- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02383472
LED Therapy for the Treatment of Concussive Brain Injury
Transcranial LED Therapy for the Treatment of Chronic Mild Traumatic Brain Injury
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Concussion, also known as mild traumatic brain injury (mTBI), results from a rotational acceleration of the brain. The biomechanical forces which cause concussion lead to the opening of ion channels within the neuronal cell membranes, allowing for a massive influx of sodium and efflux of potassium. This results in a spreading depression type of phenomenon, leading to the depolarization of neurons diffusely throughout the brain.19 In order to restore the homeostatic ion gradients across the membrane, the sodium-potassium pumps require increasing amounts of adenosine triphosphate (ATP). Thus, there is an increased need for ATP after concussion. ATP is supplied by the glycolysis of glucose from the blood stream. Both experimental models of concussion and human studies, however, show decreased cerebral blood flow after the initial response to injury. Thus, there is an increased demand for ATP after concussion; but a diminished supply of glucose to meet the demand.
The absorption of light in the red/near infrared wavelength spectrum by cytochrome C oxidase increases ATP synthesis. Thus, by increasing ATP synthesis, red/near infrared LEDs can treat the underlying pathophysiological cause of concussion symptoms. If successful, this would be the first therapy to directly treat the underlying pathophysiology of concussion.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Boston Children's Hospital
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Waltham, Massachusetts, United States, 02453
- Boston Children's Hospital at Waltham
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients 11 years old or greater
- Diagnosed with a concussion whose symptoms have persisted for more than 4 weeks
- Total score on the cognitive components of the post-concussion symptom scale exceeds 9, or if they have a composite score on any one of the 4 main outputs of the computerized neurocognitive assessment: Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) that is below the 90th percentile for their age.
Exclusion Criteria:
- Clinically indicated imaging has been obtained where a hemorrhage is demonstrated
- Being considered for an alternate diagnosis (other than concussion)
- Have a pre-injury diagnosis of any of the following: depression, post-traumatic stress disorder, other psychiatric disorder
- Taking any of the following medications: amantadine, , amphetamine, atomoxetine
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MedX Health Console model 1100
The treatment group will receive LED treatments over 6 weeks, 3 times per week, totaling 18 visits.
All treatments will take place at Boston Children's Hospital.
The cluster heads are applied to frontal, parietal, and temporal areas.
Each cluster head is applied to the forehead/scalp areas for up to 10 minutes.
There will be two 10-minute LED/placebo treatment periods per visit, each with different cluster head placements on the head/scalp.
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All treatments will be administered using the MedX Health Console model 1100.
These units were cleared by the FDA as non-significant risk in 2003 and approved for home treatment use in 2005 "for temporary increase in local blood flow circulation . . .
for temporary relief of minor muscle and joint aches."
Cluster heads are 2 inches in diameter.
Each contains 9 red (633nm wavelength) diodes and 52 near infrared (870 nm wavelength) diodes.
LED cluster heads would be applied to the frontal, parietal and temporal areas, as well as the mid sagittal suture line
Other Names:
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Placebo Comparator: MedX Health Console model 1100-placebo
Subjects enrolled in the placebo group will be on the same schedule as the treatment group.
The placebo group will receive LED placebo over 6 weeks, 3 times per week, totaling 18 visits.
All placebo patients will take place at Boston Children's Hospital.
The cluster heads are applied to frontal, parietal, and temporal areas.
Each cluster head is applied to the forehead/scalp areas for up to 10 minutes.
There will be two 10-minute LED/placebo treatment periods per visit, each with different cluster head placements on the head/scalp.
|
The placebo machine is identical in appearance as the treatment machine; It vibrates, warms, and does everything the treatment machine does except it does not have LED lights on the marker, therefore it cannot emit light.
Subjects enrolled in the placebo group will be on the same schedule as the treatment group.
They will have two, 10 minute treatments, three times a week totaling 18 visits.
The placebo allows the researchers to isolate the effect of the study treatment.
If patient's in the LED treatment group fare significantly better than those in the placebo treatment group, the study helps support the conclusion that the LED therapy is effective.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Difference in Change in Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Score at Baseline and 6 Weeks.
Time Frame: From baseline to 6 weeks
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The primary outcome is mean difference on composite scores of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) between entry into the study and completion of treatment (visit 18, week 6) for both the LED group and the placebo group.
The mean difference is calculated by taking the mean of differences of the entry scores minus the 6 week scores.
There are 5 composite scores on the ImPACT test; verbal memory, visual memory, visual motor speed, reaction time, and symptom score.
The ranges for these subscales are as follows: verbal memory and visual memory: 0-100, visual motor speed: 0-60, reaction time: 0-1.0, and symptom score: 0-132.
A higher verbal memory, visual memory, and visual motor speed represent a better outcome, while a lower reaction time and lower symptom score represent a better outcome.
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From baseline to 6 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Difference in Change in Delis-Kaplan Executive Function System (D-KEF) Color-Word Interference and Trail Making Test Performance at Weeks 3 and 6.
Time Frame: From baseline to 3 weeks and from baseline to 6 weeks
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This measure indicates the mean differences in Delis-Kaplan Executive Function System (D-KEF) tests between entry into the study and 3 weeks and entry into the study and 6 weeks for both the LED group and the placebo group.
The mean difference is calculated by taking the mean of differences of the entry scores minus the 3 week scores and the entry scores minus the 6 week scores.
D-KEFs color-word interferences, made up of color naming, word reading, and inhibition, is measured in seconds, a smaller number represents a better outcome.
Participants were given 90 seconds to complete color naming and word reading and 180 seconds to complete inhibition.
D-KEFs trail making test, made up of number sequencing, letter sequencing, and number-letter sequencing, is measured in seconds, a faster speed (lower number) represents a better outcome.
Participants were given 150 seconds to complete number and letter sequencing and 240 seconds to complete number-letter sequencing.
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From baseline to 3 weeks and from baseline to 6 weeks
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Mean Difference in Change in Delis-Kaplan Executive Function System (D-KEF) Verbal Fluency Performance at Weeks 3 and 6.
Time Frame: From baseline to 3 weeks and from baseline to 6 weeks
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This measure indicates the mean differences in Delis-Kaplan Executive Function System (D-KEF) tests between entry into the study and 3 weeks and entry into the study and 6 weeks for both the LED group and the placebo group.
The mean difference is calculated by taking the mean of differences of the entry scores minus the 3 week scores and the entry scores minus the 6 week scores.
D-KEFs Verbal Fluency Test, made up of letter fluency and category fluency, is measured by number of responses, a larger number represents a better outcome.
Participants were given 60 seconds to complete each fluency test.
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From baseline to 3 weeks and from baseline to 6 weeks
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Mean Difference in Change in Total Post Concussion Symptom Score (PCSS) at Weeks 3 and Weeks 6.
Time Frame: From baseline to 3 weeks and from baseline to 6 weeks
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This measure indicates the mean differences in total post concussion symptom score (PCSS) between entry into the study and 3 weeks and entry into the study and 6 weeks for both the LED group and the placebo group.
The mean difference is calculated by taking the mean of differences of the entry scores minus the 3 week scores and the entry scores minus the 6 week scores.
The PCSS is a sum of severity scores from 0-6 (0=none, 6=severe) for 22 individual symptoms, like headache, neck pain, or drowsiness.
The range for the PCSS is 0-132, a lower score represents a better outcome.
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From baseline to 3 weeks and from baseline to 6 weeks
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Mean Difference in Change in Total Cognitive Symptom Score at Weeks 3 and Weeks 6
Time Frame: From baseline to 3 weeks and from baseline to 6 weeks
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This measure indicates the mean difference in total cognitive symptom scores between entry into the study and 3 weeks and entry into the study and 6 weeks for both the LED group and the placebo group.
The mean difference is calculated by taking the mean of differences of the entry scores minus the 3 week scores and the entry scores minus the 6 weeks scores.
The total cognitive symptom scored is a sum of 7 symptom scores from the PCSS; feeling slowed down, feeling like "in a fog", "don't feel right", difficulty concentrating, difficulty remembering, fatigue or low energy, and confusion.
The severity of these symptoms are scored 0-6, 0=none, 6=severe.
The range for the total cognitive symptom score is 0-42, a lower score represents a better outcome.
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From baseline to 3 weeks and from baseline to 6 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William P Meehan, MD, Boston Children's Hospital
Publications and helpful links
General Publications
- Mochizuki-Oda N, Kataoka Y, Cui Y, Yamada H, Heya M, Awazu K. Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue. Neurosci Lett. 2002 May 3;323(3):207-10. doi: 10.1016/s0304-3940(02)00159-3.
- Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, Jordan BD. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005 Oct;57(4):719-26; discussion 719-26. doi: 10.1093/neurosurgery/57.4.719.
- McCrory P, Meeuwisse W, Johnston K, Dvorak J, Aubry M, Molloy M, Cantu R. Consensus statement on concussion in sport - The 3rd international conference on concussion in sport held in Zurich, November 2008. PM R. 2009 May;1(5):406-20. doi: 10.1016/j.pmrj.2009.03.010. No abstract available.
- Giza CC, Hovda DA. The Neurometabolic Cascade of Concussion. J Athl Train. 2001 Sep;36(3):228-235.
- Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med. 2008 Jan 31;358(5):453-63. doi: 10.1056/NEJMoa072972. Epub 2008 Jan 30.
- Meehan WP 3rd, Bachur RG. Sport-related concussion. Pediatrics. 2009 Jan;123(1):114-23. doi: 10.1542/peds.2008-0309.
- Omalu BI, DeKosky ST, Hamilton RL, Minster RL, Kamboh MI, Shakir AM, Wecht CH. Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery. 2006 Nov;59(5):1086-92; discussion 1092-3. doi: 10.1227/01.NEU.0000245601.69451.27.
- Stuss DT, Ely P, Hugenholtz H, Richard MT, LaRochelle S, Poirier CA, Bell I. Subtle neuropsychological deficits in patients with good recovery after closed head injury. Neurosurgery. 1985 Jul;17(1):41-7. doi: 10.1227/00006123-198507000-00007.
- Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin MR, Knight JA, Meehan WP 3rd, Baker EH. Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. J Neurotrauma. 2014 Jun 1;31(11):1008-17. doi: 10.1089/neu.2013.3244. Epub 2014 May 8.
- Delis DC, Kramer JH, Kaplan E, Holdnack J. Reliability and validity of the Delis-Kaplan Executive Function System: an update. J Int Neuropsychol Soc. 2004 Mar;10(2):301-3. doi: 10.1017/S1355617704102191. No abstract available.
- Cantu RC. Chronic traumatic encephalopathy in the National Football League. Neurosurgery. 2007 Aug;61(2):223-5. doi: 10.1227/01.NEU.0000255514.73967.90. No abstract available.
- Collins MW, Lovell MR, Iverson GL, Cantu RC, Maroon JC, Field M. Cumulative effects of concussion in high school athletes. Neurosurgery. 2002 Nov;51(5):1175-9; discussion 1180-1. doi: 10.1097/00006123-200211000-00011.
- Gronwall D, Wrightson P. Cumulative effect of concussion. Lancet. 1975 Nov 22;2(7943):995-7. doi: 10.1016/s0140-6736(75)90288-3.
- Guskiewicz KM, Mihalik JP, Shankar V, Marshall SW, Crowell DH, Oliaro SM, Ciocca MF, Hooker DN. Measurement of head impacts in collegiate football players: relationship between head impact biomechanics and acute clinical outcome after concussion. Neurosurgery. 2007 Dec;61(6):1244-52; discussion 1252-3. doi: 10.1227/01.neu.0000306103.68635.1a.
- Guskiewicz KM, McCrea M, Marshall SW, Cantu RC, Randolph C, Barr W, Onate JA, Kelly JP. Cumulative effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA. 2003 Nov 19;290(19):2549-55. doi: 10.1001/jama.290.19.2549.
- Jordan BD, Relkin NR, Ravdin LD, Jacobs AR, Bennett A, Gandy S. Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA. 1997 Jul 9;278(2):136-40.
- McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 2009 Jul;68(7):709-35. doi: 10.1097/NEN.0b013e3181a9d503.
- Beauchamp K, Mutlak H, Smith WR, Shohami E, Stahel PF. Pharmacology of traumatic brain injury: where is the "golden bullet"? Mol Med. 2008 Nov-Dec;14(11-12):731-40. doi: 10.2119/2008-00050.Beauchamp. Epub 2008 Aug 18.
- Mittenberg W, Burton DB. A survey of treatments for post-concussion syndrome. Brain Inj. 1994 Jul;8(5):429-37. doi: 10.3109/02699059409150994.
- Zafonte R, Friedewald WT, Lee SM, Levin B, Diaz-Arrastia R, Ansel B, Eisenberg H, Timmons SD, Temkin N, Novack T, Ricker J, Merchant R, Jallo J. The citicoline brain injury treatment (COBRIT) trial: design and methods. J Neurotrauma. 2009 Dec;26(12):2207-16. doi: 10.1089/neu.2009.1015.
- Meehan WP 3rd. Medical therapies for concussion. Clin Sports Med. 2011 Jan;30(1):115-24, ix. doi: 10.1016/j.csm.2010.08.003.
- Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain. 1974 Dec;97(4):633-54. doi: 10.1093/brain/97.1.633. No abstract available.
- Yamakami I, McIntosh TK. Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres. J Cereb Blood Flow Metab. 1989 Feb;9(1):117-24. doi: 10.1038/jcbfm.1989.16.
- Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res. 1991 Oct 4;561(1):106-19. doi: 10.1016/0006-8993(91)90755-k.
- Yuan XQ, Prough DS, Smith TL, Dewitt DS. The effects of traumatic brain injury on regional cerebral blood flow in rats. J Neurotrauma. 1988;5(4):289-301. doi: 10.1089/neu.1988.5.289.
- Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ. Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997 Dec;66(6):866-71. doi: 10.1111/j.1751-1097.1997.tb03239.x.
- Oron A, Oron U, Streeter J, de Taboada L, Alexandrovich A, Trembovler V, Shohami E. low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits. J Neurotrauma. 2007 Apr;24(4):651-6. doi: 10.1089/neu.2006.0198.
- Collins M, Lovell MR, Iverson GL, Ide T, Maroon J. Examining concussion rates and return to play in high school football players wearing newer helmet technology: a three-year prospective cohort study. Neurosurgery. 2006 Feb;58(2):275-86; discussion 275-86. doi: 10.1227/01.NEU.0000200441.92742.46.
- Field M, Collins MW, Lovell MR, Maroon J. Does age play a role in recovery from sports-related concussion? A comparison of high school and collegiate athletes. J Pediatr. 2003 May;142(5):546-53. doi: 10.1067/mpd.2003.190.
- Lovell MR, Collins MW, Iverson GL, Field M, Maroon JC, Cantu R, Podell K, Powell JW, Belza M, Fu FH. Recovery from mild concussion in high school athletes. J Neurosurg. 2003 Feb;98(2):296-301. doi: 10.3171/jns.2003.98.2.0296.
- Lovell MR, Collins MW, Iverson GL, Johnston KM, Bradley JP. Grade 1 or "ding" concussions in high school athletes. Am J Sports Med. 2004 Jan-Feb;32(1):47-54. doi: 10.1177/0363546503260723.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-P00002527
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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