Scalp Application of LED Therapy to Improve Thinking and Memory in Veterans With Gulf War Illness

NCT01782378 | Completed Results DMC

• 2 other identifiers: SPLD-014-12S1I01CX000524-01A1
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Gulf War Veterans Illness; Neurobehavioral Manifestations; Memory Disorders

Keywords

Gulf War Veterans Illness; Veterans Health; Executive Function; Memory; Attention; Cognition; Laser Therapy, Low-Level; Phototherapy; Light Therapy; Depression; Light-Emitting Diodes

Outcome Measures

Primary Outcomes (17)

• Digit Span Forwards

  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

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Digit Span Backwards

  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

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Digit Span Total Forward + Backwards

  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

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Trails Condition 2

  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.

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Trails Condition 4

  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.

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Stroop Inhibition (Trial 3)

  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.

  Within 1-2 weeks before LED treatment series, within 1 week and 1 month after LED treatment series

• Stroop Inhibition/Switching

  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.

  Within 1-2 weeks before LED treatment series, within 1 week and 1 month after LED treatment series

• California Verbal Learning Test -II (CVLT-II) Total Trials 1-5

  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.

  within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment

• CVLT-II, Short Delay Free Recall

  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.

  within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment

• CVLT-II, Short Delay Cued Recall

  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.

  within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment

• CVLT-II Long Delay Free Recall

  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.

  within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment

• CVLT-II Long Delay Cued Recall

  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.

  within 1-2 weeks before LED treatment series; within 1 Week and 1 Month after the last LED treatment

• Conner's Continuous Performance Test II (CPT) False Alarms

  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.

  within 1 week before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• CPT Correct Detections, Reaction Time (RT)

  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.

  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'

  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.

  within 1 week before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• Rey Osterrieth Complex Figure Test (ROCFT); Immediate Recall

  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.

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

• ROCFT, Delayed Recall

  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.

  within 1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

Secondary Outcomes (13)

• Beck Depression Inventory (BDI)

  within 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

• 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

• Pittsburgh Sleep Quality Index (PSQI)

  1-2 weeks before LED treatment series, within 1 Week and 1 Month after the last LED treatment

Study Arms (2)

Real LED Treatment Series

ACTIVE COMPARATOR

Participants in this group receive a series of 15 real LED treatments with the helmet and intranasal devices: Transcranial NIR, 830nm LED Helmet and two intranasal nose clips (633 nm, and 810 nm, Vielight, Inc., Toronto), 28-minute treatment, 2 days/ week, 7.5 weeks, at least 48 hours between treatments. Additionally, two NIR 870nm LED cluster heads (MedX Health, Toronto) were placed over the L and R ears during the last 4 minutes of the treatment session. LEDs are FDA-cleared, non-significant risk. Both the participant and the person performing the treatment wore goggles that block red wavelength (from the red intranasal). Real or Sham LED devices look and feel identical.

Device: Real LED Treatment

Sham LED Treatment Series

SHAM COMPARATOR

Participants in this group first receive a series of 15 sham LED treatments with the helmet and intranasal devices containing sham LEDs (no photons were emitted): Transcranial LED Helmet and two intranasal nose clips (sham LEDs, Vielight, Inc., Toronto), 28-minute treatment, 2 days/ week, 7.5 weeks, at least 48 hours between treatments. Additionally, two sham LED cluster heads (MedX Health, Toronto) were placed over the L and R ears during the last 4 minutes of the treatment session. These participants were offered an optional Second Real Series of identical 15 real LED treatments. Both the participant and the person performing the treatment wore goggles that block red wavelength (from the red intranasal). Real or Sham LED devices look and feel identical.

Device: Real LED Treatment; Device: Sham LED Treatment

Interventions

Real LED Treatment DEVICE

PhotoMedex Helmet: 12 Pods, 4.5 x 4.8cm (21.6 cm2); 20 diodes; 830nm; Power Output (PO) 665.3 mW; Power Density (PD)/LED 30.8 mW/cm2; CW; Time/session 28m 10s\*; Dose: Energy Density 26 J/cm2. MedX Device: 1 Cluster Head/ear, 2 inch diameter (22.48 cm2); 870nm; PO 90 mW; PD/LED 4 mW/cm2; CW; Time/session 4m; Energy Density 4 J/cm2; 2 Vielight Intranasal Devices: Red, 633nm diode; PO 6.5 mW; PD/LED 7.6 mW/cm2; CW; Time/session 25m; Energy Density 11.4 J/cm2 and NIR, 810nm diode; PO 6.5 mW; PD/LED 7.6 mW/cm2; Pulse frequency 10Hz; Duty Cycle 50%; Time/session 25m; Energy Density 11.4 J/cm2 Thor Photomedicine Helmet: 10 Pods, 6cm diameter (28.3 cm2); 35 diodes; Wavelength 850nm; PO 1050 mW; PD/LED 50 mW/cm2; CW; Time/session 23m, 24s; Energy Density 26 J/cm2 2 Placement sets: 1) midline, 6 cluster heads; 2) L\&R side of head 12 cluster heads (14m, 5s, each set); 1) midline, 5 cluster heads; 2) L\&R side of head 10 cluster heads (11m, 42s, each set) CW, Continuous Wave

Also known as: Photomedex Helmet, Thor Photomedicine Helmet, MedX LED cluster heads, Vielight Intranasal

Real LED Treatment Series; Sham LED Treatment Series

Sham LED Treatment DEVICE

Intervention for Real and Sham are Identical, but sham has power output of 0, no photons emitted.

Sham LED Treatment Series

Eligibility Criteria

• Age: 38 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, 94121, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130, United States

Location

Related Publications (1)

• Martin PI, Chao L, Krengel MH, Ho MD, Yee M, Lew R, Knight J, Hamblin MR, Naeser MA. Transcranial Photobiomodulation to Improve Cognition in Gulf War Illness. Front Neurol. 2021 Jan 21;11:574386. doi: 10.3389/fneur.2020.574386. eCollection 2020.

  PMID: 33551948 DERIVED

MeSH Terms

Conditions

Neurobehavioral Manifestations; Memory Disorders; Depression

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Limitations and Caveats

Small sample size, missing data, heterogeneity at entry on each test among subjects, government shutdown 1st Yr, 2013, delayed VA contracting to order Helmets. Helmets defective 2014, re-designed. Newer LED devices, may allow home treatment.

Results Point of Contact

• Title: Margaret Naeser, PhD
• Organization: VA Boston Healthcare System, Jamaica Plain Campus, Boston, MA

Margaret.Naeser@va.gov; mnaeser@bu.edu

857-364-4030

Study Officials

• Margaret Naeser, PhD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

• Linda L Chao, PhD

  San Francisco VA Medical Center, San Francisco, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This was a blinded, randomized, sham-controlled partial crossover study, with 2 Groups. Group 1: Sham LED Series First followed by optional Real LED Series Second. Group 2: One Real LED Series, only. Neuropsychological (NP) tests were completed at Entry (T1), within 1 week post- (T2) and at 1 month post- the 15th treatment (T3) (First series). NP testing was administered after the optional Second Real Series within 1 week post- (T4) and at 1 month post- the 15th treatment (T5). Primary Outcome Measures included NP tests in 3 domains: 1) Attention/Executive Function; 2) Learning and Memory; 3) Psychomotor/Visual Spatial. The Secondary Outcome Measures included sleep, pain, fatigue, and mood.

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: January 9, 2015
• Primary Completion: August 6, 2018
• Study Completion: August 6, 2018
• Last Updated: January 22, 2020
• Results First Posted: January 22, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)