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

Sponsor

Tanta University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05369793

Collaborator

(none)

Enrollment

Location

Arms

18.3

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes (Adult Onset) Diabetic Neuropathies	Drug: Alpha lipoic acid Drug: Roflumilast	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Sep 10, 2022

Anticipated Study Completion Date :

Dec 10, 2023

Arms and Interventions

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 glimepiride 1-4 mg 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 glimepiride 1-4 mg orally once daily for 3 months.

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 glimepiride 1-4 mg 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 glimepiride 1-4 mg orally once daily for 3 months.

Outcome Measures

Primary Outcome Measures

Change in fasting blood glucose [baseline 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 level [baseline and 3 months later]
Subtracting pre-treatment from post-treatment values of plasma insulin
Change in HOMA-IR index [baseline and 3 months later]
HOMA-IR will be calculated for all patients at baseline and 3 months later.
Change in HOMA-B index [baseline and 3 months later.]
HOMA-B will be calculated for all patients at baseline and 3 months later.
Change in HbA1c [baseline and 3 months later]
Subtracting pre-treatment from post-treatment values of HbA1C

Secondary Outcome Measures

Changes in TNF-alfa serum level [baseline and 3 months later]
Subtracting pre-treatment from post-treatment values of TNF-alfa.
Changes in malondialdehyde serum level (MDA) [baseline and 3 months later]
Subtracting pre-treatment from post-treatment values of MDA.
Changes in neurotensin serum levels [baseline and 3 months later]
Subtracting pre-treatment from post-treatment values of neurotensin serum levels.
Ewing score [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.
Changes of Michigan Neuropathy Screening Instrument [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.
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, )

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).