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

Phase 3
Completed
Conditions
Type 2 Diabetes (Adult Onset)
Diabetic Neuropathies
Interventions
Registration Number
NCT05369793
Lead Sponsor
Tanta University
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Alpha-lipoic acid armAlpha lipoic acidAdministration of alpha-lipoic acid 600 mg orally once daily for 3 months.
Roflumilast armRoflumilastAdministration of roflumilast 500 mcg orally once daily for 3 months.
Primary Outcome Measures
NameTimeMethod
Change in HOMA-B indexbaseline and 3 months later.

HOMA-B will be calculated for all patients at baseline and 3 months later.

Change in fasting blood glucosebaseline and 3 months later

Using glucose oxidase method for assessment of blood glucose and subtracting pre-treatment from post-treatment values

Change in plasma insulin levelbaseline and 3 months later

Subtracting pre-treatment from post-treatment values of plasma insulin

Change in HOMA-IR indexbaseline and 3 months later

HOMA-IR will be calculated for all patients at baseline and 3 months later.

Change in HbA1cbaseline and 3 months later

Subtracting pre-treatment from post-treatment values of HbA1C

Secondary Outcome Measures
NameTimeMethod
Changes in malondialdehyde serum level (MDA)baseline and 3 months later

Subtracting pre-treatment from post-treatment values of MDA.

Changes in neurotensin serum levelsbaseline and 3 months later

Subtracting pre-treatment from post-treatment values of neurotensin serum levels.

Changes of Michigan Neuropathy Screening Instrument(MNSIE)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.

Changes of Douleur Neuropathique-4 (DN4) questionnaire (DN4)baseline and 3 months later

DN4 Neuropathic Pain Diagnostic Questionnaire which reflect positive symptoms for pain ( burning, painful cold, electric shocks, )

Changes in TNF-alfa serum levelbaseline and 3 months later

Subtracting pre-treatment from post-treatment values of TNF-alfa.

Ewing scorebaseline 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.

Changes of Michigan Neuropathy Screening Instrumentbaseline 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.

Trial Locations

Locations (1)

Asmaa Elshafey Elsharab

🇪🇬

Tanta, Egypt

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