Far Red Light to Improve Functioning in PAD

Study Overview
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Brief Summary
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The LIGHT PAD Trial is a Phase II multi-centered randomized clinical trial to collect preliminary data to test whether daily far red light treatment of the lower extremities in people with PAD improves six-minute walk distance, lower extremity perfusion, and ischemia-related damage in gastrocnemius muscle at four-month follow-up, compared to a sham control. Participants will complete 10 minutes of twice daily home treatment with either far red light or a sham light for four months.

Detailed Description
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The LIGHT PAD Trial is a Phase II multi-centered randomized clinical trial to collect preliminary data to test whether daily far red light treatment of the lower extremities in people with PAD improves six-minute walk distance, lower extremity perfusion, and ischemia-related damage in gastrocnemius muscle at four-month follow-up, compared to a sham control. Participants will complete 10 minutes of twice daily home treatment with either far red light or a sham light for four months. Participants with PAD will be randomized at one of two centers: Northwestern University (PI: MM McDermott, MD) and the University of Alabama (PI: Nicole Lohr MD, PhD) to daily far red light or sham control for four months. The primary outcome, change in six-minute walk, will be measured at four month follow-up, immediately after the final administration of far red light or sham. In secondary and exploratory aims, investigators will distinguish between acute and chronic effects of far red light on six-minute walk, measure the effects of far red light on patient-reported outcomes, and delineate biologic pathways by which far red light improves walking performance in PAD, by measuring change in plasma nitrite and nitrosothiols, gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health and mitochondrial activity. If the proposed hypotheses are supported by this Phase II trial, results will be used to design a definitive randomized trial of far red light for people with PAD. To achieve the specific aims, investigators will randomize 32 participants age 50 and older with PAD to one of two groups: far red light therapy or sham therapy. Participants will be followed for four months.

Official Title
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Far Red Light to Improve Functioning in PAD: The LIGHT PAD Trial

Conditions
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Peripheral Artery Disease, Peripheral Vascular Disease, Aging, Walking, Difficulty

Intervention / Treatment
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* Device: Far red light therapy
* Device: Sham light therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria. First, all participants will be age 50 and older. Second, all participants will have PAD. PAD will be defined as: An ABI < 0.90 at baseline. Vascular lab evidence of PAD (such as a toe brachial pressure < 0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities. An ABI of >0.90 and <1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test. Exclusion Criteria: Above- or below-knee amputation Critical limb ischemia defined as an ABI <0.30 or <0.40 with symptoms of rest pain Wheelchair confinement or requiring a walker to ambulate Walking is limited by a symptom other than PAD Current foot ulcer on bottom of foot Failure to successfully complete the study run-in Planned major surgery, coronary or leg revascularization during the next four months Major surgery, coronary or leg revascularization or major cardiovascular event in the previous three months Major medical illness including lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. [NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent, unless the cancer is located in the lower extremities. Participants who require oxygen only at night may still qualify.] Mini-Mental Status Examination (MMSE) score < 23 Non-English speaking Participation in or completion of a clinical trial in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.] Visual impairment that limits walking ability. Six-minute walk distance of <400 feet or >1700 feet. Participation in a supervised treadmill exercise program or a cardiac rehabilitation program in previous three months or planning to begin a supervised treadmill exercise program or a cardiac rehabilitation program in the next five months. Unwilling to avoid red light therapy outside of study participation. Baseline blood pressure <100/45. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Investigators will randomize 32 participants age 50 and older with PAD to one of two groups: far red light therapy or sham therapy. Participants will be followed for four months.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Far red light therapy<br>Subgroup of participants receiving the 670 nm far red light device | Device: Far red light therapy<br>* All participants will receive one far red light device per leg. Participants will be asked to use their two light devices daily, exposing their bare legs to the devices for 10 minutes twice per day. An unblinded study coordinator will deliver the light devices to each participant's home, positioning the devices 15 cm behind the participant's heels, using tape on the floor to mark where the light and feet should be positioned. Twice each day, the participant flips a switch on the device to begin each session. A timer will turn off the device after 10 minutes. A power meter will measure the total time that the device was turned on. Participants will also record use of the light in a log.<br>|
| Sham Comparator: Sham therapy<br>Subgroup of participants receiving the sham light device, far red light device covered with blue filter paper to block 670 nm light, resulting in mean power generated of 0.24 mW/cm2, compared to 26.3 mW/cm2 for the intervention, a 100-fold difference. | Device: Sham light therapy<br>* All participants will receive one sham device per leg. Participants will be asked to use their two light devices daily, exposing their bare legs to the devices for 10 minutes twice per day. An unblinded study coordinator will deliver the light devices to each participant's home, positioning the devices 15 cm behind the participant's heels, using tape on the floor to mark where the light and feet should be positioned. Twice each day, the participant flips a switch on the device to begin each session. A timer will turn off the device after 10 minutes. A power meter will measure the total time that the device was turned on. Participants will also record use of the light in a log.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-Minute Walk Distance | Change in six-minute walk distance | Measured at baseline and 4 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking Impairment Questionnaire Distance Score | Participant report of difficulty walking increasingly longer distances. Score range 0-100, 100 is best | Measured at baseline and 4 month follow-up | 
| Six-Minute Walk Distance | Change in six-minute walk distance | Measured immediately after the first light treatment (within 15 minutes after the first treatment, acute effect) | 
| Six-minute walk distance. | The distance walked in six minutes (chronic) | Measured at 4-month follow-up, 24 hours after the final treatment. | 
| Gastrocnemius Perfusion | Changes in calf perfusion at 3 Tesla measured with arterial spin labeling with MRI and post-cuff occlusion hyperemia | Measured at baseline and four-month follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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light therapy