the device each evening around the same time for 60 minutes (timer will be pre-set). They will also be provided detailed instructions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be male and female age 40-80 years old
- •Meet criteria for GWVI based on the CDC and Kansas Criteria for GWVI.
- •CDC: 1 or more from at least 2 of the following categories for ≥ 6 months): 1) fatigue 2) mood and cognition (symptoms of feeling depressed, difficulty in remembering or concentrating, feeling moody, feeling anxious, trouble in finding words, or difficulty in sleeping) 3) musculoskeletal (symptoms of joint pain, joint stiffness, or muscle pain
- •Kansas: 3 of 6 domains: 1) fatigue and sleep problems 2) pain symptoms 3) neurologic, cognitive, or mood symptoms 4) gastrointestinal symptoms 5) respiratory symptoms 6) skin symptoms chronic since
- •Symptom reporting must be in the absence of diagnosed exclusionary conditions; only respondents who have at least 1 moderately severe symptom or 2 or more symptoms within a group were considered to have a high level of symptoms in the group.
- •Subjects must self-report consistent, daily pain (greater than or equal to 4 on the DVPRS) >90 days (prior to enrollment)
- •Subjects must have intact skin free of infection at the site of electrode placement (earlobe).
- •Subjects must be willing to participate and understand the consent.
- •Subjects must be right-handed to provide consistency in brain structure and function.
排除标准
- •Subjects must not be currently pregnant since effects of fMRI and electrical current on the developing fetus are not well-known.
- •Subjects must not have a history of drug abuse or severe, uncontrolled psychiatric illness such as schizophrenia or major depressive disorder with suicidal ideation.
- •Subjects must not have psoriasis vulgaris or other skin conditions that may increase the risk of infection at the implantation site.
- •Subjects must not introduce new medications or treatments for symptoms during the study to prevent confounding results.
- •Subjects must not have severe anxiety, claustrophobia, or other conditions that may prevent their ability to lie at rest in an MRI scanner. This will be determined after discussion with the patient regarding their own perceived ability to lie at rest in an MRI scanner without the use of additional sedating medications.
- •Subjects must not have an implanted electrical device such as a surgically placed vagal stimulator, pacemaker, or spinal pain pump, which are not compatible with MRI.
- •Subjects must not have a history of seizures or neurologic conditions that may alter the structure of the brain.
- •Subjects must not be allergic to the metals used in electrodes for CES stimulation.
- •Subjects must not have a diagnosed autoimmune disease that better explains pain symptoms.
研究组 & 干预措施
True CES therapy
The participant will be trained in device usage and instructed to use the device each evening around the same time for 60 minutes (timer will be pre-set). The intervention (true CES) will occur over the course of 6 weeks.
干预措施: Cranial electrical/electrotherapy stimulation (CES) (Device)
Sham CES therapy
The participant will be trained in device usage and instructed to use the device each evening around the same time for 60 minutes (timer will be pre-set). The intervention (sham CES) will occur over the course of 6 weeks.
干预措施: Sham Cranial electrical/electrotherapy stimulation (CES) (Device)
True CES therapy for non-responders
For the non-responders (<2 point decrease on DVPRS), the blind will be broken, and those non-responder participants who were initially assigned to sham placebo CES during the first 6 weeks of the intervention, now will be offered the opportunity to utilize the true CES device in a modified sequential parallel comparison design for an additional 6 weeks.
干预措施: Cranial electrical/electrotherapy stimulation (CES) (Device)
结局指标
主要结局
Change in Defense and Veterans Pain Rating Scale (DVPRS) from baseline
时间窗: Baseline, 6 and 12 weeks post-intervention
The Defense and Veterans Pain Rating Scale (DVPRS) is a pain assessment tool. Patients will rate their pain intensity on a scale of 0 to 10, where 0 is no pain and 10 is the worst imaginable pain.
Change in Brief Pain Inventory (BPI) severity subscale from baseline
时间窗: Baseline, 6 and 12 weeks post-intervention
The BPI assesses pain severity and interference with function. The pain severity subscale consists of 4 items, each rated on a 0-10 numerical scale (0 = "no pain," 10 = "pain as bad as you can imagine"). Scores are averaged to yield a total range of 0-10. Lower scores reflect less severe pain and are considered favorable outcomes.
Change in Brief Pain Inventory (BPI) pain interference subscale from baseline
时间窗: Baseline, 6 and 12 weeks post-intervention
The pain interference subscale consists of 7 items rated on a 0-10 numerical scale (0 = "does not interfere," 10 = "completely interferes"), assessing the impact of pain on daily activities such as mood, walking ability, work, and enjoyment of life. Scores are averaged to create a total range of 0-10. Lower scores reflect less interference from pain and are considered favorable outcomes.
次要结局
- Change in sit-to-stand/chair stand test(Baseline, 6 and 12 weeks post-intervention)
- Change in bicep(arm) curls(Baseline, 6 and 12 weeks post-intervention)
- Change in handgrip strength(Baseline, 6 and 12 weeks post-intervention)
- Change in finger-tap test(Baseline, 6 and 12 weeks post-intervention)
- Change in Patient-Reported Outcomes Measurement Information System (PROMIS): sleep score(Baseline, 6 and 12 weeks post-intervention)
- Change in PROMIS: social isolation score(Baseline, 6 and 12 weeks post-intervention)
- Change in PROMIS: alcohol use score(Baseline, 6 and 12 weeks post-intervention)
- Change in PROMIS: global health score(Baseline, 6 and 12 weeks post-intervention)
- Change in PROMIS 29 score(Baseline, 6 and 12 weeks post-intervention)
- Change in SF-36 score from baseline(Baseline, 6 and 12 weeks post-intervention)
- Change in Resting-State fMRI Connectivity measured with Seed-Based Functional Connectivity Analysis(Baseline, 6 and 12 weeks post-intervention)
- Change in Resting-State fMRI Connectivity measured with Independent Components Analysis(Baseline, 6 and 12 weeks post-intervention)
- Change in Magnetic Resonance Spectroscopy Metabolite: lactate(Baseline, 6 and 12 weeks post-intervention)
- Change in Magnetic Resonance Spectroscopy Metabolite: N-acetyl aspartate (NAA)(Baseline, 6 and 12 weeks post-intervention)
- Change in Magnetic Resonance Spectroscopy Metabolite: choline(Baseline, 6 and 12 weeks post-intervention)
- Change in Magnetic Resonance Spectroscopy Metabolite: tCr(Baseline, 6 and 12 weeks post-intervention)
- Change in Magnetic Resonance Spectroscopy Metabolites: Ratio of NAA/tCr(Baseline, 6 and 12 weeks post-intervention)
研究者
Anna Woodbury
Associate Professor
Emory University