RecruitingPhase 2Phase 3NCT06201611

Evaluating a Nitric Oxide Generator, Nebivolol as a Disease Modifier in Patients With Diabetic Neuropathy.

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


Sponsor

St. John's Research Institute

Enrollment

120 participants

Start Date

Nov 15, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

The goal of this clinical trial is to test in patients with diabetic neuropathy, * 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. * 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 * 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. * Baseline assessments conducting a nerve conduction study, quality of life assesment using Eq-5D-5L and NRS pain score. * 20% of patients (24 patients) will undergo Sudoscan, Corneal confocal microscopy and a skin biopsy for assessing IENFD (Intra Epidermal Nerve Fibre Density). * 15th day, 1 month and 3rd month followup for evaluating patients status and medication adherance. * 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.


Eligibility

Max Age: 18 Years

Inclusion Criteria4

  • 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)

Exclusion Criteria4

  • 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.

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Interventions

DRUGNebivolol+ 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

DRUGEpalrestat + Alpha Lipoic Acid +Standard care

This arm will receive tablet Epalrestat -150mg OD+ cap Alpha Lipoic Acid 600mg OD for 24 weeks.

DRUGStandard care alone

Patients in this arm will receive standard care as judged by their treating physicians which is generally pain modifying treatment.


Locations(2)

St John's Medical College Hospital

Bangalore, Karnataka, India

St John's Research Institute

Bangalore, Karntakaka, India

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NCT06201611


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