Mild Cognitive Impairment (MCI)LTMCNCT07651787
Using Light Therapy for Mild Cognitive Impairment
A study testing Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation in people with Mild Cognitive Impairment (MCI) and Amyloid Pathology, run by University of Oklahoma at 1 site in United States.
Trial summary
The goal of this clinical trial is to test whether transcranial photobiomodulation (tPBM), a non-invasive brain stimulation technique using near-infrared light, can improve brain blood flow regulation (neurovascular coupling) and cognitive function in people with mild cognitive impairment (MCI). Read more about this study
- Who is it for?
- Ages 55 to 95 years
- Conditions the study is for
- Mild Cognitive Impairment (MCI), Amyloid Pathology
- What is being tested?
- Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: 55-95 years of age
- Clinical Dementia Rating (CDR) equal to 0.5 and/or Montreal Cognitive Assessment (MoCA) <26 and ≥19
- Adequate hearing and visual acuity to participate in the examinations
- English speaker
- Presence of cerebrovascular pathology confirmed by structural brain imaging method
Who cannot join
- Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
- Cerebrovascular accident other than TIA within 60 days prior to Visit 0
- Diagnosis of amyloid angiopathy
- Major psychiatric disease, including major depression not controlled on medications, alcohol or drug abuse
- Neurodegenerative diseases, e.g: Parkinson's, any kind of dementia
- Patients currently using commercial brain stimulation / neuromodulation device as part of a research study
Show all 10Show fewer
- Patients currently take dietary supplements with an expected cerebrovascular benefit such as NAD- or NR-supplementum, L-citrullin, urolithin
- Unstable medical condition, including uncontrolled diabetes, chronic heart issues, heart failure, chronic obstructive pulmonary disease, hypertension uncontrolled by medication (>160/100 mmHg)
- Any other medical condition or medication which, in the opinion of investigator, would render the patient too unstable to complete the study protocol
- Severe sensory deficits interfering with the testing
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Oklahoma Health Campus
Oklahoma City, Oklahoma, 73104
Leslie Guthery, MS, 405-271-4113, leslie-guthery@ou.edu
OUHSC Director Office of H.R.P.P., +1 (405) 271 2045
About this study
Official title: Neurovascular and Mitochondrial Mechanisms of Transcranial Photobiomodulation in Vascular Mild Cognitive Impairment
The goal of this clinical trial is to test whether transcranial photobiomodulation (tPBM), a non-invasive brain stimulation technique using near-infrared light, can improve brain blood flow regulation (neurovascular coupling) and cognitive function in people with mild cognitive impairment (MCI). The main questions it aims to answer are:
- Does tPBM enhance cognitive function and cerebral hemodynamic responses during memory and finger tapping tasks?
- Does tPBM reduce oxidative stress, inflammation, and mitigate brain cell damage?
- Is cognitive improvement linked to amyloid status, greater cerebral hemodynamic response, and lower levels of brain inflammation and oxidative stress? Researchers will compare an active tPBM treatment arm to a sham treatment arm to see if tPBM leads to measurable improvements in brain activity and cognitive function compared to no active stimulation.
Read more
Participants will:
- Receive a 20-minute-long active tPBM or sham stimulation session once per day, 6 times per week, for 12 weeks.
- Complete questionnaires and an iPad-based cognitive testing protocol.
- Complete memory and motor tasks while their brain activity is measured using non-invasive techniques: simultaneous functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). Dynamic analysis of the vessels in the eye will also be performed based on eligibility. Transcranial Doppler (TCD) flowmetry is optionally performed.
- Provide blood samples to test for biomarkers of inflammation, oxidative stress, and brain cell damage.
Read the detailed description
Cognitive impairment represents a major source of disability, with vascular pathologies playing a critical role in the development and progression of cognitive dysfunction. In particular, vascular cognitive impairment (VCI) is a common and clinically relevant contributor to cognitive decline in individuals with MCI. Despite substantial advances in understanding the underlying mechanisms of VCI, effective therapeutic interventions remain limited. Neurons require continuous energy supply, which is provided by the physiological process, called Neurovascular coupling (NVC), a dynamical redistribution of local cerebral blood flow to meet neuronal activity. NVC is essential to maintain optimal brain function. Evidence from our preclinical and clinical work, in line with findings from other research groups, increasingly implicates NVC dysregulation as a key mechanism underlying cognitive deficits in MCI, underscoring the need for targeted interventions aimed at restoring neurovascular function.
Transcranial photobiomodulation has emerged as a promising, non-invasive approach with the potential to support both neuronal and vascular health. By delivering near-infrared light to cortical tissue, tPBM has the potential to enhance mitochondrial activity, reduce oxidative stress, and improve cerebral hemodynamics. A growing body of literature demonstrates the beneficial effects of red and near-infrared light across a range of neurological, cardiovascular, and cerebrovascular conditions. However, the neurophysiological mechanisms underlying these effects remain insufficiently characterized in humans, and the therapeutic potential of tPBM has yet to be fully explored in clinical populations such as individuals with MCI. Optical imaging modalities, including near-infrared spectroscopy (NIRS), provide an opportunity to assess tPBM-induced changes in cerebral oxygenation and hemodynamics in real-world settings, thereby improving the feasibility and translational relevance of studies investigating cerebrovascular mechanisms in MCI. Further practical advantages of tPBM lie in its documented safe application, affordability, and simplicity of use; these factors support the utilization of tPBM in potential home-based interventions.
Recent studies have demonstrated a close association between cognitive performance and NVC responses both in healthy individuals and in patients with MCI. Neuronal activity-induced vasodilation is largely mediated by nitric oxide, whose bioavailability is enhanced by tPBM through its dissociation from cytochrome c oxidase. In addition, tPBM has been shown to exert anti-inflammatory effects within the brain, a mechanism that is particularly relevant given evidence of elevated neuroinflammatory processes in MCI. Despite these promising findings, clinical evidence directly examining the effects of tPBM on NVC remains limited. Existing studies have primarily focused on cognitive outcomes, with relatively little emphasis on underlying neurophysiological or hemodynamic changes and minimal integration of these measures. Addressing this gap, the present study aims to employ advanced multimodal neuroimaging techniques to investigate tPBM-induced modulation of NVC in individuals with MCI and to examine its relationship with cognitive performance.
Preclinical and early clinical studies indicate that tPBM enhances microvascular perfusion and tissue oxygenation while concurrently reducing neuroinflammation and oxidative stress. These complementary effects highlight tPBM as a multifaceted intervention capable of targeting both neural and vascular dysfunction. To date, tPBM has demonstrated a favorable safety profile across diverse populations, with transient and mild headache being the most commonly reported adverse effect. Its non-pharmacological nature and compatibility with existing therapeutic strategies further support its potential role in cognitive rehabilitation.
The significance of this project lies in its potential to advance a novel, non-invasive intervention for cognitive impairment in patients with MCI, as well as in its capacity to elucidate the neurovascular mechanisms through which tPBM exerts its effects. By clarifying how tPBM modulates NVC and related cognitive outcomes, this research will provide a foundation for future mechanism-driven and combination therapeutic approaches aimed at mitigating cognitive decline associated with MCI.
- Conditions
- Mild Cognitive Impairment (MCI), Amyloid Pathology
- Being tested
- Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation, Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulation
- Keywords
- Cognition, Neurovascular Coupling Mechanism and Cognitive Function, Neurovascular Control, Brain Aging, Brain Activity, Mild Congitive Impairment (MCI), Amyloid, Transcranial photobiomodulation, Near-infrared spectroscopy, Cerebral hemodynamics, Near-infrared light therapy, NIH Toolbox Cognition Battery, Electroencephalography, Amyloid-positive mild cognitive impairment, Amyloid-negative mild cognitive impairment, Extracellular vesicles, Neuroinflammation, Proinflammatory cytokines, Home-based neuromodulation, Non-invasive brain stimulation
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulationDevice
Also called tPBM, near-infrared light therapy
The active Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used to transmit pulsed near-infrared (NIR) energy through the cranium. The device emits NIR photons at an 810-nm wavelength, generating ~250 mW/cm² of pulsed NIR power modulated at 10 and 40 Hz frequencies (Alpha and Gamma modes). The six NIR light sources are positioned along the midline over the frontal, parietal, and occipital cortices, bilaterally over the temporal cortices, and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home.
Active photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session.
Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulationDevice
Also called tPBM, near-infrared light therapy
Sham Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used. These devices are identical in appearance to the active devices; however, they do not emit near-infrared (NIR) light at an 810-nm wavelength. The six light sources are positioned along the midline over the frontal, parietal, and occipital cortices; bilaterally over the temporal cortices; and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home.
Sham photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session.
| Study group | Role | What they receive |
|---|---|---|
| Active near-infrared light therapy | Active comparator | Participants in this arm will receive 20-minute active transcranial photobiomodulation sessions six times a week for 12 weeks during their participation in the study. The intervention will be administered using an active Vielight Neuro RX-Duo, a research version of a commercially available light therapy device categorized as a wellness product with non-significant risk. During these sessions, biologically effective near-infrared light will be administered. Receives: Device: Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation |
| Sham near-infrared light therapy | Sham comparator | Participants in this arm will receive 20-minute sham transcranial photobiomodulation sessions six times a week for 12 weeks during their participation in the study. The intervention will be administered using a sham Vielight Neuro RX-Duo, a research version of a commercially available light therapy device categorized as a wellness product with non-significant risk. During these sessions, biologically effective near-infrared light will not be administered. Receives: Device: Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cortical neurovascular coupling
Functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. EEG records electrical potential changes in the brain cortex. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment, normalized to change in EEG. The change in regression coefficient reflecting change in neurovascular coupling responses is a dimensionless measure.
Measured: From baseline visit to the follow-up visit after completing a 12 week intervention protocol
Secondary outcomes (1)
Change in fluid cognition composite score
NIH Toolbox will be used to assess fluid cognitive performance by calculating a composite score based on subscores from select tests targeting relevant domains, including attention, working memory, and executive function, as described in other pre-specified outcomes. Units of measure - score (from 0 to 200, the bigger the number, the better). Reported as a %change from baseline, before and after intervention.
Measured: From baseline visit to the follow-up visit after completing a 12 week intervention protocol.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2026
- Study start1 Oct 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (63)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive Impairment (MCI)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, parallel-group, double-blind, sham-controlled trial. Adult (55-85 years of age) participants with MCI will be randomized in a 1:1 ratio to receive either active transcranial photobiomodulation or sham stimulation. Participants in both groups will complete one 20 minutes long session per day , 6 times per week for 12 weeks. Cognitive and physiological outcomes will be measured at baseline and post-intervention follow-up.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oklahoma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Mukli, MD, PhD, Principal investigator, Department of Neurosurgery, University of Oklahoma Health Campus, Oklahoma, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07651787
- Sponsor's protocol ID
- 19237
- Other IDs
- 128958
- Acronym
- LTMC
- Status last verified
- Jun 2026
- First submitted
- 27 May 2026
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: To ensure compliance, investigators will establish data management and sharing practices that align with NIH standards, including the timely submission of datasets to public repositories such as SenNet consortium, Figshare, SPARC portal and OpenNeuro. Invetigators will also publish findings in peer-reviewed journals registered in PubMed centrals to prevent unintentional duplication of research. All data generated in this project and the detailed description of the methods will be published in journals accessible through NIH databases.
Publications
Rashidi-Ranjbar N, Churchill NW, Graham SJ, Schneider R, Rajji TK, Andreazza AC, Lim L, Coull J, Munoz DG, Fornazzari LR, Schweizer TA, Fischer CE. A pilot study evaluating the feasibility, safety, and efficacy of transcranial photobiomodulation (tPBM) for the treatment of mild cognitive impairment (MCI): preliminary findings. Alzheimers Dement. 2024;20(Suppl 8). Epub 20250109. doi: 10.1002/alz.095049; PMCID: PMC11713276.
Apaijai N, Sriwichaiin S, Phrommintikul A, Jaiwongkam T, Kerdphoo S, Chansirikarnjana S, Thongmung N, Mahantassanapong U, Vathesatogkit P, Kitiyakara C, Sritara P, Chattipakorn N, Chattipakorn SC. Cognitive impairment is associated with mitochondrial dysfunction in peripheral blood mononuclear cells of elderly population. Sci Rep. 2020 Dec 8;10(1):21400. doi: 10.1038/s41598-020-78551-4.
PubMed 33293556Rodriguez-Fernandez L, Zorzo C, Arias JL. Photobiomodulation in the aging brain: a systematic review from animal models to humans. Geroscience. 2024 Dec;46(6):6583-6623. doi: 10.1007/s11357-024-01231-y. Epub 2024 Jun 11.
PubMed 38861125Lee TL, Ding Z, Chan AS. Can transcranial photobiomodulation improve cognitive function? A systematic review of human studies. Ageing Res Rev. 2023 Jan;83:101786. doi: 10.1016/j.arr.2022.101786. Epub 2022 Nov 9.
PubMed 36371017Cassano P, Petrie SR, Hamblin MR, Henderson TA, Iosifescu DV. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics. 2016 Jul;3(3):031404. doi: 10.1117/1.NPh.3.3.031404. Epub 2016 Mar 4.
PubMed 26989758Spera V, Sitnikova T, Ward MJ, Farzam P, Hughes J, Gazecki S, Bui E, Maiello M, De Taboada L, Hamblin MR, Franceschini MA, Cassano P. Pilot Study on Dose-Dependent Effects of Transcranial Photobiomodulation on Brain Electrical Oscillations: A Potential Therapeutic Target in Alzheimer's Disease. J Alzheimers Dis. 2021;83(4):1481-1498. doi: 10.3233/JAD-210058.
PubMed 34092636Salehpour F, Mahmoudi J, Kamari F, Sadigh-Eteghad S, Rasta SH, Hamblin MR. Brain Photobiomodulation Therapy: a Narrative Review. Mol Neurobiol. 2018 Aug;55(8):6601-6636. doi: 10.1007/s12035-017-0852-4. Epub 2018 Jan 11.
PubMed 29327206Csiszar A, Ungvari A, Patai R, Gulej R, Yabluchanskiy A, Benyo Z, Kovacs I, Sotonyi P, Kirkpartrick AC, Prodan CI, Liotta EM, Zhang XA, Toth P, Tarantini S, Sorond FA, Ungvari Z. Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages. Geroscience. 2024 Oct;46(5):5103-5132. doi: 10.1007/s11357-024-01139-7. Epub 2024 Apr 19.
PubMed 38639833Du J, Ma M, Zhao Q, Fang L, Chang J, Wang Y, Fei R, Song X. Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia. Neuroscience. 2013 Feb 12;231:345-52. doi: 10.1016/j.neuroscience.2012.11.062. Epub 2012 Dec 8.
PubMed 23232258Cai Y, Mok VCT, Markus HS. Vascular dementia: World Stroke Organization fact sheet 2026. Int J Stroke. 2026 Feb;21(2):152-163. doi: 10.1177/17474930251404243. Epub 2026 Jan 1.
PubMed 41479247Sachdev PS, Lipnicki DM, Kochan NA, Crawford JD, Thalamuthu A, Andrews G, Brayne C, Matthews FE, Stephan BC, Lipton RB, Katz MJ, Ritchie K, Carriere I, Ancelin ML, Lam LC, Wong CH, Fung AW, Guaita A, Vaccaro R, Davin A, Ganguli M, Dodge H, Hughes T, Anstey KJ, Cherbuin N, Butterworth P, Ng TP, Gao Q, Reppermund S, Brodaty H, Schupf N, Manly J, Stern Y, Lobo A, Lopez-Anton R, Santabarbara J; Cohort Studies of Memory in an International Consortium (COSMIC). The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration. PLoS One. 2015 Nov 5;10(11):e0142388. doi: 10.1371/journal.pone.0142388. eCollection 2015.
PubMed 26539987Goldman JG, Holden SK, Litvan I, McKeith I, Stebbins GT, Taylor JP. Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment. Mov Disord. 2018 Apr;33(4):503-510. doi: 10.1002/mds.27323. Epub 2018 Feb 28.
PubMed 29488270Ponjoan A, Garre-Olmo J, Blanch J, Fages E, Alves-Cabratosa L, Marti-Lluch R, Comas-Cufi M, Parramon D, Garcia-Gil M, Ramos R. Epidemiology of dementia: prevalence and incidence estimates using validated electronic health records from primary care. Clin Epidemiol. 2019 Mar 4;11:217-228. doi: 10.2147/CLEP.S186590. eCollection 2019.
PubMed 308811382020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020 Mar 10. doi: 10.1002/alz.12068. Online ahead of print.
PubMed 32157811Roig-Carles D, Willms E, Fontijn RD, Martinez-Pacheco S, Mager I, de Vries HE, Hirst M, Sharrack B, Male DK, Hawkes CA, Romero IA. Endothelial-Derived Extracellular Vesicles Induce Cerebrovascular Dysfunction in Inflammation. Pharmaceutics. 2021 Sep 21;13(9):1525. doi: 10.3390/pharmaceutics13091525.
PubMed 34575601
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurovascular and Mitochondrial Mechanisms of Transcranial Photobiomodulation in Vascular Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT07651787
- Acronym / sponsor ID
- LTMC / 19237
- Conditions
- Mild Cognitive Impairment (MCI), Amyloid Pathology
- Keywords
- Cognition, Neurovascular Coupling Mechanism and Cognitive Function, Neurovascular Control, Brain Aging, Brain Activity, Mild Congitive Impairment (MCI), Amyloid, Transcranial photobiomodulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of OklahomaUniversity, hospital or other
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 16 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to test whether transcranial photobiomodulation (tPBM), a non-invasive brain stimulation technique using near-infrared light, can improve brain blood flow regulation (neurovascular coupling) and cognitive function in people with mild cognitive impairment (MCI). The main questions it aims to answer are:
- Does tPBM enhance cognitive function and cerebral hemodynamic responses during memory and finger tapping tasks?
- Does tPBM reduce oxidative stress, inflammation, and mitigate brain cell damage?
- Is cognitive improvement linked to amyloid status, greater cerebral hemodynamic response, and lower levels of brain inflammation and oxidative stress? Researchers will compare an active tPBM treatment arm to a sham treatment arm to see if tPBM leads to measurable improvements in brain activity and cognitive function compared to no active stimulation.
Participants will:
- Receive a 20-minute-long active tPBM or sham stimulation session once per day, 6 times per week, for 12 weeks.
- Complete questionnaires and an iPad-based cognitive testing protocol.
- Complete memory and motor tasks while their brain activity is measured using non-invasive techniques: simultaneous functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). Dynamic analysis of the vessels in the eye will also be performed based on eligibility. Transcranial Doppler (TCD) flowmetry is optionally performed.
- Provide blood samples to test for biomarkers of inflammation, oxidative stress, and brain cell damage.
Detailed description
Cognitive impairment represents a major source of disability, with vascular pathologies playing a critical role in the development and progression of cognitive dysfunction. In particular, vascular cognitive impairment (VCI) is a common and clinically relevant contributor to cognitive decline in individuals with MCI. Despite substantial advances in understanding the underlying mechanisms of VCI, effective therapeutic interventions remain limited. Neurons require continuous energy supply, which is provided by the physiological process, called Neurovascular coupling (NVC), a dynamical redistribution of local cerebral blood flow to meet neuronal activity. NVC is essential to maintain optimal brain function. Evidence from our preclinical and clinical work, in line with findings from other research groups, increasingly implicates NVC dysregulation as a key mechanism underlying cognitive deficits in MCI, underscoring the need for targeted interventions aimed at restoring neurovascular function.
Transcranial photobiomodulation has emerged as a promising, non-invasive approach with the potential to support both neuronal and vascular health. By delivering near-infrared light to cortical tissue, tPBM has the potential to enhance mitochondrial activity, reduce oxidative stress, and improve cerebral hemodynamics. A growing body of literature demonstrates the beneficial effects of red and near-infrared light across a range of neurological, cardiovascular, and cerebrovascular conditions. However, the neurophysiological mechanisms underlying these effects remain insufficiently characterized in humans, and the therapeutic potential of tPBM has yet to be fully explored in clinical populations such as individuals with MCI. Optical imaging modalities, including near-infrared spectroscopy (NIRS), provide an opportunity to assess tPBM-induced changes in cerebral oxygenation and hemodynamics in real-world settings, thereby improving the feasibility and translational relevance of studies investigating cerebrovascular mechanisms in MCI. Further practical advantages of tPBM lie in its documented safe application, affordability, and simplicity of use; these factors support the utilization of tPBM in potential home-based interventions.
Recent studies have demonstrated a close association between cognitive performance and NVC responses both in healthy individuals and in patients with MCI. Neuronal activity-induced vasodilation is largely mediated by nitric oxide, whose bioavailability is enhanced by tPBM through its dissociation from cytochrome c oxidase. In addition, tPBM has been shown to exert anti-inflammatory effects within the brain, a mechanism that is particularly relevant given evidence of elevated neuroinflammatory processes in MCI. Despite these promising findings, clinical evidence directly examining the effects of tPBM on NVC remains limited. Existing studies have primarily focused on cognitive outcomes, with relatively little emphasis on underlying neurophysiological or hemodynamic changes and minimal integration of these measures. Addressing this gap, the present study aims to employ advanced multimodal neuroimaging techniques to investigate tPBM-induced modulation of NVC in individuals with MCI and to examine its relationship with cognitive performance.
Preclinical and early clinical studies indicate that tPBM enhances microvascular perfusion and tissue oxygenation while concurrently reducing neuroinflammation and oxidative stress. These complementary effects highlight tPBM as a multifaceted intervention capable of targeting both neural and vascular dysfunction. To date, tPBM has demonstrated a favorable safety profile across diverse populations, with transient and mild headache being the most commonly reported adverse effect. Its non-pharmacological nature and compatibility with existing therapeutic strategies further support its potential role in cognitive rehabilitation.
The significance of this project lies in its potential to advance a novel, non-invasive intervention for cognitive impairment in patients with MCI, as well as in its capacity to elucidate the neurovascular mechanisms through which tPBM exerts its effects. By clarifying how tPBM modulates NVC and related cognitive outcomes, this research will provide a foundation for future mechanism-driven and combination therapeutic approaches aimed at mitigating cognitive decline associated with MCI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomized, parallel-group, double-blind, sham-controlled trial. Adult (55-85 years of age) participants with MCI will be randomized in a 1:1 ratio to receive either active transcranial photobiomodulation or sham stimulation. Participants in both groups will complete one 20 minutes long session per day , 6 times per week for 12 weeks. Cognitive and physiological outcomes will be measured at baseline and post-intervention follow-up.
| Arm | Type | Receives |
|---|---|---|
| Active near-infrared light therapy | Active comparator | Device: Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulationParticipants in this arm will receive 20-minute active transcranial photobiomodulation sessions six times a week for 12 weeks during their participation in the study. The intervention will be administered using an active Vielight Neuro RX-Duo, a research version of a commercially available light therapy device categorized as a wellness product with non-significant risk. During these sessions, biologically effective near-infrared light will be administered. |
| Sham near-infrared light therapy | Sham comparator | Device: Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulationParticipants in this arm will receive 20-minute sham transcranial photobiomodulation sessions six times a week for 12 weeks during their participation in the study. The intervention will be administered using a sham Vielight Neuro RX-Duo, a research version of a commercially available light therapy device categorized as a wellness product with non-significant risk. During these sessions, biologically effective near-infrared light will not be administered. |
Who may qualify
- Ages
- 55 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age: 55-95 years of age
- Clinical Dementia Rating (CDR) equal to 0.5 and/or Montreal Cognitive Assessment (MoCA) <26 and ≥19
- Adequate hearing and visual acuity to participate in the examinations
- English speaker
- Presence of cerebrovascular pathology confirmed by structural brain imaging method
Key exclusion criteria (10 listed)
- Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer
- Cerebrovascular accident other than TIA within 60 days prior to Visit 0
- Diagnosis of amyloid angiopathy
- Major psychiatric disease, including major depression not controlled on medications, alcohol or drug abuse
- Neurodegenerative diseases, e.g: Parkinson's, any kind of dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulationAlso: tPBM, near-infrared light therapyThe active Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used to transmit pulsed near-infrared (NIR) energy through the cranium. The device emits NIR photons at an 810-nm wavelength, generating ~250 mW/cm² of pulsed NIR power modulated at 10 and 40 Hz frequencies (Alpha and Gamma modes). The six NIR light sources are positioned along the midline over the frontal, parietal, and occipital cortices, bilaterally over the temporal cortices, and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home. Active photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session. | Device | Active near-infrared light therapy |
| Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulationAlso: tPBM, near-infrared light therapySham Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used. These devices are identical in appearance to the active devices; however, they do not emit near-infrared (NIR) light at an 810-nm wavelength. The six light sources are positioned along the midline over the frontal, parietal, and occipital cortices; bilaterally over the temporal cortices; and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home. Sham photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session. | Device | Sham near-infrared light therapy |
Primary outcome
Change in cortical neurovascular coupling
Time frame: From baseline visit to the follow-up visit after completing a 12 week intervention protocol
Functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. EEG records electrical potential changes in the brain cortex. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment, normalized to change in EEG. The change in regression coefficient reflecting change in neurovascular coupling responses is a dimensionless measure.
1 secondary outcome
Change in fluid cognition composite score
Time frame: From baseline visit to the follow-up visit after completing a 12 week intervention protocol.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
- BackgroundRashidi-Ranjbar N, Churchill NW, Graham SJ, Schneider R, Rajji TK, Andreazza AC, Lim L, Coull J, Munoz DG, Fornazzari LR, Schweizer TA, Fischer CE. A pilot study evaluating the feasibility, safety, and efficacy of transcranial photobiomodulation (tPBM) for the treatment of mild cognitive impairment (MCI): preliminary findings. Alzheimers Dement. 2024;20(Suppl 8). Epub 20250109. doi: 10.1002/alz.095049; PMCID: PMC11713276.
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- Background: PubMed 38861125Rodriguez-Fernandez L, Zorzo C, Arias JL. Photobiomodulation in the aging brain: a systematic review from animal models to humans. Geroscience. 2024 Dec;46(6):6583-6623. doi: 10.1007/s11357-024-01231-y. Epub 2024 Jun 11.
- Background: PubMed 36371017Lee TL, Ding Z, Chan AS. Can transcranial photobiomodulation improve cognitive function? A systematic review of human studies. Ageing Res Rev. 2023 Jan;83:101786. doi: 10.1016/j.arr.2022.101786. Epub 2022 Nov 9.
- Background: PubMed 26989758Cassano P, Petrie SR, Hamblin MR, Henderson TA, Iosifescu DV. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics. 2016 Jul;3(3):031404. doi: 10.1117/1.NPh.3.3.031404. Epub 2016 Mar 4.
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- Background: PubMed 38639833Csiszar A, Ungvari A, Patai R, Gulej R, Yabluchanskiy A, Benyo Z, Kovacs I, Sotonyi P, Kirkpartrick AC, Prodan CI, Liotta EM, Zhang XA, Toth P, Tarantini S, Sorond FA, Ungvari Z. Atherosclerotic burden and cerebral small vessel disease: exploring the link through microvascular aging and cerebral microhemorrhages. Geroscience. 2024 Oct;46(5):5103-5132. doi: 10.1007/s11357-024-01139-7. Epub 2024 Apr 19.
- Background: PubMed 23232258Du J, Ma M, Zhao Q, Fang L, Chang J, Wang Y, Fei R, Song X. Mitochondrial bioenergetic deficits in the hippocampi of rats with chronic ischemia-induced vascular dementia. Neuroscience. 2013 Feb 12;231:345-52. doi: 10.1016/j.neuroscience.2012.11.062. Epub 2012 Dec 8.
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- Background: PubMed 26539987Sachdev PS, Lipnicki DM, Kochan NA, Crawford JD, Thalamuthu A, Andrews G, Brayne C, Matthews FE, Stephan BC, Lipton RB, Katz MJ, Ritchie K, Carriere I, Ancelin ML, Lam LC, Wong CH, Fung AW, Guaita A, Vaccaro R, Davin A, Ganguli M, Dodge H, Hughes T, Anstey KJ, Cherbuin N, Butterworth P, Ng TP, Gao Q, Reppermund S, Brodaty H, Schupf N, Manly J, Stern Y, Lobo A, Lopez-Anton R, Santabarbara J; Cohort Studies of Memory in an International Consortium (COSMIC). The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration. PLoS One. 2015 Nov 5;10(11):e0142388. doi: 10.1371/journal.pone.0142388. eCollection 2015.
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- Transcranial photobiomodulation research using VielightLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. To ensure compliance, investigators will establish data management and sharing practices that align with NIH standards, including the timely submission of datasets to public repositories such as SenNet consortium, Figshare, SPARC portal and OpenNeuro. Invetigators will also publish findings in peer-reviewed journals registered in PubMed centrals to prevent unintentional duplication of research. All data generated in this project and the detailed description of the methods will be published in journals accessible through NIH databases.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Mukli, MD, PhD principal investigator
Department of Neurosurgery, University of Oklahoma Health Campus, Oklahoma, USA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation in people with Mild Cognitive Impairment (MCI) and Amyloid Pathology, run by University of Oklahoma at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Peter Mukli (+1 (405) 271-8001 ext. 37745, peter-mukli@ou.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cortical neurovascular coupling (time frame: From baseline visit to the follow-up visit after completing a 12 week intervention protocol). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07651787, which also lists 63 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.