Near-Infrared Laser Stimulation for Various Neurological Conditions

Study Overview
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Brief Summary
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The study will evaluate the safety and feasibility of near infrared therapy as an intervention for patients with refractory depression, anxiety, neurodegenerative disease, and traumatic brain injury.

Detailed Description
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The present study is being undertaken as an open-label study to evaluate the safety and feasibility of near infrared therapy as an intervention for patients with refractory depression, anxiety, cognitive impairment due to a neurodegenerative disease (e.g., Alzheimer's), and traumatic brain injury. Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures. The present study can be easily implemented because instruments have been in routine clinical deployment providing for a high degree of availability and reliability. Quality assurance is tightly controlled. The study population is sufficiently broad and the conditions of interest are sufficiently prevalent so that recruitment of subjects is not a limiting factor.

Official Title
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Use of Near Infrared Laser Stimulation for Treatment of Depression, Anxiety, Neurodegenerative Conditions, and Traumatic Brain Injury/Chronic Traumatic Encephalopathy

Conditions
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Refractory Depression, Anxiety Disorders, Neurodegenerative Diseases, Traumatic Brain Injury, Chronic Traumatic Encephalopathy

Intervention / Treatment
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* Device: Near Infrared Laser Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (depression): Diagnosis of Major Depressive Disorder Score greater than 13 on the Beck Depression Inventory Failure to remit with 3 antidepressants At least 18 years of age Inclusion Criteria (anxiety): Diagnosis of Generalized or Acute Anxiety Disorder Score greater than 22 on the Beck Anxiety Inventory Failure to remit with 3 anxiolytics At least 18 years of age Inclusion Criteria (neurodegenerative dementia): Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia (CDR stage 2) Lumbar puncture for Abeta 42 and Tau proteins evincing clinical correlation of neurodegenerative disease pathology Advanced MRI of the brain including volume measurement of the hippocampus, blood-oxygen level dependent imaging, and arterial spin labeling perfusion scans. On entry, patients will have CDR stage of at least 0.5 and at least one abnormal imaging biomarker. Inclusion criteria (TBI/CTE): Diagnosis of Traumatic Brain Injury or Chronic Traumatic Encephalopathy At least 18 years of age Exclusion Criteria: Macular degeneration Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer) Advanced kidney, pulmonary, cardiac or liver failure Advanced terminal illness Any active cancer or chemotherapy Bone marrow disorder Myeloproliferative disorder Sickle cell disease Primary pulmonary hypertension Immunocompromising conditions and/or immunosuppressive therapies Any other neoplastic illness or illness characterized by neovascularity Subjects unable to give informed consent Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep Recent surgery or dental work within 3 months of the scheduled procedure. Pregnancy, women who may become pregnant or are breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The present study is being undertaken as an open-label study to evaluate the safety and feasibility of near infrared therapy as an intervention for patients with refractory depression, anxiety, cognitive impairment due to a neurodegenerative disease (e.g., Alzheimer's), and traumatic brain injury.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Near Infrared Laser Therapy<br>On the days of each near-infrared therapy session, patients will undergo 10 minutes of transcranial infrared laser stimulation. The laser dose for all conditions will be a 3.4 W continuous laser wave, at a 1064 wavelength, with irradiance (power density) at 250 milli-Watts/cm2. All groups will have treatment once a week (10 minutes per session) for 5-6 weeks. For Alzheimer's, the site targeted will be the right prefrontal cortex. Parkinson's patients will have laser delivered to the brain stem, bilateral temporal lobes. TBI/CTE patients will have the laser stimulation site dependent on location of injury. Patients with depression/anxiety will have laser stimulation applied to the prefrontal area of the head. | Device: Near Infrared Laser Stimulation<br>* 10 minutes of transcranial near infrared laser stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [Depression (MDD)] Beck Depression Inventory (BDI-II) | The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from 0 (this item does not apply) to 3 (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant. | 6 weeks | 
| [Anxiety] Beck Anxiety Inventory (BAI) | The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful. | 6 weeks | 
| [Dementia] Quick Dementia Rating Scale (QDRS) | The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). | 6 weeks | 
| [Concussion/Traumatic Brain Injury (TBI)] Brief Pain Inventory (BPI) | Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 6 weeks | 
| [All] Global Rating of Change (GRC) | The GRC consists of a single likert-scale ranging from -5 (very much worse) to 0 (neutral/no change) to 5 (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| [MDD & TBI] Patient Depression Questionnaire (PDQ-9) | The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from 0 (not at all), 1 (several days/week), 2 (more than half of the days), and 3 (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful. | 6 weeks | 
| [MDD & TBI] Patient Depression Questionnaire (PDQ-9) | The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from 0 (not at all), 1 (several days/week), 2 (more than half of the days), and 3 (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful. | 4 weeks post last day of treatment | 
| [MDD] Hamilton Depression Rating Scale (HAM-D) | The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of 0 (symptom absent) to 4 (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful. | 6 weeks | 
| [MDD] Hamilton Depression Rating Scale (HAM-D) | The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of 0 (symptom absent) to 4 (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful. | 4 weeks post last day of treatment | 
| [Anxiety] Hamilton Anxiety Rating Scale (HAM-A) | The HAM-A is an observer/rater scale consisting of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | 6 weeks | 
| [Anxiety] Hamilton Anxiety Rating Scale (HAM-A) | The HAM-A is an observer/rater scale consisting of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | 4 weeks post last day of treatment | 
| [Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D | RBANS assesses immediate memory, visuospatial skill, language, attention, and delayed memory. Patient performance on each subscale immediate memory, language, attention, visuospatial, and delayed memory are scored relative to validated norms for same-aged peers. A change of 8+ points in the Total Scale score, 11+ points in the Immediate Memory score, 9+ points in the Language score, 4+ points on the Attention score, 14+ points is considered significant for the Visuospatial score, and 10+ points for the Delayed Memory score are considered significant. | 6 weeks | 
| [Dementia] Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D | RBANS assesses immediate memory, visuospatial skill, language, attention, and delayed memory. Patient performance on each subscale immediate memory, language, attention, visuospatial, and delayed memory are scored relative to validated norms for same-aged peers. A change of 8+ points in the Total Scale score, 11+ points in the Immediate Memory score, 9+ points in the Language score, 4+ points on the Attention score, 14+ points is considered significant for the Visuospatial score, and 10+ points for the Delayed Memory score are considered significant. | 4 weeks post last day of treatment | 
| [Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3 | The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status. | 6 weeks | 
| [Dementia] Montreal Cognitive Assessment (MoCA) versions 7.1-7.3 | The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status. | 4 weeks post last day of treatment | 
| [MDD] Beck Depression Inventory (BDI-II) | The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from 0 (this item does not apply) to 3 (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant. | 4 weeks post last day of treatment | 
| [Anxiety] Beck Anxiety Inventory (BAI) | The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of 0 (not at all) to 3 (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful. | 4 weeks post last day of treatment | 
| [Dementia] Quick Dementia Rating Scale (QDRS) | The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). | 4 weeks post last day of treatment | 
| [TBI] Brief Pain Inventory (BPI) | Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | 4 weeks post last day of treatment | 
| [All] Global Rating of Change (GRC) | The GRC consists of a single likert-scale ranging from -5 (very much worse) to 0 (neutral/no change) to 5 (very much better). The GRC is obtained in an interview format to assess a patient's perceived change in status following a treatment. A score that is at least 2 or greater is considered to indicate clinically significant change. | 4 weeks post last day of treatment |