Clinical trial NCT02817061: Effectiveness of Light for Enhancement of Cognition by Transcranial Repeated Application (ELECTRA)
Official title: Effectiveness of Light for Enhancement of Cognition by Transcranial Repeated Application (ELECTRA): a Placebo-Controlled Study of Efficacy, Tolerability and Acceptability in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Disease Type and/or Category Not Applicable
Keywords: no keywords for disease type and/or category
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-06-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Aim: Investigate whether transcranial photobiomodulation (tPBM) using near-infrared light exposure to the head, can improve frontal lobe executive function, working memory and overall mood in normal volunteer participants.

Hypothesis: The investigators predict that tPBM will increase cognitive functioning, as measured by Cambridge Cognition cognitive testing in study subjects.

Detailed description: Photobiomodulation (PBM), also called low-level light therapy (LLLT), uses optical power densities less than 100 mW/cm², and usually in the red (600-700 nm) or near infrared (NIR) 780-1000 nm wavelength range. Different light sources (coherent lasers or non-coherent LEDs) used for PBM have been shown to produce beneficial cellular effects and to be responsible for preservation and recovery of tissue function in controlled trials in a wide range of disorders typified by stress injury or degeneration. During PBM, absorption of red or near-infrared photons by cytochrome c oxidase in the mitochondrial respiratory chain causes an increase in cellular respiration that continues for much longer than the light is present when delivered at appropriate fluence and exposure durations.

Primary cellular effects include increases in mitochondrial activity and ATP levels, production of low levels of reactive oxygen species, induction of transcription factors (including the pro- survival NF-kB), and inhibition of apoptosis.

Over the past decade several studies have reported that a single, transcranial PBM treatment at 810 nm delivered to the head had significant, beneficial effect when used to treat acute ischemic stroke in several different animal models and also in human clinical trials. A similar approach was used to treat acute traumatic brain injury (TBI) in mice and in humans. Pathological examination of the mouse brains demonstrated up- regulation of brain-derived neurotrophic factor (BDNF) and stimulated neurogenesis in the hippocampus and increased synaptogenesis in the cortex.

A clinical trial is currently in progress at MGH to treat persons with acute moderate TBI. Several studies have shown improvement of cognitive function in persons with chronic TBI. Studies have also been conducted in animal models and in persons with Alzheimer's disease, Parkinson's disease, depression and anxiety.

Only a very limited number of studies have so far been carried out to test NIR photobiomodulation in normal experimental rodents and in normal human volunteers.

In this study, an LED array light source will be used that has been cleared by the FDA for other human uses.

Eligibility criteria: Inclusion Criteria:

* Age: 18-25 or 65-85
* Women of child-bearing potential, must use a double-barrier method for birth control (e.g. condoms with spermicide) if sexually active during the study and for 30 days post treatment of any kind.
* Subject Informed Consent obtained in writing in compliance with local regulations prior to enrollment into this study.
* The subject (and caregiver, if applicable) is willing to participate in this study for at least 12 weeks.

Exclusion Criteria:

* Inability to speak or read English (necessary for cognitive testing software use).
* Pregnancy or lactation
* History of stroke or traumatic brain injury
* Substance dependence or abuse in the past 6 months
* Diagnosis with major psychiatric disease (Psychotic disorder or psychotic episode, bipolar affective disorder)
* Diagnosed with a neurodevelopmental condition (autism or ADHD)
* A traumatic event that resulted in PTSD
* Any unstable medical illness (defined as any medical illness which has not been well-controlled with standard-of-care medications)
* A significant skin condition (i.e., hemangioma, scleroderma, rash, open wound) or medical implant (e.g. metal plate, implantable shunt or valve) on the head.
* Inability to understand or participate in the consent and performance of the study.
* Those with Parkinson's Disease, End Stage Renal Disease, and/or End Stage Liver Disease

Primary outcomes:
measure: ERT: Emotional Recognition Task
timeFrame: 16 weeks
measure: PAL: Paired Associates Learning
timeFrame: 16 weeks
measure: RTI: Reaction Time
timeFrame: 16 weeks
measure: RVP: Rapid Visual Information Processing
timeFrame: 16 weeks
measure: SST: Stop Signal Task
timeFrame: 16 weeks
measure: SWM: Spatial Working Memory
timeFrame: 16 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: MGH
name: R. Rox Anderson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Lapchak PA. Taking a light approach to treating acute ischemic stroke patients: transcranial near-infrared laser therapy translational science. Ann Med. 2010 Dec;42(8):576-86. doi: 10.3109/07853890.2010.532811. Epub 2010 Nov 1.
citation: Huang YY, Gupta A, Vecchio D, de Arce VJ, Huang SF, Xuan W, Hamblin MR. Transcranial low level laser (light) therapy for traumatic brain injury. J Biophotonics. 2012 Nov;5(11-12):827-37. doi: 10.1002/jbio.201200077. Epub 2012 Jul 17.
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citation: 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(10):108003. doi: 10.1117/1.JBO.19.10.108003.
citation: 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 Jun;8(6):502-11. doi: 10.1002/jbio.201400069. Epub 2014 Sep 8.
citation: Farfara D, Tuby H, Trudler D, Doron-Mandel E, Maltz L, Vassar RJ, Frenkel D, Oron U. Low-level laser therapy ameliorates disease progression in a mouse model of Alzheimer's disease. J Mol Neurosci. 2015 Feb;55(2):430-6. doi: 10.1007/s12031-014-0354-z. Epub 2014 Jul 4.
citation: Johnstone DM, Moro C, Stone J, Benabid AL, Mitrofanis J. Turning On Lights to Stop Neurodegeneration: The Potential of Near Infrared Light Therapy in Alzheimer's and Parkinson's Disease. Front Neurosci. 2016 Jan 11;9:500. doi: 10.3389/fnins.2015.00500. eCollection 2015.
citation: 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 Dec 8;5:46. doi: 10.1186/1744-9081-5-46.
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