A 3-arm, Open-label, Stratified Randomized Controlled Trial with Blinded End-point Assessment to EValuate a Nitric OxidE Generator (Nebivolol) As a DiSease Modifying MediCatioN in Diabetic Peripheral Neuropathy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- The mean nerve action potential amplitude (sural and tibial nerves) between Arm 1 and Arm 3 at 24 weeks follow-up.
研究概览
简要总结
The goal of this clinical trial is to test in patients with diabetic neuropathy,
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Can Nevibolol at a dose of 2.5 mg- 10 mg compared with standard pain modulating treatment conserve the mean nerve action potential amplitude (sural and tibial nerves) at 24 weeks follow- up.
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Can Nevibolol at a dose of 2.5 mg- 10 mg compared with a combination of Alpha Lipoic Acid (600 mg/day)+EPALRESTAT (150 mg/day) conserve the mean nerve action potential amplitude (sural and tibial nerves) at 24 weeks follow- up
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All potential participants will undergo screening- about 10 ml of blood will be drawn to perform the following assesments at screening- HbA1c, FBS,Vit B12, TSH, fT4.
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Baseline assessments conducting a nerve conduction study, quality of life assesment using Eq-5D-5L and NRS pain score.
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20% of patients (24 patients) will undergo Sudoscan, Corneal confocal microscopy and a skin biopsy for assessing IENFD (Intra Epidermal Nerve Fibre Density).
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15th day, 1 month and 3rd month followup for evaluating patients status and medication adherance.
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6th month followup for evaluating patients status and medication adherance.
Researchers will compare Nebivolol against combination of Epalrestat+Alpha Lipoic Acid against standard pain modulating treatment to evaluate their diseaes modifying effect as reflected by nerve conduction study parameters.
详细描述
A 3 centre, 3-arm, parallel group, open label, stratified randomized controlled trial design is used with a 1:1:1 allocation ratio and blinding of outcome assessors.
Primary Objectives:
- To evaluate the efficacy of Tab. Nebivolol 10 mg/ day (or maximally tolerated dose) compared to standard care (pain modulators alone) on mean nerve action potential at week 24.
- To evaluate the efficacy of Tab. Nebivolol 10 mg/day (or maximally tolerated dose) compared to a combination of lipoic acid 600 mg/d plus epalrestat 150 mg/day at week 24 on mean nerve action potential at week 24.
Secondary Objectives: 1. To compare the intra-epidermal nerve fibre density (IENFD), high-sensitivity C-reactive protein (hsCRP) and quantify GAP-43 (neuromodulin) in a randomly selected sample (stratified by sex and baseline disease severity) of 20% patients from each from the 3 arms pre and post intervention: corneal nerve fiber length and density using confocal microscopy in all patients in the 3 arms at week 24.
- To compare the electrical conductance (mean µSiemens) using Sudoscan between the nebivolol arm versus standard care alone and the nebivolol arm versus alpha-lipoic acid plus epalrestat arm at week 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Trained outcomes assessor unaware of the treatment arm to which the patient has been allocated to will perform all outcomes assessments
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged >= 18 years diagnosed with diabetes mellitus, of a duration of <= 5 years since their diagnosis
- •HbA1c < 9 at enrolment with stable glycemic control for the last three months
- •Neuropathy meeting the following 'Toronto criteria' (8) - (a) abnormal nerve conduction study* based on age-matched controls at the site and - (b) a symptom or sign of neuropathy defined as one of either a diabetic neuropathy symptom score of >= 1/4 Or neuropathy disability score of >= 3/10 (9).
- •Abnormal NCS defined as one or more abnormal Z score in two or more nerves, based on sural nerve amplitude (antidromic stimulation), tibial and peroneal NCV, tibial amplitude, increased F-wave minimum latency (F-min), and absent F-waves (only considered abnormal in tibial nerve)
排除标准
- •Absolute contra-indications for nebivolol - sick-sinus syndrome, sinus bradycardia with a resting heart rate < 50/ minute, second or third degree AV-nodal blocks fascicular blocks, severe asthma or COPD and acute heart failure
- •Patients with a compelling indication for a non-dihydropyridine calcium channel blocker (CCB)
- •Patients with compelling need for another beta-blocker in the judgement of the treating team
- •Patients who have undergone major amputations of the lower limbs or are posted for the same.
研究组 & 干预措施
Nebivolol+ Standard care arm
This arm will receive tablet Nebivolol 2.5 mg OD uptitrated at 2 weeks to 5 mg and at 4 weeks if well tolerated to 10 mg/day which the participant will continue upto week 24
干预措施: Nebivolol+ Standard care arm (Drug)
Epalrestat + Alpha Lipoic Acid +Standard care
This arm will receive tablet Epalrestat -150mg OD+ cap Alpha Lipoic Acid 600mg OD for 24 weeks.
干预措施: Epalrestat + Alpha Lipoic Acid +Standard care (Drug)
Standard care alone
Patients in this arm will receive standard care as judged by their treating physicians which is generally pain modifying treatment.
干预措施: Standard care alone (Drug)
结局指标
主要结局
The mean nerve action potential amplitude (sural and tibial nerves) between Arm 1 and Arm 3 at 24 weeks follow-up.
时间窗: Baseline and 24 weeks
As part of nerve conduction study, the mean nerve action potential amplitude (sural and tibial nerves) will be compared between Arm 1 and Arm 3 at 24 weeks follow-up.
次要结局
- The proportion of patients who progress to develop severe neuropathy(Baseline and 24 weeks)