Effect of Transcranial Near InfraRed Light On Cerebral Function in Young and Healthy Older Subjects: a fMRI Study (TIROC) (TIROC)

• ClinicalTrials.gov Identifier: NCT05845216
• Recruitment Status: Recruiting
• First Posted: May 6, 2023
• Last Update Posted: September 7, 2023
• Sponsor: University Hospital, Grenoble
• Collaborators: Commissariat A L'energie Atomique; Fonds de Dotation Clinatec
• Information provided by (Responsible Party): University Hospital, Grenoble

Tracking Information

• First Submitted Date: March 15, 2023
• First Posted Date: May 6, 2023
• Last Update Posted Date: September 7, 2023
• Actual Study Start Date: September 1, 2023
• Estimated Primary Completion Date: May 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2023)

Cerebral activations in response to a Finger Tapping motor task. [ Time Frame: 24 minutes ]

Cerebral activation measured by fMRI (BOLD signal change) in response to a finger tapping motor tap (contrasted against a resting baseline), before and after tPBM/Sham stimulation

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 2, 2023)

• Performances in the Finger Tapping motor task [ Time Frame: 24 minutes ]
  Performances in the Finger Tapping motor task (correct movement execution speed) before and after tPBM / Sham stimulation
• Functional connectivity (BOLD signal variations during the finger tapping task compared to rest state) [ Time Frame: 24 minutes ]
  Functional connectivity measured by fMRI (BOLD signal variation during the Finger tapping task compared to rest state) before and after tPBM / sham stimulation

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of Transcranial Near InfraRed Light On Cerebral Function in Young and Healthy Older Subjects: a fMRI Study (TIROC)
• Official Title: Effect of Transcranial Near InfraRed Light On Cerebral Function in Young and Healthy Older Subjects: a Functional Magnetic Resonance Imaging (fMRI) Study (TIROC)

Brief Summary

Numerous studies have shown that the extra-cranial application of near infrared light (λ=600-1000nm) (also called transcranial photobiomodulation or tPBM), has a positive impact on brain function in both humans and experimental animal models and a neuroprotective effect in animal models. Several of these studies have reported that tPBM could impart more beneficial effects in aged or diseased brains. The primary objective of this study is to use fMRI to compare the cerebral activations in response to a finger tapping motor task, before and after 24min of tPBM versus sham stimulation, in old and young healthy human subjects.

The hypothesis of the investigators is that tPBM improves brain function in participants who will be treated using the active device in comparison with those treated with the sham device and that this effect should will be more pronounced in the older subjects.

Detailed Description

Many studies have shown that the extra-cranial application of light in the red and near infrared range (λ=600-1000nm), also called transcranial PhotoBioModulation (tPBM), could have a neuroprotective effect and a positive impact on brain function in the mammalian brain.

At the cellular level, it is thought that the mechanism mainly relies on the activation of the cytochrome C oxidase and/or interfacial nanowater, two photoacceptors located within the mitochondria that absorb red and near infrared photons. The interaction between the photons and the photoacceptor results in a cascade of secondary events, activating the respiratory chain and increasing Adenosine TriPhosphate (ATP) synthesis, the main source of energy in the cell.

In humans, an increasing number of studies have reported an improvement of cognitive functions after one or several tPBM sessions in patients suffering Alzheimer's or Parkinson's disease, or in cases of stroke. Recently, some EEG and fMRI studies on healthy subjects, young and/or old, have also reported a modification of neuronal activation patterns at rest or during the performance of a cognitive task.

Regarding tPBM, this is a non-pharmacological and non-surgical treatment, for which no adverse effects have been reported. Further, the FDA has already approved the use of several PBM devices for therapeutic use in humans, for example, the treatment of pain, inflammation or dermal conditions.

Those preliminary results in humans are thus very encouraging. However, the precise mechanism of action remains to be better characterised, and further studies are required to better define its effects on the human brain and its indications for a therapeutic use. Moreover the extent tPBM influence on the brain of the elderly is still very unclear. In the present study, the investigators aim to evaluate brain function before and after a tPBM session, during the realisation of a motor task or at rest, while comparing a group of young and elderly subjects.

The working hypotheses of the investigators are as follows :

• tPBM will improve motor performances and brain function of all subjects, and to a greater extent that of the older subjects
• tPBM will change brain activity, reorganising large scale neuronal networks at rest.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

The Primary Purpose of this clinical trial is to test a prototype device for feasibility and not health outcomes. This study is conducted to confirm the design and operating specifications of a device before beginning a full clinical trial.

Masking: Single (Participant)
Primary Purpose: Other

• Condition: Healthy Volunteers

Intervention

• Device: ACTIVE Transcranial photobiomodulation (tPBM)
  fMRI records before and after ACTIVE Transcranial photobiomodulation (tPBM)
• Device: SHAM Transcranial photobiomodulation (tPBM)
  fMRI records before and after SHAM Transcranial photobiomodulation (tPBM)

Study Arms

• Experimental: ACTIVE tPBM
  one session of 24-min tPBM with the active device (tPBM helmet with 80 Light-Emitting Diodes (LEDs) emitting red and near-infrared light at 670 - 810nm)
  Intervention: Device: ACTIVE Transcranial photobiomodulation (tPBM)
• Sham Comparator: SHAM tPBM
  one session of 24-tPBM with a sham device visually identical to the active device
  Intervention: Device: SHAM Transcranial photobiomodulation (tPBM)

Publications *

• Dole M, Auboiroux V, Langar L, Mitrofanis J. A systematic review of the effects of transcranial photobiomodulation on brain activity in humans. Rev Neurosci. 2023 Mar 17;34(6):671-693. doi: 10.1515/revneuro-2023-0003. Print 2023 Aug 28.
• El Khoury H, Mitrofanis J, Henderson LA. Exploring the Effects of Near Infrared Light on Resting and Evoked Brain Activity in Humans Using Magnetic Resonance Imaging. Neuroscience. 2019 Dec 1;422:161-171. doi: 10.1016/j.neuroscience.2019.10.037. Epub 2019 Nov 1.
• Dmochowski GM, Shereen AD, Berisha D, Dmochowski JP. Near-Infrared Light Increases Functional Connectivity with a Non-thermal Mechanism. Cereb Cortex Commun. 2020 Mar 19;1(1):tgaa004. doi: 10.1093/texcom/tgaa004. eCollection 2020.
• Hamblin MR. Shining light on the head: Photobiomodulation for brain disorders. BBA Clin. 2016 Oct 1;6:113-124. doi: 10.1016/j.bbacli.2016.09.002. eCollection 2016 Dec.
• Nizamutdinov D, Qi X, Berman MH, Dougal G, Dayawansa S, Wu E, Yi SS, Stevens AB, Huang JH. Transcranial Near Infrared Light Stimulations Improve Cognition in Patients with Dementia. Aging Dis. 2021 Jul 1;12(4):954-963. doi: 10.14336/AD.2021.0229. eCollection 2021 Jul.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 2, 2023): 64
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 15, 2026
• Estimated Primary Completion Date: May 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Man or woman
• Aged 18 to 40 (young group), or 60 to 85 (elderly)
• Right-handed (Edinburgh score for hand laterality >70%)
• No taking psychoactive or anti-depressants medicine
• Normal or corrected vision
• Having expressed their consent to the research
• Affiliated to a social security scheme
• Registered in the national file of people lend themselves to biomedical research

Exclusion Criteria:

• Known cognitive disorder, neurologic trouble, neurodegenerative disease or psychiatric illness,
• Motor disorder able to impair the task management
• Contraindication for MRI (metallic implant, non-removable piercing, pace-maker, metallic prosthesis, claustrophobia , …)
• Montreal Cognitive Assessment (MoCA) score <26
• People referred to in Articles L1121-5 to L1121-8 of the Public Health Code(corresponds to all protected persons: pregnant, parturient or breastfeeding women, persons deprived of liberty by judicial or administrative decision, persons subject of psychiatric care, minors, and persons subject to a legal protection measure: guardianship, curators or safeguard of justice)
• Persons in period of exclusion from another clinical investigation
• Subjects participating in another clinic investigation,
• Subjects who would receive more than 4500 euros in compensation due to his participation in other biomedical research in the 12 months preceding this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Daniel ANGLADE, MD, PhD; 04 38 78 17 46; danglade@chu-grenoble.fr

Contact: Caroline SANDRE-BALLESTER, PhD; 0438782851; csandreballester@chu-grenoble.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05845216
• Other Study ID Numbers: 38RC22.0227
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Grenoble
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Grenoble
• Original Study Sponsor: Same as current

Collaborators

• Commissariat A L'energie Atomique
• Fonds de Dotation Clinatec

• Investigators: Not Provided
• PRS Account: University Hospital, Grenoble
• Verification Date: September 2023