PBM Effects on Health and Well-being in Humans

Effects and Underlying Mechanisms of Photobiomodulation (PBM) on Health and Well-Being

The goal of this clinical study is to assess the effects of different photobiomodulation (PBM) conditions in men and women between 25 and 65 years old with daytime sleepiness/drowsiness and /or mild mood complaints but be otherwise healthy. The main question it aims to answer are:

1. Does PBM significantly affect health and well-being?
2. Are PBM effects wavelength dependent?
3. Are PBM effects pulse dependent?
4. Are the eyes needed to assert an PBM effect or is exposure only to the skin sufficient?
5. What are the cellular, metabolic pathways underlying the systemic effects of PBM.

Participants will have to:

1. Exposed themselves 5 times per week during 2 weeks to the PBM stimuli between 9:30 and 12:30.
2. A week before the baseline measurement, participants will have to start wearing a Fitbit Versa 3, and will have to continuously wear until the end of the study.
3. In the afternoon of the baseline day as well as in the afternoons after 5 and 10 PBM sessions (week 1 and week 2, respectively), participants will have to go to the lab for blood withdraw.
4. In the evening of the baseline day as well as in the evenings after 5 and 10 PBM sessions (week 1 and week 2, respectively), participants will have to collect saliva samples as well as to complete questionnaires.

It will be a double-blind placebo-controlled field study with a between subject comparison.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep Deprivation; Circadian Rhythm Disorders
• Intervention / Treatment: Device: PBM

Detailed Description

Five conditions (groups) will be tested:

Dose (J.cm-2) Wavelength (nm) Pulse (Hz,ms) Duty factor Area Cond 1 6.5 850 15, 8 12% Skin + eyes Cond 2 6.5 940 15, 8 12% Skin + eyes Cond 3 6.5 850 100, 1 12% Skin + eyes Cond 4 0 850 15, 8 12% Skin + eyes Cond 5 6.5 850 15, 8 12% Skin

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marina Gimenez, PhD; Phone Number: +31502111946; Email: marina.gimenez@chronoatwork.com
• Study Contact Backup: Name: Michelle Luxwolda, MSc; Phone Number: 31502111946; Email: michelle.luxwolda@chronoatwork.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Healthy, no chronic disease

• Age between 25 - 65 years.
• Suffer from daytime sleepiness/drowsiness and or a mild mood disturbance (ESS >5 or BDI equal to or higher than 13 but lower than 20, PSQI > 5)
• Participants will have to have a desk type of work and/or have 3 hours per day between 9:30 am and 12:30 at their office/home in which they could sit in front of the lamp.

Exclusion Criteria:

Depressive mood (BDI -II > 20)

• Pregnancy
• Menopause symptoms
• Drug use during the last three months known to interfere with sleep, alertness, the biological clock and/or light sensitivity (i.e. regular usage of sleep medication or stimulating substances)
• Use of immune suppressants. High levels of caffeine intake during a day (5 or more cups, according to https://www.voedingscentrum.nl/encyclopedie/cafeine.aspx#blok7, there are no negative effects expected from 4 caffeine products in normal adults)
• High alcohol intake (more than 4 for men and more than 3 for women, drinks per day) for more than 5 days in the past month, including binge drinking and heavy drinking according to https://www.niaaa.nih.gov/publications/brochures-and- fact-sheets/alcohol-facts-and-statistics.
• Participant is not able to refrain from using recreational drugs during the 4 weeks of the study.
• Shift work schedule in the 3 months prior to participation and/or planned during the 2 weeks of the study
• Environmental factors in everyday life that may disturb sleep and cannot be prohibited (e.g. young children, noisy environment)
• Travel over 2 or more time zones in the month prior to participation
• Travel to sunny holiday locations/wintersports 1 month before participation
• Personal plans that prevent them for using the intervention during 2 consecutive weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: placebo; No PBM will be emitted from the device; dose: 0 J.cm-2
Experimental: PBM High standard; A PBM high standard dose of 6.5 J.cm-2 with a wavelength of 850 nm, a pulse of 15 Hz and 8 ms and duty factor of 12%	Device: PBM; In this study, the health benefits of the addition of NIR to the light spectrum of a desk lamp already available in the market will be investigate; Ikea Ypeperlig, to which a module with high power Lumileds NIR-Leds will be attached with beam angle of 90 degrees. They will be attached in such a way that, when the lamp is installed in the right place, a 1sr beam that covers the users face, neck and hands and lower arms on the desk with the required intensity of 5mW/cm2 of NIR at the skin surface. The device will be equipped with 3 sensors: A distance sensor connected to the driver of the NIR-leds, such that when the user leans forward or backward, the intensity of the NIR is automatically adjusted such that the intensity on the skin remains 5mW/cm2 (see figure below).; a presence sensor; ambient vertical lux sensor by which amount of light that enters the users' eye will be measured since it is known that these have an effect sleep, mood and performance.
Experimental: PBM High wavelength; A PBM high dose of 6.5 J.cm-2 with a wavelength of 940 nm, a pulse of 15 Hz and 8 ms and duty factor of 12%	Device: PBM; In this study, the health benefits of the addition of NIR to the light spectrum of a desk lamp already available in the market will be investigate; Ikea Ypeperlig, to which a module with high power Lumileds NIR-Leds will be attached with beam angle of 90 degrees. They will be attached in such a way that, when the lamp is installed in the right place, a 1sr beam that covers the users face, neck and hands and lower arms on the desk with the required intensity of 5mW/cm2 of NIR at the skin surface. The device will be equipped with 3 sensors: A distance sensor connected to the driver of the NIR-leds, such that when the user leans forward or backward, the intensity of the NIR is automatically adjusted such that the intensity on the skin remains 5mW/cm2 (see figure below).; a presence sensor; ambient vertical lux sensor by which amount of light that enters the users' eye will be measured since it is known that these have an effect sleep, mood and performance.
Experimental: PBM High pulse; A PBM high dose of 6.5 J.cm-2 with a wavelength of 850 nm, a pulse of 100 Hz and 1.2 ms and duty factor of 12%	Device: PBM; In this study, the health benefits of the addition of NIR to the light spectrum of a desk lamp already available in the market will be investigate; Ikea Ypeperlig, to which a module with high power Lumileds NIR-Leds will be attached with beam angle of 90 degrees. They will be attached in such a way that, when the lamp is installed in the right place, a 1sr beam that covers the users face, neck and hands and lower arms on the desk with the required intensity of 5mW/cm2 of NIR at the skin surface. The device will be equipped with 3 sensors: A distance sensor connected to the driver of the NIR-leds, such that when the user leans forward or backward, the intensity of the NIR is automatically adjusted such that the intensity on the skin remains 5mW/cm2 (see figure below).; a presence sensor; ambient vertical lux sensor by which amount of light that enters the users' eye will be measured since it is known that these have an effect sleep, mood and performance.
Experimental: PBM High skin only; A PBM high standard dose of 6.5 J.cm-2 with a wavelength of 850 nm, a pulse of 15 Hz and 8 ms and duty factor of 12%, but in this case the participants will wear filtering googles which will not allow PBM from entering the eyes	Device: PBM; In this study, the health benefits of the addition of NIR to the light spectrum of a desk lamp already available in the market will be investigate; Ikea Ypeperlig, to which a module with high power Lumileds NIR-Leds will be attached with beam angle of 90 degrees. They will be attached in such a way that, when the lamp is installed in the right place, a 1sr beam that covers the users face, neck and hands and lower arms on the desk with the required intensity of 5mW/cm2 of NIR at the skin surface. The device will be equipped with 3 sensors: A distance sensor connected to the driver of the NIR-leds, such that when the user leans forward or backward, the intensity of the NIR is automatically adjusted such that the intensity on the skin remains 5mW/cm2 (see figure below).; a presence sensor; ambient vertical lux sensor by which amount of light that enters the users' eye will be measured since it is known that these have an effect sleep, mood and performance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in subjective mood after 5 and after 10 PBM sessions	Mood VAS scale, 0-10, higher score means better	Baseline, after 2 weeks, after 4 weeks
Change from baseline in subjective drowsiness after 5 and after 10 PBM sessions	Epworth Sleepiness Scale, 0-24, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in depressions scale after 5 and after 10 PBM sessions	Beck Depression Inventory Second Edition, 0-63, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in general activation after 5 and after 10 PBM sessions	Activation-Deactivation check list, 5-20, higher score means better	Baseline, after 2 weeks, after 4 weeks
Change from baseline in deactivation after 5 and after 10 PBM sessions	Activation-Deactivation check list, 11-14, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in high activation after 5 and after 10 PBM sessions	Activation-Deactivation check list, 5-20, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in general deactivation after 5 and after 10 PBM sessions	Activation-Deactivation check list, 5-20, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in subjective sleep quality scores after 5 and after 10 PBM sessions	Pittsburgh Sleep quality scale, 0-21, higher score means worse	Baseline, after 2 weeks, after 4 weeks
Change from baseline in resting heart rate after 5 and after 10 PBM sessions	Fitbit Versa 3	Through study completion
Change from baseline in objective sleep quality scores after 5 and after 10 PBM sessions	Fitbit Versa 3	Through study completion
Change from baseline in IFN- gamma concentrations after 5 and after 10 PBM sessions	Blood	Baseline, after 2 weeks, after 4 weeks
Change from baseline in TNF-alpha concentrations after 5 and after 10 PBM sessions	Blood	Baseline, after 2 weeks, after 4 weeks
Change from baseline in TGF-beta1concentrations after 5 and after 10 PBM sessions	Blood	Baseline, after 2 weeks, after 4 weeks
Change from baseline in il-1 concentrations after 5 and after 10 PBM sessions	Blood	Baseline, after 2 weeks, after 4 weeks
Change from baseline in il-6 concentrations after 5 and after 10 PBM sessions	Blood	Baseline, after 2 weeks, after 4 weeks
Shift from baseline in dim light melatonin onset after 5 and after 10 PBM sessions	Saliva	Baseline, after 2 weeks, after 4 weeks
Change from baseline in cortisol levels at bedtime after 5 and after 10 PBM sessions	Saliva	Baseline, after 2 weeks, after 4 weeks
Change from baseline in targeted metabolomics concentration after 5 and after 10 PBM sessions	Blood	Baseline, after 4 weeks

Collaborators and Investigators

• Sponsor: Seaborough Life Science B.V.
• Collaborators: University of Groningen; Chrono@Work B.V.
• Investigators: Principal Investigator: Marijke Gordijn, PhD, Chrono@Work

Publications and helpful links

General Publications

• Fulop AM, Dhimmer S, Deluca JR, Johanson DD, Lenz RV, Patel KB, Douris PC, Enwemeka CS. A meta-analysis of the efficacy of laser phototherapy on pain relief. Clin J Pain. 2010 Oct;26(8):729-36. doi: 10.1097/AJP.0b013e3181f09713.
• Heiskanen V, Pfiffner M, Partonen T. Sunlight and health: shifting the focus from vitamin D3 to photobiomodulation by red and near-infrared light. Ageing Res Rev. 2020 Aug;61:101089. doi: 10.1016/j.arr.2020.101089. Epub 2020 May 25.
• Liebert A, Bicknell B, Markman W, Kiat H. A Potential Role for Photobiomodulation Therapy in Disease Treatment and Prevention in the Era of COVID-19. Aging Dis. 2020 Dec 1;11(6):1352-1362. doi: 10.14336/AD.2020.0901. eCollection 2020 Dec.
• Miranda-Silva W, Gomes-Silva W, Zadik Y, Yarom N, Al-Azri AR, Hong CHL, Ariyawardana A, Saunders DP, Correa ME, Arany PR, Bowen J, Cheng KKF, Tissing WJE, Bossi P, Elad S; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society for Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients. Support Care Cancer. 2021 Jul;29(7):3539-3562. doi: 10.1007/s00520-020-05803-4. Epub 2020 Nov 6.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): May 31, 2023

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Sleep Deprivation; Chronobiology Disorders
• Other Study ID Numbers: PBM2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No