Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Study protocol

Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial

Authors: João Gustavo Rocha Peixoto dos Santos, Ana Luiza Costa Zaninotto, Renato Amaro Zângaro, Ana Maria Costa Carneiro, Iuri Santana Neville, Almir Ferreira de Andrade, Manoel Jacobsen Teixeira, Wellingson Silva Paiva

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800–900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients.

Methods/design

This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm2, 10 J/cm2) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation.

Discussion

This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials.

Trial registration

ClinicalTrials.gov, NCT03281759. Registered on 13 September 2017.
Appendix
Available only for authorised users
Literature
1.
Langlois JA, Rutland-Brown W, Thomas KE. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil. 2006;21(6):544–8.CrossRefPubMed
2.
3.
Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil. 2010;25(2):72–80.CrossRefPubMed
4.
Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P, Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization in the United States. J Head Trauma Rehabil. 2008;23(2):123–31.CrossRefPubMed
5.
Parizel PM, Ozsarlak O, Van Goethem JW, et al. Imaging findings in diffuse axonal injury after closed head trauma. Eur Radiol. 1998;8:960–5.CrossRefPubMed
6.
Meythaler JM, Peduzzi JD, Eleftheriou E, Novack TA. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehabil. 2001;82(10):1461–71.CrossRefPubMed
7.
Adams JH, Mitchell DE, Graham DI, Doyle D. Diffuse brain damage of immediate impact type: its relationship to “primary brain-stem damage” in head injury. Brain. 1977;100:489–502.CrossRefPubMed
8.
McLellan, DR. The structural bases of coma and recovery: insights from brain injury in humans and experimental animals. In: Sandel ME, Ellis DW, editors. The coma-emerging patient. Philadelphia: Hanley & Belfus; 1990. p. 389–407.
9.
Donnell AJ, Kim MS, Silva MA, Vanderploeg RD. Incidence of postconcussion symptoms in psychiatric diagnostic groups, mild traumatic brain injury, and comorbid conditions. Clin Neuropsychol. 2012;26(7):1092–101.CrossRefPubMed
10.
Naeser MA, Hamblin MR. Traumatic brain injury: a major medical problem that could be treated using transcranial, red/near-infrared LED photobiomodulation. Photomed Laser Surg. 2015;33(9):443–6.CrossRefPubMedPubMedCentral
11.
Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R, Lee H, Meeker M, Zimmerman RD, Manley GT, McCandliss BD. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol. 2008;29:967–73.CrossRefPubMed
12.
Bazarian JJ, Mcclung J, Shah MN, Cheng YT, Flesher W, Kraus J. Mild traumatic brain injury in the United States, 1998–2000. Brain Inj. 2005;19:113–21.CrossRef
13.
Cantu RC. Concussion classification: ongoing controversy. In: Slobounov S, Sebastianelli W, editors. Foundations of sports-related brain injuries. New York: Springer; 2006. p. 87–110.CrossRef
14.
Wang H, Duan G, Zhang J. Clinical features and CT diagnostic criteria for diffuse axonal brain injury. Zhonghua Wai Ke Za Zhi. 1996;34(4):229–31.PubMed
15.
Lindel R, Gentry LR. Imaging of closed head injury. Radiology. 1994;191:1–17.CrossRef
16.
17.
Bazarian JJ, Zhong J, Blyth B, Zhu T, Kavcic V, Peterson D. Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. J Neurotrauma. 2007;24:1447–59.CrossRefPubMed
18.
Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996;111(3):209–19.CrossRefPubMed
19.
Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Photomed Laser Surg. 2011;29:351–8.CrossRefPubMedPubMedCentral
20.
21.
22.
Wan S, Parrish JA, Anderson RR, Madden M. Transmittance of nonionizing radiation in human tissues. Photochem Photobiol. 1981;34:679–81.CrossRefPubMed
23.
Pitzschke A, Lovisa B, Seydoux O, Zellweger M, Pfleiderer M, Tardy Y, Wagnières G. Red and NIR light dosimetry in the human deep brain. Phys Med Biol. 2015;60:2921–37.CrossRefPubMed
24.
Whelan HT, Smits RL Jr, Buchman EV, Whelan NT, Turner SG, Margolis DA, Cevenini V, Stinson H, Ignatius R, Martin T, Cwiklinski J, Philippi AF, Graf WR, Hodgson B, Gould L, Kane M, Chen G, Caviness J. Effects of NASA light-emitting diode irradiation on wound healing. J Clin Laser Med Surg. 2001;19:305–14.CrossRefPubMed
25.
Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L, Rubin O, Wolf T, Ben HS. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Lasers Surg Med. 2001;28:204–11.CrossRefPubMed
26.
Naeser M, Ho M, Martin PE, Treglia EM, Krengel M, Hamblin MR, Baker EH. Improved language after scalp application of red/near-infrared light-emitting diodes: pilot study supporting a new, noninvasive treatment for chronic aphasia. Procedia Soc Behav Sci. 2012;61:138–9.CrossRef
27.
Xuan W, Vatansever F, Huang L, Hamblin MR. Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice. J Biomed Opt. 2014;19:108003.CrossRefPubMedPubMedCentral
28.
Desmet KD, Paz DA, Corry JJ, Eells JT, Wong-Riley MT, Henry MM, Buchmann EV, Connelly MP, Dovi JV, Liang HL, Henshel DS, Yeager RL, Millsap DS, Lim J, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT. Clinical and experimental applications of NIR-LED photobiomodulation. Photomed Laser Surg. 2006;24(2):121–8.CrossRefPubMed
29.
Karu T. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B. 1999;49:1–17.CrossRefPubMed
30.
Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M, Whelan HT. Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase. J Biol Chem. 2005;280:4761–71.CrossRefPubMed
31.
Homsi S, Piaggio T, Croci N, Noble F, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neurotrauma. 2010;27(5):911–21.CrossRefPubMed
32.
Sompol P, Xu Y, Ittarat W, Daosukho C, St Clair D. NF-kappa B-associated MnSOD induction protects against beta-amyloid-induced neuronal apoptosis. J Mol Neurosci. 2006;29:279–88.CrossRef
33.
Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct. 2009;5:46.CrossRefPubMedPubMedCentral
34.
Ambrogini P, Lattanzi D, Ciuffoli S, Betti M, Fanelli M, Cuppini R. Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF. Brain Res. 2013;1534:1–12.CrossRefPubMed
35.
Richardson RM, Sun D, Bullock MR. Neurogenesis after traumatic brain injury. Neurosurg Clin N Am. 2007;18(1):169–81.CrossRefPubMed
36.
Naeser MA, Martins PI, Ho MD, Krengel MH1, Bogdanova Y, Knight JA, Yee MK1, Zafonte R, Frazier J, Hamblin MR, Koo BB. Transcranial, red/near-infrared light-emitting diode therapy to improve cognition in chronic traumatic brain injury. Photomed Laser Surg. 2016;34(12):610–26.CrossRefPubMed
37.
Xuan W, Agrawal T, Huang L, Gupta GK, Hamblin MR. Low-level laser therapy for traumatic brain injury in mice increases brain derived neurotrophic factor (BDNF) and synaptogenesis. J Biophotonics. 2015;8:502–11.CrossRefPubMed
38.
Wu Q, Huang Y-Y, Dhital S, et al. Low level laser therapy for traumatic brain injury. SPIE Proc. 2010;7552:755206–8.CrossRef
39.
Haeussinger FB, Heinzel S, Hahn T, Schecklmann M, Ehlis AC, Fallgatter AJ. Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging. PLoS One. 2011;6
40.
Strangman GE, Zhang Q, Li Z. Scalp and skull influence on near infrared photon propagation in the Colin27 brain template. NeuroImage. 2014;85:136–49.CrossRefPubMed
41.
Okada E, Delpy DT. Near-infrared light propagation in an adult head model. II. Effect of superficial tissue thickness on the sensitivity of the near-infrared spectroscopy signal. Appl Opt. 2003;42:2915–22.CrossRefPubMed
42.
Jagdeo JR, Adams LE, Brody NI, Siegel DM. Transcranial red and near infrared light transmission in a cadaveric model. PLoS One. 2012;7
43.
The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Age. J Neurotrauma. 2000;17:573–81.CrossRef
44.
Gennarelli TA. Cerebral concussion and diffuse brain injuries. In: Cooper PR, editor. Head injury. 3rd ed. Baltimore: Williams & Wilkins; 1993. p. 137–58.
45.
Smith DH, Meaney DF, Shull WH. Diffuse axonal injury in head trauma. J Head Trauma Rehabil. 2003;18(4):307–16.CrossRefPubMed
46.
Tomei G, Sganzerla E, Spagnoli D, Guerra P, Lucarini C, Gaini SM, Villani R. Posttraumatic diffuse cerebral lesions. Relationship between clinical course, CT findings and ICP. J Neurosurg Sci. 1991;35(2):61–75.PubMed
47.
Gennarelli TA, Wodzin E. Abbreviated Injury Scale 2005—update 2008. Des Plaines: AAAM; 2008.
48.
Ohle R, McIsaac SM, Woo MY, Perry JJ. Sonography of the optic nerve sheath diameter for detection of raised intracranial pressure compared to computed tomography. J Ultrasound Med. 2015;34:1285–94.CrossRefPubMed
49.
Hendricks HT, Heeren AH, Vos PE. Dysautonomia after severe traumatic brain injury. Eur J Neurol. 2010;17(9):1172–7.CrossRefPubMed
50.
Bullock MR, Chesnut RM, Clifton GL, The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Guidelines for the management of severe traumatic brain injury. Brain Trauma Foundation. J Neurotrauma. 2000:17:449-554.
51.
52.
Salgado ASI, Zangaro RA, Parreira RB, Kerppers II. The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women. Lasers Med Sci. 2015;30:339.CrossRefPubMed
53.
54.
55.
Pettigrew LE, Wilson JT, Teasdele GM. Assessing disability after head injury: improved use of the Glasgow Outcome Scale. J Neurosurg. 1998;89(6):939–43.CrossRefPubMed
56.
57.
Jennett B, Snoek J, Bond MR, Brooks N. Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry. 1981;44:285–93.CrossRefPubMedPubMedCentral
58.
Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989;15(1):49–59.CrossRefPubMed
59.
Marshall LF, Marshall SB, Klauber MR, Clark MB, Eisenberg HM, Jane JA, Luerssen TG, Marmarou A, Foulkes MA. A new classification of head injury based on computerized tomography. J Neurosurg. 1991;75:S14–20.
60.
Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery. 2005;57(6):1173–82.CrossRefPubMed
61.
Bagiella E, Novack TA, Ansel B, et al. Measuring outcome in traumatic brain injury treatment trials: recommendations from the traumatic brain injury clinical trials network. J Head Trauma Rehabil. 2010;25(5):375–82.CrossRefPubMedPubMedCentral
62.
Edwards P, Arango M, Balica L, Cottingham R, El-Sayed H, Farrell B, Fernandes J, Gogichaisvili T, Golden N, Hartzenberg B, Husain M, Ulloa MI, Jerbi Z, Khamis H, Komolafe E, Laloe V, Lomas G, Ludwig S, Mazairac G, Munoz Sanchez Mde L, Nasi L, Olldashi F, Plunkett P, Roberts I, Sandercock P, Shakur H, Soler C, Stocker R, Svoboda P, Trenkler S, CRASH trial collaborators, et al. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months. Lancet. 2005;365:1957–9.CrossRefPubMed
63.
de CA VR, Paiva WS, de Oliveira DV, Teixeira MJ, de Andrade AF, de Sousa RMC. Diffuse axonal injury: epidemiology, outcome and associated risk factors. Front Neurol. 2016;7:178.
64.
65.
U.S. Department of Health and Human Services. Health Insurance Portability and Accountability Act of 1996 (HIPAA) privacy, security and breach notification rules, vol. 104: USA public law; 1996. p. 191.
66.
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;24(4):651–6.CrossRefPubMed
67.
Michalikova S, Ennaceur A, van Rensburg R, Chazot PL. Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light. Neurobiol Learn Mem. 2008;89(4):480–8.CrossRefPubMed
68.
Bogdanova Y, Martin P, Ho MD, Krengel MH, Ho VT, Yee MK, Knight JA, Hamblin M, Naeser MA. LED therapy improves sleep and cognition in chronic moderate TBI: pilot case studies. Arch Phys Med Rehabil. 2014;95:e77.CrossRef
69.
Naeser MA, 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;31:1008–17.CrossRefPubMedPubMedCentral
70.
Henderson TA, Morries LD. SPECT perfusion imaging demonstrates improvement of traumatic brain injury with transcranial near-infrared laser phototherapy. Adv Mind Body Med. 2015;29:27–33.PubMed
71.
King JT Jr, Carlier PM, Marion DW. Early Glasgow Outcome Scale scores predict long-term functional outcome in patients with severe traumatic brain injury. J Neurotrauma. 2005;22(9):947–54.CrossRefPubMed
Metadata
Title
Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial
Authors
João Gustavo Rocha Peixoto dos Santos
Ana Luiza Costa Zaninotto
Renato Amaro Zângaro
Ana Maria Costa Carneiro
Iuri Santana Neville
Almir Ferreira de Andrade
Manoel Jacobsen Teixeira
Wellingson Silva Paiva
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2632-5

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Effects of traditional Chinese herbal medicine in patients with diabetic kidney disease: study protocol for a randomized controlled trial

Study protocol

The impact of an exercise training intervention on cortisol levels and post-traumatic stress disorder in juveniles from an Ugandan refugee settlement: study protocol for a randomized control trial

Study protocol

Comparison of outcome measures and complication rates following three different approaches for primary total hip arthroplasty: a pragmatic randomised controlled trial

Research

WASH Benefits Bangladesh trial: management structure for achieving high coverage in an efficacy trial

Research

Successful recruitment to trials: findings from the SCIMITAR+ Trial

Study protocol

Effectiveness and safety of bifidobacteria and berberine in people with hyperglycemia: study protocol for a randomized controlled trial