Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy

November 20, 2023 updated by: Asmaa Elshafey Elsharab, Tanta University
Evaluation of the side effects and efficacy of roflumilast on glycemic parameters, insulin resistance, oxidative and inflammatory markers in Type 2 diabetic patients with diabetic neuropathy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Tanta, Egypt, 31511
        • Asmaa Elshafey Elsharab

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with a diagnosis of type 2 diabetes mellitus (T2DM).
  • HbA1c at baseline: ≥7.5 % to 8.5 %.
  • BMI between ≥26 and ≤35 kg/ m2.
  • Established Diabetic neuropathy diagnosed by nerve conduction study (NCS).

Exclusion Criteria:

  • Patients diagnosed with type 1 diabetes mellitus or diabetes secondary to pancreatitis or resection of the pancreas.
  • Patients diagnosed with hemoglobinopathies, hemolytic anemia, or other diseases which interfere with HbA1c measurement.
  • Thyroid disease, cardiovascular disease, peripheral vascular disease, coagulopathy, moderate to severe liver disease (bilirubin>1.5mg), or renal excretion ≤90ml/min.
  • Patients on medications which can result in a change of weight (orlistat, metformin, clozapine, gabapentin) and patients on medications that can interfere with glucose or lipid metabolism (corticosteroids, non-selective β-blockers, thiazides, etc.)
  • Treatment with any diabetes medications other than glimepiride prior to intervention.
  • Clinically significant cardiac abnormalities (diagnosed clinically, history, or by X-ray/ECG) that were not related to type 2 diabetes mellitus and that required further evaluation.
  • Patients with morbid obesity (BMI ≥ 40 kg/ m2).
  • History or current diagnosis of major depressive disorders or other psychiatric disorders.
  • Pregnant and breastfeeding women.
  • Patients with any inflammatory diseases.
  • Patients on cytochrome P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, etc.).
  • Patients with Low vitamin B12 levels according to suggested normal values for T2DM patients over 60 years old (<400 pmol/L).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Alpha-lipoic acid arm
Administration of alpha-lipoic acid 600 mg orally once daily for 3 months.
Drug: Alpha lipoic acid
Administration of alpha-lipoic acid 600mg plus vildagliptin/metformin combination (50/1000mg) orally once daily for 3 months.
Experimental: Roflumilast arm
Administration of roflumilast 500 mcg orally once daily for 3 months.
Drug: Roflumilast
Administration of 500 mcg plus vildagliptin/metformin combination(50/1000mg) orally once daily for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in fasting blood glucose
Time Frame: baseline and 3 months later
Using glucose oxidase method for assessment of blood glucose and subtracting pre-treatment from post-treatment values
baseline and 3 months later
Change in plasma insulin level
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment values of plasma insulin
baseline and 3 months later
Change in HOMA-IR index
Time Frame: baseline and 3 months later
HOMA-IR will be calculated for all patients at baseline and 3 months later.
baseline and 3 months later
Change in HOMA-B index
Time Frame: baseline and 3 months later.
HOMA-B will be calculated for all patients at baseline and 3 months later.
baseline and 3 months later.
Change in HbA1c
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment values of HbA1C
baseline and 3 months later

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in TNF-alfa serum level
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment values of TNF-alfa.
baseline and 3 months later
Changes in malondialdehyde serum level (MDA)
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment values of MDA.
baseline and 3 months later
Changes in neurotensin serum levels
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment values of neurotensin serum levels.
baseline and 3 months later
Ewing score
Time Frame: baseline and 3 months later
Subtracting pre-treatment from post-treatment changes in summation of the cardiac autonomic reflex tests (CARTs) including heart response to a deep breathing test, changes in immediate heart rate response to standing, and changes in blood pressure response to sustained handgrip testing.
baseline and 3 months later
Changes of Michigan Neuropathy Screening Instrument
Time Frame: baseline and 3 months later

A 15-item questionnaire (MNSIQ) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.

MNSIQ was designed to screen for diabetic neuropathy through questionnaires on 15 questions that are related to neuropathic symptoms (pain, temperature, and sensation). Two of 15 (number 4 and 10) are vascular symptoms and are excluded from the total score regardless of the results. If you answered 'No' to questions 7 and 13, you will get 1 point. In the end, scores ranging from 0 to 13 indicate that the higher the score, the more severe the neuropathic symptoms.
baseline and 3 months later
Changes of Michigan Neuropathy Screening Instrument(MNSIE)
Time Frame: baseline and 3 months later

A foot test (MNSIE) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers.

MNSIE evaluates foot shape, foot ulceration, ankle reflex, sense of vibration of big toe, monofilament right and left. The score ranges from point 0 to 10, and when the score is above 2, it is diagnosed as neuropathy.
baseline and 3 months later
Changes of Douleur Neuropathique-4 (DN4) questionnaire (DN4)
Time Frame: baseline and 3 months later
DN4 Neuropathic Pain Diagnostic Questionnaire which reflect positive symptoms for pain ( burning, painful cold, electric shocks, )
baseline and 3 months later

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of changes in patients' quality of life
Time Frame: baseline and 3 months later
Using Diabetes Quality Of Life questionnaire (DQOL)
baseline and 3 months later
Major adverse cardiovascular events (MACE)
Time Frame: 3 months
Major adverse cardiovascular events (MACE) as non-fatal myocardial infarction (MI), non-fatal stroke, and cardiovascular death.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2022

Primary Completion (Actual)

October 10, 2023

Study Completion (Actual)

October 10, 2023

Study Registration Dates

First Submitted

May 6, 2022

First Submitted That Met QC Criteria

May 6, 2022

First Posted (Actual)

May 11, 2022

Study Record Updates

Last Update Posted (Estimated)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 35420/4/22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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