Moderate Traumatic Brain Injury (TBI)
Conditions
Keywords
Traumatic brain injury, TBI, Low-level light therapy, LLLT, LLLT helmet
Brief summary
The purpose of this research study is to find out if a specialized helmet that provides low levels of near infrared light, also known as low-level light therapy (LLLT) has any effect on the recovery of people who have recently (within 72h) suffered a moderate traumatic brain injury (TBI).
Detailed description
The specific aim of this pilot study is to determine the feasibility of using the LLLT helmet in patients with moderate TBI and to quantify the response to LLLT using magnetic resonance (MR) and clinical outcome measures. We hypothesize that we will be able to quantify the response to LLLT through MR imaging and clinical outcome measures.
Interventions
DEVICEActive LLLT helmet application
LED helmet applied with light activated
DEVICENon-active LLLT helmet application
LED helmet applied without light activated
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old; * Injury within 72 hours at the time of consent; * Head injury requiring hospital admission; * A Glasgow Coma Scale (GCS) score of 9-12 or 13-15 with abnormal imaging.
Exclusion criteria
* Need for emergency neurosurgical intervention (including placement of intracranial pressure monitoring devices or drainage catheters); * Hemodynamic instability as determined by the clinician; * History of any of the following: (i) brain tumor; (ii) prior TBI occurring within the past year and requiring hospital admission; (iii) a new diagnosis within the past year of either stroke or epilepsy; (iv) an established diagnosis of any of the following neurodegenerative diseases: Alzheimer's, Picks, Parkinson's, Lewy body dementia, Huntington's, amytropic lateral sclerosis, spinocerebellar ataxia, vascular dementia, HIZ-associated dementia, dementia due to metabolic causes (Addison, Cushing, hypothyroidism, renal failure, prophyrias, Wilson, mitochondrial diseases, Wernicke-Korsakoff syndrome, and dementia of unknown etiology. * Pregnancy (all women of child-bearing age will need to have a negative pregnancy test prior to the start of the interventional portion of the study); * Electrical implants such as cardiac pacemakers or perfusion pumps; * Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants, or any other contra-indications to MRI. * Clinical determination that subject cannot undergo MRI * Breastfeeding * Unstable cervical fractures * Scalp lacerations or surgical wounds severe enough to preclude safe application of device * Unreliable to follow up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Feasibility of Applying Light Therapy After Moderate TBI | up to seven days after enrollment | Number of subjects to successfully complete light therapy without serious unanticipated adverse events related to application of the device. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | up to 3 months after treatment | The presence of chronic white matter disease was evaluated using Fazekas scale. The scale divides the white matter in periventricular and deep white matter, and each region is given a grade depending on the size and confluence of lesions. periventricular white matter (PVWM). 0 = absent 1. = caps or pencil-thin lining 2. = smooth halo 3. = irregular periventricular signal extending into the deep white matter A neuroradiologist evaluated the 3D T2-SPACE-FLAIR images to detect the presence of T2 hyperintensities and their degree (0: absent; 1: mild; 2: moderate; and 3: severe) for PVWM. Higher values represent a worse outcome. |
| Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | up to 3 months after treatment | The presence of chronic white matter disease was evaluated using Fazekas scale. The scale divides the white matter in periventricular and deep white matter, and each region is given a grade depending on the size and confluence of lesions. deep white matter (DWM) 0 = absent 1. = punctate foci 2. = beginning confluence 3. = large confluent areas A neuroradiologist evaluated the 3D T2-SPACE-FLAIR images to detect the presence of T2 hyperintensities and their degree (0: absent; 1: mild; 2: moderate; and 3: severe) for DWM. Higher values represent a worse outcome. |
| Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ scores were collected at approx 72 hours, 14 days, 3 months, and 6 months and the mean was calculated for the values reported. | RPQ is a 16 item self-assessment questionnaire completed via an in-person or phone interview. Each item in the questionnaire is assessed on a 5-point scale ranging from 0 (no problem) - 4 (severe problem). The questions are grouped in two non-overlapping sets: the RPQ-3 includes early, objective, physical symptoms, and the RPQ-13 group includes later, more cognitive and behavioral symptoms. The RPQ-3 encompasses headache, dizziness, and nausea/vomiting. The RPQ-13 includes questions evaluating noise sensitivity, sleep disturbance, fatigue, irritability, depressed mood, forgetfulness, poor concentration, longer thinking time, blurred vision, light sensitivity, double vision, and restlessness. The RPQ-3 ranges from 0 - 12 (best to worst) and RPQ-13 ranges from 0 - 52 (best to worst). RPQ Total is the theoretical max/min RPQ score with a combined possible score ranging from 0-64 (best to worst). The outcome measures are |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Non-active LLLT Helmet Application A helmet containing near infrared LED's (LLLT helmet) will be applied to the head, however, the LEDs will not be turned on / activated.
Non-active LLLT helmet application: LED helmet applied without light activated | 24 |
| Active LLLT Helmet Application A helmet containing near infrared LEDs (LLLT helmet) will be applied and the LEDs will be turned on/activated
Active LLLT helmet application: LED helmet applied with light activated | 19 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 9 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Active LLLT Helmet Application | Total | Non-active LLLT Helmet Application |
|---|---|---|---|
| Age, Continuous | 46.05 years STANDARD_DEVIATION 19.93 | 50.49 years STANDARD_DEVIATION 17.44 | 54.00 years STANDARD_DEVIATION 14.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 9 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 32 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Injury Mechanism Bike/Motorcycle Accident with Helmet | 0 Participants | 4 Participants | 4 Participants |
| Injury Mechanism Bike/Motorcycle Accident without Helmet | 1 Participants | 1 Participants | 0 Participants |
| Injury Mechanism Fall | 11 Participants | 25 Participants | 14 Participants |
| Injury Mechanism Other | 0 Participants | 1 Participants | 1 Participants |
| Injury Mechanism Pedestrian accident with car/motorcycle/bike | 1 Participants | 4 Participants | 3 Participants |
| Injury Mechanism Restrained Automobile Accident | 3 Participants | 3 Participants | 0 Participants |
| Injury Mechanism Unrestrained Automobile Accident | 0 Participants | 1 Participants | 1 Participants |
| Injury Mechanism Violence/assault | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 15 Participants | 33 Participants | 18 Participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 28 |
| other Total, other adverse events | 20 / 31 | 13 / 28 |
| serious Total, serious adverse events | 7 / 31 | 4 / 28 |
Outcome results
Primary
Safety and Feasibility of Applying Light Therapy After Moderate TBI
Number of subjects to successfully complete light therapy without serious unanticipated adverse events related to application of the device.
Time frame: up to seven days after enrollment
Population: Subjects who completed light or sham treatment and at least one MRI scan. 43 patients completed the study with at least one MRI scan, 19 subjects in the Light treatment group and 24 subjects in the sham treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-active LLLT Helmet Application | Safety and Feasibility of Applying Light Therapy After Moderate TBI | 24 Participants |
| Active LLLT Helmet Application | Safety and Feasibility of Applying Light Therapy After Moderate TBI | 19 Participants |
Secondary
Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM)
The presence of chronic white matter disease was evaluated using Fazekas scale. The scale divides the white matter in periventricular and deep white matter, and each region is given a grade depending on the size and confluence of lesions. deep white matter (DWM) 0 = absent 1. = punctate foci 2. = beginning confluence 3. = large confluent areas A neuroradiologist evaluated the 3D T2-SPACE-FLAIR images to detect the presence of T2 hyperintensities and their degree (0: absent; 1: mild; 2: moderate; and 3: severe) for DWM. Higher values represent a worse outcome.
Time frame: up to 3 months after treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Absent(0)/Puctuate foci(1) | 19 Participants |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Beginning confluence (2) | 3 Participants |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Large confluent areas | 1 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Absent(0)/Puctuate foci(1) | 16 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Beginning confluence (2) | 3 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Deep White Matter (DWM) | DWM: Large confluent areas | 0 Participants |
Secondary
Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM)
The presence of chronic white matter disease was evaluated using Fazekas scale. The scale divides the white matter in periventricular and deep white matter, and each region is given a grade depending on the size and confluence of lesions. periventricular white matter (PVWM). 0 = absent 1. = caps or pencil-thin lining 2. = smooth halo 3. = irregular periventricular signal extending into the deep white matter A neuroradiologist evaluated the 3D T2-SPACE-FLAIR images to detect the presence of T2 hyperintensities and their degree (0: absent; 1: mild; 2: moderate; and 3: severe) for PVWM. Higher values represent a worse outcome.
Time frame: up to 3 months after treatment
Population: Of the 68 patients that were randomized, 28 completed at least one light therapy session. 43 patients completed the study with at least one MRI scan. 19 subjects in the light treatment group and 24 subjects in the sham treatment group. One MRI was deemed low quality and excluded from analysis (19 light treatment / 23 sham)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Absent / Caps or pencil-thin lining (1) | 19 Participants |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Smooth halo (2) | 3 Participants |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Irregular periventricular signal (3) | 1 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Absent / Caps or pencil-thin lining (1) | 18 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Smooth halo (2) | 1 Participants |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on MRI Using the Fazekas Scale for Periventricular White Matter (PVWM) | PVWM: Irregular periventricular signal (3) | 0 Participants |
Secondary
Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function
RPQ is a 16 item self-assessment questionnaire completed via an in-person or phone interview. Each item in the questionnaire is assessed on a 5-point scale ranging from 0 (no problem) - 4 (severe problem). The questions are grouped in two non-overlapping sets: the RPQ-3 includes early, objective, physical symptoms, and the RPQ-13 group includes later, more cognitive and behavioral symptoms. The RPQ-3 encompasses headache, dizziness, and nausea/vomiting. The RPQ-13 includes questions evaluating noise sensitivity, sleep disturbance, fatigue, irritability, depressed mood, forgetfulness, poor concentration, longer thinking time, blurred vision, light sensitivity, double vision, and restlessness. The RPQ-3 ranges from 0 - 12 (best to worst) and RPQ-13 ranges from 0 - 52 (best to worst). RPQ Total is the theoretical max/min RPQ score with a combined possible score ranging from 0-64 (best to worst). The outcome measures are
Time frame: RPQ scores were collected at approx 72 hours, 14 days, 3 months, and 6 months and the mean was calculated for the values reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-3 | 4.55 score on a scale | Standard Deviation 3.13 |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-Total | 17.18 score on a scale | Standard Deviation 10.01 |
| Non-active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-13 | 12.64 score on a scale | Standard Deviation 7.83 |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-3 | 3.94 score on a scale | Standard Deviation 3.19 |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-13 | 10.94 score on a scale | Standard Deviation 9.98 |
| Active LLLT Helmet Application | Neuroreactivity of Light Therapy to the Injured Brain Based on Neurcognitive Function | RPQ-Total | 14.88 score on a scale | Standard Deviation 12.08 |