Transcranial, Light-Emitting Diode (LED) Therapy to Improve Cognition in GWVI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 4
- 主要终点
- ROCFT, Delayed Recall
研究概览
简要总结
The purpose of this study is to learn if an experimental treatment can help thinking ability, and memory in Veterans with Gulf War Veterans Illnesses (GWVI). The experimental treatment uses light-emitting diodes (LEDs), that are applied outside the skull, to the head using a helmet that is lined with near-infrared diodes. LEDs are also placed in the nostrils (one red diode; and one near-infrared diode), near-infrared photons to the olfactory bulbs located on the orbito-frontal cortex. There are connections between the olfactory bulbs and the hippocampus. A treatment takes about 30 minutes. The participants receive a series of LED treatments which take place as outpatient visits at the VA Boston Healthcare System, Jamaica Plain Campus. The FDA considers the helmet LED device used here, to be a non-significant risk device. The diodes in the device placed in the nose are low-risk devices, within the FDA Category of General Wellness. In addition, a single, 90 mW near-infrared (NIR) LED was placed on each ear. The LEDs do not produce heat.
详细描述
Rationale:
Impaired cognition is one of the 3 major symptom areas of GWVI. Mitochondrial dysfunction is reported in Gulf War Illness (GWI) veterans, associated with neurotoxicant exposures during deployment - e.g., organophosphate pesticides (OP); and pretreatment nerve agents, pyridostigmine bromide (PB) pills.
Improved mitochondrial function with increased production of adenosine tri-phosphate (ATP) has been reported in hypoxic/compromised cells treated with red/NIR photons.
Recent studies in humans have shown an increase in regional cerebral blood flow subjacent to where the near-infrared LEDs were placed on the scalp (Schiffer et al., 2009; Nawashiro et al., 2012; Chao L.L., 2019).
General Explanation of the Light-Emitting Diode Treatment Procedure:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The participant and the person administering treatments wore goggles (LS-DIO, Phillips Safety Products, Inc.) that blocked 600-900nm wavelengths including red 633 nm wavelength, emitted from the red Intranasal diode. All participants were randomly assigned by computer to Group 1 (Sham First) or Group 2 (Real First) in blocks of 10.
入排标准
- 年龄范围
- 38 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants were recruited from the participants in a Department of Defense (DoD) study of a longitudinal cohort of Gulf War Veterans who returned from their deployment in 1991 through Ft. Devens, MA. This cohort has been followed at multiple time points since the end of war (Proctor et al., 1998), and through the VA Informatics and Computing Infrastructure (VINCI)/Corporate Data Warehouse (CDW) database, with approval from NDS. The San Francisco VA Medical Center (SF VAMC) was a second site on the study (35 Veterans were run in Boston; 12 were run in San Francisco on the same protocol.)
- •Those recruited from the VINCI/CDW database, resided within a 25 mile radius of the Boston VA Healthcare System (VABHS) or 25 miles of the SF VA Medical Center (VAMC). The Institutional Review Board at the VA BHS and the SF VAMC (University of California, San Francisco) approved the study. In accordance with the Declaration of Helsinki, Informed Consent and HIPAA authorization was obtained from all participants.
- •Participants answered 'Yes' to the following questions: 1) Difficulty concentrating; and/or 2) Difficulty remembering recent information.
- •Must be a Veteran deployed in 1990-1991 Gulf War, in the Kuwait Theatre
- •Meets criteria for GWVI as defined by "Symptom Questions used to identify Gulf War Illness by Kansas Case Definition, and Chronic Multisymptom Illness by Fukuda Case Definition" (Steele, 2000; Fukuda et al., 1998). Participants must have the presence of 1 or more chronic symptoms (lasting >6 months) from at least 2 of 3 symptom categories from Fukuda et al., (1998): 1) musculoskeletal (muscle pain, or joint pain, stiffness); 2) mood-cognition 3) fatigue.
- •Ages 38 - 65 years
- •Must be physically able to travel to the VA Boston Healthcare System, Jamaica Plain or San Francisco VA Medical Center, for Neuropsychological testing and transcranial LED treatments
- •Must meet screening criteria from the Eligibility Screening:
- •The following Neuropsychological (NP) tests were administered at Screening: Trail Making Test A & B (Reynolds, 2002); Controlled Oral Word Association Test (COWAT (FAS); Spreen & Benton, 1977; Benton and Hamsher, 1989); California Verbal Learning Test - II (Delis et al., 2000); Color-Word Interference Test (Stroop; Delis, Kaplan, Kramer, 2001). Additional screening tests included: Short Form McGill Pain Questionnaire (Melzac, 1984); Overall VAS current pain rating (0-10); and the PTSD Checklist- Civilian (PCL-C, Weathers et al., 1994).
- •Participants were required to score at least 2 SD below the standardized norm (age, education, gender) on at least 1 NP screening test or 1 SD below the standardized norm on at least 2 NP screening tests. The Word Reading Subtest from the Wide Range Achievement Test-4 (Wilkinson and Robertson, 2006) was used to estimate premorbid level of cognitive functioning. The SD for each participant on each NP screening test was adjusted by his/her estimated premorbid cognitive level.
- •The Test of Memory Malingering (TOMM, 1996) was administered. Participants who failed Trial 2, or Trial 1 and 2 were excluded from the study. If a participant failed Trial 1, but did not fail Trial 2, he/she was not excluded if he/she showed evidence of poor learning on other NP screening tests such as the CVLT (Schroeder et al., 2013, Arch Clin Neuropsych) Participants were required to have a level of pain 7/10 or less on the VAS and less than 38/50 on the McGill pain questionnaires at screening, as pain has been shown to influence cognition (Moriarty et al., 2011, Review).
排除标准
- •Presence of a neurodegenerative disease such as ALS, Parkinson's, Dementia
- •Presence of a life-threatening disease such as cancer
- •Presence of a severe mental disorder such as schizophrenia, or bipolar depression (not associated with PTSD)
- •Current substance abuse or active treatment within last 6 months
结局指标
主要结局
ROCFT, Delayed Recall
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Rey Osterrieth Complex Figure Test (ROCFT); Delayed (20-min) Recall measures Visuospatial memory with min 0 and max 36; higher = better outcome Participant is asked to draw the figure from memory after a 20 minute delay (other tasks completed during this time). Figure has 18 units; Scoring is based on accuracy and placement: 0 if unrecognizable or omitted, .5 recognizable, 1 either accurate or correctly placed or 2 both accurate and correctly placed, per unit.
Trails Condition 4
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Delis-Kaplan Executive Function (DEKFS) Trails 4; Number-Letter Switching; measures Attention/Executive Function Reaction Time lower is better Connect numbers and letters, alternating between numbers and letters. (1-A-2-B...) as quickly as possible. Ends at P.
Trails Condition 2
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Delis-Kaplan Executive Function (DKEFS) Trails 2; Number Sequencing; measures Attention/Executive Function Reaction Time with lower = better outcome Connect the numbers in consecutive order from 1 to 16, as quickly as possible.
Stroop Inhibition (Trial 3)
时间窗: Within 1-2 weeks before LED treatment series, within 1 week and 1 month after LED treatment series
Color-Word Interference Test Trial 3; measures Attention/Executive Function; inhibition Reaction Time lower = better outcome Name the color ink each word is printed in for a series of words, as quickly as possible.
California Verbal Learning Test -II (CVLT-II) Total Trials 1-5
时间窗: within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment
CVLT-II Total Trials 1-5, measures Learning/Memory over 5 consecutive trials; with a min score of 0 and a max score of 80; higher score = better outcome Participant must immediately recall words from a 16 word list A read aloud by the examiner. The same list is presented for each of the 5 trials. Total across 5 trials is scored.
Digit Span Total Forward + Backwards
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Total (Forwards+Backwards); measures Attention/Executive Function; working memory with a min score of 0 and a max score of 28; higher score = better outcome
Digit Span Forwards
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Repeat a series of numbers, exactly as spoken, in the same order. Starts with 2 digits and continues to 7 digits in a row. Participant is given 2 attempts at each level. If 0/2 attempts are correct for a given level, testing is discontinued. Scoring: 2 points both trials per set; 1 point 1 trial; 0 points failed both trials Forwards; measures Attention/Executive Function with a min score of 0 and a max score of 14; higher score = better outcome
Digit Span Backwards
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Repeat a series of numbers, in reverse order. Starts with 2 digits and continues to 7 digits in a row. Participant is given 2 attempts at each level. If 0/2 attempts are correct for a given level, the test is discontinued. Scoring: 2 points both trials correct for each set; 1point 1 trial correct; 0 points no trials Backwards; measures Attention/Executive Function with a min score of 0 and a max score of 14; higher score = better outcome
CVLT-II, Short Delay Cued Recall
时间窗: within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment
California Verbal Learning Test -II, Short Delay Cued Recall, measures Learning/Memory; with a min score of 0 and a max score of 16; higher score = better outcome Participants are now asked to recall items from list A again, but are given cues by category. (4 categories, 4 items each). Total is score across all 4 categories.
CVLT-II Long Delay Free Recall
时间窗: within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment
California Verbal Learning Test- II, Long Delay (20 min) Free Recall, measures Memory with a min score of 0 and a max score of 16; higher score = better outcome After a 20 minute delay (other tasks run during this delay), participant is asked to recall items from List A. Total is number of words recalled.
Conner's Continuous Performance Test II (CPT) False Alarms
时间窗: within 1 week before LED treatment series, within 1 Week and 1 Month after the last LED treatment
CPT; False Alarms (Administered on laptop computer) measures Selective and Sustained Attention percent errors; lower = better outcome Participant presses space bar when an X appears on screen. False alarms is number of errors made (responding to non-targets), reported as percentage.
Stroop Inhibition/Switching
时间窗: Within 1-2 weeks before LED treatment series, within 1 week and 1 month after LED treatment series
Color-Word Interference Test Trial 4 (Inhibition/Switching); measures Attention/Executive Function Reaction Time lower = better outcome Participants must sometimes name the color ink in which the word (color) is printed or, if there is a box around the word, they must read the word.
Conner's Continuous Performance Test II (CPT), D'
时间窗: within 1 week before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Conner's Continuous Performance Test II (CPT); D' (sensitivity index) (Administered on laptop computer) measures Selective and Sustained Attention; ability to detect the signal (x) within noise; values range -2 to 2; higher value better Value d' is a measure of the difference between the signal (X) and noise (non-target letters) distributions, assessing the participant's discriminative power.
Rey Osterrieth Complex Figure Test (ROCFT); Immediate Recall
时间窗: within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment
ROCFT; Immediate Recall measures Visuospatial memory with min 0 and max 36; higher score better outcome Participant is presented with a figure. They are asked to copy the figure. Then they are immediately asked to recall and draw the figure. Figure is scored on 18 units; up to 2 points per unit Scoring based on accuracy and placement of figure parts: A score of 0, 0.5 recognizable and incorrectly placed, 1 accurate or correctly placed or 2 both accurate and correctly placed; 0 is given if part is omitted or unrecognizable.
CVLT-II, Short Delay Free Recall
时间窗: within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment
California Verbal Learning Test -II, Short Delay Free Recall, measures Memory; with min score of 0 and a max score of 16; higher score = better outcome A second list B is presented for one trial of recall before asking participants to recall items from the first list A. Number of items recalled from list A is scored.
CPT Correct Detections, Reaction Time (RT)
时间窗: within 1 week before LED treatment series, within 1 Week and 1 Month after the last LED treatment
Conner's Continuous Performance Test II; Mean Correct Detections, Reaction Time, (Administered on laptop computer) measures Selective and Sustained Attention; shorter = better outcome Participant must press the space bar when they see an X. Reaction Time for correct responses only.
CVLT-II Long Delay Cued Recall
时间窗: within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment
California Verbal Learning Test- II, Long Delay (20 min) Cued Recall measures Memory; with a min score of 0 and a max score of 16; higher score = better outcome After 20 minute delay participant is given cues (4 categories) and asked to recall the words within each category. Total number of items recalled across all categories.
次要结局
- Multidimensional Fatigue Inventory, Physical Score(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Visual Analog Pain Rating(within 1-2 weeks of LED treatment, within 1 Week and 1 Month after the last LED treatment)
- Short Form McGill Pain Questionnaire(within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Short Form-36V Plus (MCS)(within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment)
- Beck Depression Inventory (BDI)(within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Karolinska Sleepiness Scale(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Multidimensional Fatigue Inventory (MFI), General Score(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- PCL-Civilian Survey(within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Pittsburgh Sleep Quality Index (PSQI)(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Short Form-36V Plus (PCS)(within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment)
- Multidimensional Fatigue Inventory, Reduced Activity Score(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Multidimensional Fatigue Inventory, Reduced Motivation Activity(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)
- Multidimensional Fatigue Inventory, Mental Fatigue(1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment)