Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression (TRIADE)

May 4, 2023 updated by: NYU Langone Health
This study will compare the effect of three transcranial photobiomodulation (t-PBM) doses (high, middle, and low irradiance) to sham t-PBM on PFC CBF as assessed with fMRI (BOLD) in this multi-center, phase I, double-blinded, dose-ranging, controlled, crossover study of 30 subjects with MDD. All eligible participants will undergo four sessions of t-PBM during fMRI so that they experience irradiances of 50, 300 and 700 mW/cm2 as well as sham. The order of dose administration will be randomized and t-PBM will be administered with the LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purpose of this research study is to determine if application of near infrared energy to the forehead can change blood flow in the brains of people with depression. Near infrared energy is like light but is not visible to the human eye. This research study will compare near infrared exposure with a placebo or sham procedure. The sham procedure will look and feel just like the near infrared procedure but won't include near infrared exposure.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Charlestown, Massachusetts, United States, 02129
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10016
        • New York University
      • Orangeburg, New York, United States, 10962
        • Nathan Kline Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must be able to give written informed consent and follow study procedures

  • Participants must have major depressive disorder; all the following conditions need to be met to ensure presence of significant depression symptoms:

    1. Meeting diagnostic criteria for Major Depressive Disorder (MDD) in the past two weeks, at the DSM-5 Mini-International Neuropsychiatric Interview (MINI)
    2. Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening
    3. Depression symptoms are the primary target of treatment or treatment-seeking.
  • Women of child-bearing potential must agree to use adequate contraception
  • Participants taking medications or psychotherapy approved for the treatment of major depressive disorder will need to be stable for at least 8 weeks prior to screen

Exclusion Criteria:

  • Unwilling or unable to comply with study requirements
  • Participants who are judged to be at serious and imminent suicidal (C-SSRS≥4) or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority
  • History of any or psychotic or bipolar disorder
  • Alcohol or substance use disorder, post-traumatic stress disorder, obsessive-compulsive disorder and eating disorders within the preceding 12 months
  • History of dementia, traumatic brain injury (TBI), or neurological disorders affecting the brain, including any history of stroke or seizure disorders requiring treatment in the last 5 years (even if controlled with medications)
  • Cognitive impairment significant as determined by the Montreal Cognitive Assessment (MOCA) <22
  • History of antisocial personality disorder, or any clinically significant personality trait that would, in the investigator's judgment, preclude safe study participation or impair ability to remain adherent with the treatment protocol.
  • History of significant treatment non-adherence or situations where the subjects are unlikely to adhere to treatment, in the opinion of the investigator
  • Pregnant (as confirmed by pregnancy test at screen) or nursing.
  • Currently undergoing device-based treatment for depression or taking medications for depression other than SSRIs or SNRIs.
  • Treatment resistance with failure to respond to more than two adequate treatments with FDA-approved antidepressant medications during current episode of major depressive disorder.
  • History of ECT in the last 12 months; lifetime history of VNS; lifetime treatment resistance to any FDA-approved device-based treatment for major depressive disorder; device-based interventions for depression will need to be discontinued at least 8 weeks prior to screen.
  • Serious, unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, hematologic disease; defined as any medical illness which is not well-controlled with standard-of-care medications
  • Clinically significant abnormal findings of laboratory parameters including urine toxicology screen for drugs of abuse or at physical examination
  • Clinical or laboratory evidence of uncontrolled hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before screening.
  • Past intolerance or hypersensivity to t-PBM.
  • Significant skin conditions on the subject's scalp that are found in the area of the procedure sites.
  • Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
  • Any type of implants in the head, whose functioning might be affected by t-PBM.
  • Failure to meet standard MRI safety requirements as determined by the MRI Safety Checklist.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Patients with MDD
Participants will undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose (50 mW/cm2; 300 mW/cm2; 770 mW/cm2), as well as a sham dose (0 mW/cm2), once over the 4 treatment visits.
Device: Transcranial Photobiomodulator
Delivers laser-generated Near-Infrared Radiation (NIR) to forehead at 3 doses of irradiance - High (770 mW/cm2), Middle (300 mW/cm2), and Low (50 mW/cm2).
Other Names:
  • LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0)
Device: Sham
Transcranial Photobiomodulator delivers sham irradiance dose of 0 mW/cm2.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During High-Irradiance t-PBM
Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans.

Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7
Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Middle-Irradiance t-PBM
Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans.

Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7
Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Low-Irradiance t-PBM
Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans.

Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7
Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Sham Treatment
Time Frame: 20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans.

Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.
20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Columbia Suicide Severity Rating Scale (C-SSRS) Suicide Ideation Score
Time Frame: Baseline, Follow-up (Week 8)
C-SSRS systematically tracks suicidal ideation and behavior. The total score range is 0 (no ideation is present) to 5 (active suicidal ideation with specific plan and intent). The higher the score, the greater one's suicidal ideation. Any score greater than 0 is important and may indicate the need for mental health intervention.
Baseline, Follow-up (Week 8)
Change in Brain Temperature During High-Irradiance t-PBM
Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Change in Brain Temperature During Middle-Irradiance t-PBM
Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Change in Brain Temperature During Low-Irradiance t-PBM
Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Change in Brain Temperature During Sham Treatment
Time Frame: Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Changes computed using data recorded with magnetic resonance (MR) thermometry scans taken immediately before and after the 20-minute transcranial photobiomodulation (t-PBM) treatment administration.
Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7
Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Prior to First Treatment
Time Frame: Baseline
55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects
Baseline
Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following High-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total
55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects
Immediately Post-Intervention, up to Week 7 in total
Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Middle-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total
55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects
Immediately Post-Intervention, up to Week 7 in total
Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Low-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total
55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects
Immediately Post-Intervention, up to Week 7 in total
Systematic Assessment for Treatment Emergent Events (SAFTEE) Score Following Sham Treatment
Time Frame: Immediately Post-Intervention, up to Week 7 in total
55-item self-assessment measuring severity levels of side effects. Participants rank each item on a 4-point Likert scale ranging from 0-3, where: 0 = None; 1 = Mild; 2 = Moderate; and 3 = Severe. The total score is the sum of responses. Scores range from 0 to 165; higher scores indicate greater severity of side effects
Immediately Post-Intervention, up to Week 7 in total
t-PBM Self-Report Questionnaire (TSRQ) Score Following High-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total

3-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales.

The total score is the sum of responses. Total score ranges from 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
Immediately Post-Intervention, up to Week 7 in total
t-PBM Self-Report Questionnaire (TSRQ) Score Following Middle-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total

3-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales.

The total score is the sum of responses. Total score ranges from 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
Immediately Post-Intervention, up to Week 7 in total
t-PBM Self-Report Questionnaire (TSRQ) Score Following Low-Irradiance t-PBM
Time Frame: Immediately Post-Intervention, up to Week 7 in total

3-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales.

The total score is the sum of responses. Total score ranges from 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
Immediately Post-Intervention, up to Week 7 in total
t-PBM Self-Report Questionnaire (TSRQ) Score Following Sham Treatment
Time Frame: Immediately Post-Intervention, up to Week 7 in total

3-item self-report assessment of potential inconveniences and discomforts from the transcranial photobiomodulation (t-PBM). Participants rank each item on various Likert scales.

The total score is the sum of responses. Total score ranges from 3-18; higher scores indicate greater perceived inconveniences and discomforts associated with t-PBM use.
Immediately Post-Intervention, up to Week 7 in total

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NYU Langone Health

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dan Iosifescu, MD, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 24, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 17, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 5, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20-00217
  • 1R61MH122647-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

IPD Sharing Time Frame

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

IPD Sharing Access Criteria

The investigator who proposed to use the data and upon reasonable request. Requests should be directed to Dr. Kate Collins, PhD (email: Kate.Collins@nki.rfmh.org). To gain access, data requestors will need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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