Use of a novel physiologic measure for the assessment and monitoring of vincristine induced peripheral neuropathy (VIPN) in children and adolescents.

使用一种新的生理测量方法来评估和监测儿童和青少年长春新碱引起的周围神经病变（VIPN）。

• 批准号: 10547068
• 负责人: Julia Cole Finkel
• 金额: $ 39.67万
• 依托单位: ALGOMETRX, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10547068
• 关键词: 6 year old; Acute Lymphocytic Leukemia; Adolescent; Adult; Affect; Aftercare; Age; Amyloid beta-Protein; Assessment tool; Axonal Transport; Child; Childhood; Chronic; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Collaborations; Common Terminology Criteria for Adverse Events; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Dose; Early Diagnosis; Early Intervention; Electric Stimulation; Enrollment; Fiber; Goals; Hospitals; Immunotherapy; Individual; Life; Maintenance; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Medical Device; Microtubules; Monitor; Morbidity - disease rate; Motor; Muscle Weakness; Nerve Fibers; Neuropathy; Nociception; Numbness; Painless; Participant; Pathway interactions; Patient Self-Report; Patients; Performance; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Phase; Physiological; Population; Prevalence; Process; Public Health; Pupil; Quality of life; Reflex action; Reporting; Research; Risk Factors; Schedule; Sensory; Severities; Stimulus; Survival Rate; Survivors; Symptoms; Techniques; Technology; Testing; Time; Treatment Protocols; Upper Extremity; Validation; Vincristine; afferent nerve; chemotherapy; clinical care; holistic approach; improved; indexing; innovation; meetings; neurotoxicity; new technology; novel; novel strategies; painful neuropathy; pediatric patients; prevent; prototype; research study; response; risk minimization; standard of care; tool

In this application, we propose the examination of a novel physiologic measure of vincristine-induced peripheral neuropathy (VIPN) in pediatric patients. Establishment of such a measure will enable the objective characterization of both the positive and negative symptoms of neuropathy in pediatric patients treated with vincristine in order to enable early detection and management of the resulting morbidity. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer but has a 90% 5-year survival rate in children due to current treatment protocols, of which vincristine is a critical component. Vincristine induces primarily a large fiber peripheral neuropathy by disrupting microtubule associated axonal transport. Clinically, this manifests as muscle weakness, loss of reflexes, neuropathic pain and loss of sensation. Clinical assessments and research of the prevalence and risk factors for vincristine neurotoxicity have been hampered by the differing sensitivities of neuropathy assessment tools. VIPN often manifests during treatment but can be present for years following therapy leading to a diminished quality of life. It is therefore imperative to develop a clinical tool to detect VIPN before the onset of overt symptoms. In this proposal, we define and assess a metric of VIPN, the Neuropathy Index, informed by a novel technology that can produce an objective assessment of nerve fiber sensitivity. This technology leverages our transformative finding that an innocuous, transcutaneous neuroselective electrical stimulus of each sensory nerve fiber type (C, Aδ and Aβ) induces a pupillary dilation (nPRD) response reflecting the sensitivity of the fiber. The nPRD responses of the three fiber types are compared to generate a composite index, Neuropathy Index, that will be used for the assessment of VIPN. To accomplish this, we propose the following aim: Aim 1: Assess the performance of a novel physiologic endpoint, the Neuropathy Index, for the characterization of nociceptive processing in patients with VIPN. We plan to enroll 20 patients ages 6y-18y diagnosed with ALL and receiving (or scheduled to receive) vincristine. We plan to collect data at regular intervals over the course of 8 months, which will allow us to measure different levels of VIPN severity. Participants will also be evaluated using the TNS©-PV. Using this approach, we plan to apply the Neuropathy Index (i.e., [AUCAδ-AUCAβ]/AUCC) to the data collected during each testing session. We then plan to compare the Neuropathy Index to the TNS-PV to determine the relationship between these two measures. We also plan to assess the reliability of the index via a test/retest paradigm and assess the patient reported acceptability of our test compared to that of the TNS-PV. Milestone: Demonstration of a relationship between the Index and the TNS-PV (a correlation of at least 0.7) and of reliability (a test- retest reliability coefficient of at least 0.58). Ultimately, the technology being developed in this application would enable early detection of VIPN, optimizing vincristine dosing for maximum disease response and early intervention with the goal of minimizing the risk of chronic functional deficits.

在这个应用中，我们提出了一种新的长春新碱诱导的生理测量方法