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

NCT06201611 | Recruiting Phase 2

• 1 other identifier: IEC/1/1218/2023
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Diabetic Neuropathy Peripheral

Outcome Measures

Primary Outcomes (1)

• The mean nerve action potential amplitude (sural and tibial nerves) between Arm 1 and Arm 3 at 24 weeks follow-up.

  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.

  Baseline and 24 weeks

Secondary Outcomes (1)

• The proportion of patients who progress to develop severe neuropathy

  Baseline and 24 weeks

Study Arms (3)

Nebivolol+ Standard care arm

EXPERIMENTAL

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

Drug: Nebivolol+ Standard care arm

Epalrestat + Alpha Lipoic Acid +Standard care

ACTIVE COMPARATOR

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

Drug: Epalrestat + Alpha Lipoic Acid +Standard care

Standard care alone

ACTIVE COMPARATOR

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

Drug: Standard care alone

Interventions

Nebivolol+ Standard care arm DRUG

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

Nebivolol+ Standard care arm

Epalrestat + Alpha Lipoic Acid +Standard care DRUG

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

Epalrestat + Alpha Lipoic Acid +Standard care

Standard care alone DRUG

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

Standard care alone

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. John's Research Institute: lead

Study Sites (2)

St John's Medical College Hospital

Bangalore, Karnataka, 560034, India

RECRUITING

St John's Research Institute

Bangalore, Karntakaka, 560034, India

NOT YET RECRUITING

MeSH Terms

Interventions

epalrestat

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Trained outcomes assessor unaware of the treatment arm to which the patient has been allocated to will perform all outcomes assessments
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will use a 3 center, 3-arm, parallel group, open label, stratified randomized controlled trial design with a 1:1:1 allocation ratio and blinding of outcome assessors.

Study Record Dates

• First Submitted: December 30, 2023
• First Posted: January 11, 2024
• Study Start: November 15, 2024
• Primary Completion: December 30, 2025
• Study Completion: March 30, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 3 years after database lock indefinitely.

Locations

IN (2)