A pilot clinical study to evaluate the use of photobiomodulation in patients with dry age-related macular degeneration

一项评估光生物调节在干性年龄相关性黄斑变性患者中的应用的初步临床研究

• 批准号: 8903271
• 负责人: CLARK E TEDFORD
• 金额: $ 25.6万
• 依托单位: LUMITHERA, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8903271
• 关键词: Acute; Address; Aftercare; Age; Age related macular degeneration; Angiography; Anterior Ischemic Optic Neuropathy; Applications Grants; Area; Blindness; Cells; Chronic; Chronic Disease; Clinical; Clinical Data; Clinical Research; Clinical Trials; Code; Color; Contrast Sensitivity; Data; Developed Countries; Development; Diabetic Retinopathy; Disease; Disease Progression; Dose; Drusen; Effectiveness; Elderly; Engineering; Enrollment; Ensure; Etiology; Exudative age-related macular degeneration; Foundations; Healthcare Systems; Human; Image; Impairment; Inflammation; Label; Lasers; Lead; Leber' s Hereditary Optic Neuropathy; Life; Maps; Marketing; Masks; Measurement; Medical; Medical Device; Medicine; Metabolic; Mitochondria; Molecular Target; Ophthalmologist; Outcome Measure; Oxidative Stress; Patient Recruitments; Patients; Phototherapy; Placebos; Population; Preventive; Property; Randomized Clinical Trials; Research; Research Personnel; Resources; Retinal; Risk; Safety; Scanning; Serious Adverse Event; Small Business Innovation Research Grant; Specialist; Staging; Thick; Time; Treatment Protocols; Universities; Vascular Endothelial Growth Factors; Venous; Vision; Visual Acuity; age related; base; biological systems; clinical application; commercialization; cost; design; experience; follow-up; instrument; macula; member; meter; mitochondrial dysfunction; new therapeutic target; novel; photobiomodulation; prospective; prototype; public health relevance; restorative treatment; tomography

 DESCRIPTION (provided by applicant): As the population continues to age, degenerative ocular diseases become increasingly common and create tremendous burden on the health care system. Vision impairment in the elderly with AMD takes away an average of 5 quality years of life. Age-related macular degeneration (AMD) represents a large market with ~2 million patients and another ~8 million people at risk in the U.S. alone. Approximately, 90% of the AMD patients have the "dry" form of the disease. There are no approved treatments for dry AMD and, thus it represents a potential high impact, targeted area in medicine. A investigator study lead by Drs. Merry and Dotson from The Toronto and Oak Ridge Study of Photobiomodulation (TORPA) looked at the effect of low level light therapy (LLLT) in the treatment of dry AMD. The TORPA data for dry AMD shows clinically and statistically significant improvement in visual acuity and contrast sensitivity, immediately after treatment for 6 weeks, demonstrating the potential use of LLLT in dry-AMD. The TORPA study combined multiple pre-selected wavelengths to stimulate mitochondrial CCO function and suppress VEGF expression. The study conclusions were that LED treatment was a non- invasive, easily administered and safe treatment with no serious adverse events noted. More importantly, the study provides the only 1 year follow-up data of LED effectiveness in dry AMD. These findings are the first to demonstrate a statistically significant clinical benefit (F(4,68) = 18.86, p < 0.0001) at up to 1 yr in dry AMD patients with LLLT. LumiThera was formed from founders with extensive clinical and developmental expertise in photobiomodulation to lead in the commercialization efforts. Multiple wavelength LED clinical and prototype commercial instruments are being designed and built for an ophthalmologist office-based setting. The current SBIR proposal is to conduct a pilot prospective, double-masked clinical trial with LumiThera's ophthalmological designed LED instrument, LT-300. Specific Aim 1 will establish the magnitude of clinical and OCT imaging benefit of multiple LED wavelengths on 20 dry AMD patients, divided into two groups. Approximately 10 subjects will be treated in group 1, and approximately 10 subjects will be given a sham treatment in group 2 over a three-week period (3 times per week for 3). LED Treatments will be administered by Dr. Merry, masked to the outcome measures. Drs Devenyi and Markowitz (University of Toronto) will act as co-investigators and provide patient recruitment, review all clinical data and AEs and imaging scans. All subjects will undergo Retinal Specialist assessment, Ocular Coherence Tomography (OCT) and Intra-venous Fluoroscein Angiography (IVFA) prior to enrollment to ensure non-neovascular AMD. All subjects are assessed with ETDRS logMAR Visual Acuity at 4 meters, contrast sensitivity at 1.5 and 3 cycles per degree. Clinical and OCT Measurements will take place prior to treatment, immediately following the treatment protocol (3 weeks), 3, 6, 12 months after. The findings will provide the basic safety and scientific foundation for a pivotal trial with a novel non- invasive, non-pharmaceutical therapy for dry-AMD.

 描述(申请人提供)：随着人口继续老龄化，退行性眼部疾病变得越来越常见，给医疗保健系统带来了巨大的负担。老年性黄斑变性患者视力受损平均夺去5年的生命质量。老年性黄斑变性(AMD)是一个巨大的市场，仅在美国就有约200万患者和约800万人面临风险。大约90%的AMD患者患有干燥型AMD。目前还没有针对干性AMD的已获批准的治疗方法，因此它在医学上是一个潜在的高影响靶向领域。多伦多和橡树岭光生物调节研究(TORPA)的Merry和Dotson博士领导的一项研究着眼于弱光疗法(LLLT)在治疗干性AMD中的作用。干性AMD患者的TORPA数据显示，在治疗6周后，干性AMD患者的视力和对比敏感度在临床和统计学上有显著改善，证明了LLLT在干性AMD中的潜在应用。TORPA研究结合了多个预先选择的波长来刺激线粒体CCO功能并抑制血管内皮生长因子的表达。研究结论是，LED治疗是一种非侵入性、易于管理和安全的治疗方法，没有严重的不良反应。更重要的是，这项研究提供了LED在干性AMD中有效性的唯一一年随访数据。这些发现首次证明了干性老年性黄斑变性在一年内有统计学意义的临床益处(F(4，68)=18.86p&lt；0.0001 LLLT患者。LumiThera是由在光生物调节方面拥有广泛的临床和开发专业知识的创始人组成的，以领导商业化努力。多波长LED临床和原型商业仪器正在为眼科医生办公室环境而设计和制造。目前的SBIR建议是使用LumiThera的眼科设计的LED仪器LT-300进行一项试验性的前瞻性、双掩蔽临床试验。具体目标1将在20名干性AMD患者中建立多个LED波长的临床和OCT成像益处的大小，将其分为两组。第一组大约10名受试者将接受治疗，第二组大约10名受试者将接受为期三周的假治疗(每周3次，共3次)。LED治疗将由梅里博士实施，并对结果进行评估。DRS Devenyi和Markowitz(多伦多大学)将担任联合调查员，提供患者招募、审查所有临床数据和AEs和成像扫描。所有受试者将在登记前接受视网膜专家评估、眼部相干断层扫描(OCT)和静脉内荧光素血管成像(IVFA)，以确保非新生血管性AMD。所有受试者在4米处进行ETDRS logMAR视力评估，对比敏感度在1.5度，每度3个循环。临床和OCT测量将在治疗前、治疗方案后立即(3周)、3、6、12个月后进行。这些发现将为一项针对干性AMD的新的非侵入性、非药物疗法的关键试验提供基本的安全性和科学基础。