The Effect of High Intensity Interval Training and Surgical Weight Loss On Distal Symmetric Polyneuropathy Outcomes

高强度间歇训练和手术减肥对远端对称性多发性神经病结果的影响

基本信息

批准号：
9925079
负责人：
Brian Christopher Callaghan
金额：
$ 62.67万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-06 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925079
关键词：
Accounting Affect Age American Amputation Analgesics Behavior Body Weight decreased Clinic Counseling Cutaneous Data Diabetes Mellitus Diet Disease Distal Equilibrium Evaluation Exercise High Prevalence Impairment Individual Insulin-Dependent Diabetes Mellitus Interval training Intervention Intervention Trial Lead Life Link Lower Extremity Measures Medical Metabolic Metabolic syndrome Michigan Modeling Morbid Obesity Morbidity - disease rate Natural History Nerve Nerve Fibers Non-Insulin-Dependent Diabetes Mellitus Obesity Operative Surgical Procedures Outcome Outcome Study Pain Patient Recruitments Patients Pharmaceutical Preparations Polyneuropathy Population Prediabetes syndrome Prevalence Quality of life Randomized Regimen Review Committee Risk Risk Factors Risk Reduction Supervision Testing Therapeutic Thigh structure Time Ulcer Uncontrolled Study United States National Institutes of Health Universities Work bariatric surgery blood glucose regulation comparison group defined contribution density design dietary approach effective therapy epidemiology study exercise intervention exercise regimen falls group intervention improved innovation intervention effect nerve injury pain reduction painful neuropathy patient oriented phase 2 study phase II trial phase III trial prevent randomized trial recruit regenerative weight loss intervention

项目摘要

Project Summary/abstract Distal symmetric polyneuropathy (DSP) affects upwards of 15% of Americans over the age of 40. This highly prevalent condition impairs patient's quality of life, causes pain, and results in falls. Patients with DSP caused by diabetes are at particular risk for ulcerations and lower extremity amputations. Despite the large population affected by this disease and the significant morbidity that results, no disease modifying therapies exist to prevent nerve injury. Neuropathic pain medications can reduce the pain from DSP, but do not prevent nerve damage. Enhanced glucose control has been proven to prevent DSP in patients with type 1 diabetes, but has only a small effect on patients with type 2 diabetes. As a result, a critical need exists to develop disease modify therapies for patients with and at risk for DSP. We propose two potential disease modifying therapies, namely exercise and/or weight loss. To determine the impact of exercise on DSP outcomes, we plan to randomize patients to high intensity interval training (HIIT) or routine exercise counseling. We chose HIIT as our exercise regimen because of data supporting increased compliance in patients with obesity and diabetes. This innovative intervention also has emerging data to support improved metabolic outcomes in patients with diabetes. We hypothesize that exercise will have the largest effect on DSP outcomes because of three previous uncontrolled studies documenting substantial improvement in intraepidermal nerve fiber density and cutaneous regenerative capacity in those receiving an exercise regimen with little to no weight loss. By comparison, in an uncontrolled study, we found stable IENFD after two years of significant medical weight loss. While the natural history of IENFD is to decrease in those with diabetes and pre-diabetes, improvement in IENFD was not seen despite robust weight loss. We propose to determine the effect of weight loss on DSP outcomes by studying a bariatric surgery population where 55% of the patients have surgery once they are approved by the surgery review committee. We will stratify HIIT randomization 1:1 to those that do and those that do not undergo surgery. This non-randomized design will allow comparison of the effect of surgery to HIIT without the need for an expensive, randomized surgical intervention trial. Surgical weight loss may have a more robust effect on DSP outcomes than medical weight loss because of the magnitude and sustainability of weight loss. We will also be able to investigate the effect of combining surgical weight loss and HIIT. The proposed aims have the potential to identify promising exercise and/or weight loss interventions for DSP. This phase 2 study may lead to a definitive phase 3 trial, which would possibly result in the first disease modifying therapy for DSP. Given the high prevalence and substantial morbidity associated with DSP, such an intervention is desperately needed.

项目概要/摘要超过 15% 的 40 岁以上美国人患有远端对称性多发性神经病 (DSP)。这种流行病会损害患者的生活质量、引起疼痛并导致跌倒。 DSP引起的患者糖尿病患者特别容易发生溃疡和下肢截肢。尽管人口众多受这种疾病的影响以及由此导致的显着发病率，目前尚无疾病修饰疗法可以治疗防止神经损伤。神经性疼痛药物可以减轻 DSP 引起的疼痛，但不能阻止神经性疼痛损害。加强血糖控制已被证明可以预防 1 型糖尿病患者发生 DSP，但对2型糖尿病患者只有很小的影响。因此，迫切需要开发疾病修饰药物针对 DSP 患者和有 DSP 风险的患者的治疗。我们提出了两种潜在的疾病修饰疗法，即运动和/或减肥。确定运动对 DSP 结果的影响，我们计划将患者随机分组进行高强度间歇训练 (HIIT) 或日常运动咨询。我们选择 HIIT 作为我们的锻炼方案，因为数据支持增加肥胖和糖尿病患者的依从性。这项创新干预措施还提供了新数据支持改善糖尿病患者的代谢结果。我们假设运动会带来对 DSP 结果影响最大，因为之前三项非对照研究记录了大量接受治疗的患者表皮内神经纤维密度和皮肤再生能力得到改善运动疗法几乎没有减轻体重。相比之下，在一项非对照研究中，我们发现稳定的 IENFD 经过两年显着的医学减肥。虽然 IENFD 的自然史在这些中会减少对于糖尿病和糖尿病前期患者，尽管体重明显减轻，但 IENFD 并未见改善。我们建议通过研究减肥手术人群来确定减肥对 DSP 结果的影响，其中 55% 的患者一旦获得手术审查委员会的批准即可进行手术。我们将分层HIIT 接受手术和未接受手术的患者按 1:1 随机分组。这种非随机设计将无需进行昂贵的随机手术即可比较手术与 HIIT 的效果干预试验。手术减肥可能比医疗减肥对 DSP 结果产生更强烈的影响由于减肥的幅度和可持续性而导致的损失。我们还可以研究以下效果：结合手术减肥和 HIIT。拟议的目标有可能为 DSP 确定有前景的运动和/或减肥干预措施。这项 2 期研究可能会导致最终的 3 期试验，这可能会导致第一种疾病修改 DSP 治疗。鉴于 DSP 的高患病率和高发病率，迫切需要干预。