Back to resultsClinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy
Primary Purpose
Type 2 Diabetes (Adult Onset), Diabetic Neuropathies
Status
Recruiting
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Alpha lipoic acid
Roflumilast
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes (Adult Onset) focused on measuring diabetes mellitus, diabetic neuropathy, hyperglycemia
Eligibility Criteria
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).
Sites / Locations
- Asmaa Elshafey ElsharabRecruiting
- Asmaa Elshafey Elsharab
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Alpha-lipoic acid arm
Roflumilast arm
Arm Description
Administration of alpha-lipoic acid 600 mg orally once daily for 3 months.
Administration of roflumilast 500 mcg orally once daily for 3 months.
Outcomes
Primary Outcome Measures
Change in fasting blood glucose
Using glucose oxidase method for assessment of blood glucose and subtracting pre-treatment from post-treatment values
Change in plasma insulin level
Subtracting pre-treatment from post-treatment values of plasma insulin
Change in HOMA-IR index
HOMA-IR will be calculated for all patients at baseline and 3 months later.
Change in HOMA-B index
HOMA-B will be calculated for all patients at baseline and 3 months later.
Change in HbA1c
Subtracting pre-treatment from post-treatment values of HbA1C
Secondary Outcome Measures
Changes in TNF-alfa serum level
Subtracting pre-treatment from post-treatment values of TNF-alfa.
Changes in malondialdehyde serum level (MDA)
Subtracting pre-treatment from post-treatment values of MDA.
Changes in neurotensin serum levels
Subtracting pre-treatment from post-treatment values of neurotensin serum levels.
Ewing score
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
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)
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)
DN4 Neuropathic Pain Diagnostic Questionnaire which reflect positive symptoms for pain ( burning, painful cold, electric shocks, )
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05369793
Brief Title
Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy
Official Title
Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
September 10, 2023 (Anticipated)
Study Completion Date
December 10, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes (Adult Onset), Diabetic Neuropathies
Keywords
diabetes mellitus, diabetic neuropathy, hyperglycemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Alpha-lipoic acid arm
Arm Type
Active Comparator
Arm Description
Administration of alpha-lipoic acid 600 mg orally once daily for 3 months.
Arm Title
Roflumilast arm
Arm Type
Experimental
Arm Description
Administration of roflumilast 500 mcg orally once daily for 3 months.
Intervention Type
Drug
Intervention Name(s)
Alpha lipoic acid
Intervention Description
Administration of alpha-lipoic acid 600mg plus vildagliptin/metformin combination (50/1000mg) orally once daily for 3 months.
Intervention Type
Drug
Intervention Name(s)
Roflumilast
Intervention Description
Administration of 500 mcg plus vildagliptin/metformin combination(50/1000mg) orally once daily for 3 months.
Primary Outcome Measure Information:
Title
Change in fasting blood glucose
Description
Using glucose oxidase method for assessment of blood glucose and subtracting pre-treatment from post-treatment values
Time Frame
baseline and 3 months later
Title
Change in plasma insulin level
Description
Subtracting pre-treatment from post-treatment values of plasma insulin
Time Frame
baseline and 3 months later
Title
Change in HOMA-IR index
Description
HOMA-IR will be calculated for all patients at baseline and 3 months later.
Time Frame
baseline and 3 months later
Title
Change in HOMA-B index
Description
HOMA-B will be calculated for all patients at baseline and 3 months later.
Time Frame
baseline and 3 months later.
Title
Change in HbA1c
Description
Subtracting pre-treatment from post-treatment values of HbA1C
Time Frame
baseline and 3 months later
Secondary Outcome Measure Information:
Title
Changes in TNF-alfa serum level
Description
Subtracting pre-treatment from post-treatment values of TNF-alfa.
Time Frame
baseline and 3 months later
Title
Changes in malondialdehyde serum level (MDA)
Description
Subtracting pre-treatment from post-treatment values of MDA.
Time Frame
baseline and 3 months later
Title
Changes in neurotensin serum levels
Description
Subtracting pre-treatment from post-treatment values of neurotensin serum levels.
Time Frame
baseline and 3 months later
Title
Ewing score
Description
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.
Time Frame
baseline and 3 months later
Title
Changes of Michigan Neuropathy Screening Instrument
Description
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.
Time Frame
baseline and 3 months later
Title
Changes of Michigan Neuropathy Screening Instrument(MNSIE)
Description
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.
Time Frame
baseline and 3 months later
Title
Changes of Douleur Neuropathique-4 (DN4) questionnaire (DN4)
Description
DN4 Neuropathic Pain Diagnostic Questionnaire which reflect positive symptoms for pain ( burning, painful cold, electric shocks, )
Time Frame
baseline and 3 months later
Other Pre-specified Outcome Measures:
Title
Assessment of changes in patients' quality of life
Description
Using Diabetes Quality Of Life questionnaire (DQOL)
Time Frame
baseline and 3 months later
Title
Major adverse cardiovascular events (MACE)
Description
Major adverse cardiovascular events (MACE) as non-fatal myocardial infarction (MI), non-fatal stroke, and cardiovascular death.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Facility Information:
Facility Name
Asmaa Elshafey Elsharab
City
Tanta
ZIP/Postal Code
31511
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asmaa E Elsharab, Pharm D
Phone
00201151989876
Email
asmaa94.elshafey@gmail.com
First Name & Middle Initial & Last Name & Degree
Asmaa E Elsharab, Pharm D
Facility Name
Asmaa Elshafey Elsharab
City
Tanta
ZIP/Postal Code
31511
Country
Egypt
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asmaa E Elsharab, Pharm D
Phone
00201151989876
Email
asmaa94.elshafey@gmail.com
First Name & Middle Initial & Last Name & Degree
Asmaa E Elsharab, Pharm D
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Clinical Study Evaluating the Safety and Efficacy of Roflumilast in Type 2 Diabetic Patients With Diabetic Neuropathy
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