Liver Cirrhosis With Diabetes
Conditions
Keywords
Liver Cirrhosis, Diabetes, Sitagliptin, Duloxetine
Brief summary
This study was a prospective, interventional, two-part pilot clinical study conducted over 3 months on cirrhotic patients with diabetes mellitus and diabetic neuropathy, evaluating the real-world applicability of selected PBPK-guided dosing regimens. Patients were stratified according to Child-Pugh class (CP-A , CP-B, and CP-C) in case of sitagliptin and CP-A in duloxetine at doses corresponding to the closest commercially available strengths to Simcyp®-optimized doses. Clinical evaluation included glycemic parameters(HbA1C,fasting blood glucose,2-hr post prandial glucose level) and pain reduction. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\],and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]),and CBC.
Detailed description
This study was a prospective, interventional, two-part pilot clinical study conducted over 3 months on Egyptian cirrhotic patients with diabetes mellitus and diabetic neuropathy. Adult patients aged \>18 years with confirmed liver cirrhosis, concomitant diabetes mellitus and diabetic neuropathy were eligible for inclusion. Patients were experienced acute episodes of disease associated with deterioration of hepatic function within 2 months prior to screening, and received concomitant medications known to strongly interact with the study drugs were excluded. In part 1: Sitagliptin dosing was determined based on Simcyp -generated predictions and clinical assessment. 100mg,100 mg, 50 mg, and 50 mg received by control, CP-A, CP-B, and CP-C cirrhosis patients, respectively, orally once daily. In part 2: Duloxetine dosing was determined based on Simcyp-generated predictions and clinical assessment. 60 mg ,30 mg received by control, and CP-A cirrhotic patients orally once daily, respectively. Clinical evaluation included glycemic parameters(HbA1C,fasting blood glucose,2-hr post prandial glucose level) and pain reduction. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\],and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]),and CBC.
Interventions
Diabetic patients with Child-Pugh class A hepatic cirrhosis receiving 100 mg model -informed adjusted dose of sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.
Diabetic patients with Child-Pugh class C hepatic cirrhosis receiving 50 mg model -informed adjusted dose of sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.
Diabetic patients without hepatic cirrhosis receiving the standard recommended dose of 60 mg Duloxetine. Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor, It has since received approval for a variety of indications including the treatment of neuropathic pain.
DRUGDuloxetine 30mg once daily
Diabetic patients with peripheral diabetic neuropathy and Child-Pugh class A hepatic cirrhosis receiving 30 mg model -informed adjusted dose of duloxetine. Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor, It has since received approval for a variety of indications including the treatment of neuropathic pain.
Sponsors
Kafrelsheikh University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Parallel-assignment interventional study to compare dose-adjusted \[Drug name\] across Child-Pugh classes with standard-dose diabetic controls."
Intervention model description
Parallel-assignment interventional study to compare dose-adjusted sitagliptin and duloxetine across Child-Pugh classes with standard-dose diabetic controls."
Eligibility
Sex/Gender
ALL
Age
18 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Clinical diagnosis of cirrhosis. * Diagnosed with diabetes mellitus. * Presence of diabetic neuropathy. * Age of patients \> 18 years.
Exclusion criteria
* Patients with kidney disorder or dialysis * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Management of diabetes mellitus and diabetic neuropathy | 3 months | by measuring glycemic parameters ( fasting blood glucose level,2-hr postprandial glucose level) (mg/dL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Effects Monitoring | 3 months | Adverse effects including headache, dry mouth, nasopharyngitis, dizziness, nausea, and diarrhea will be recorded |
Countries
Egypt
Contacts
STUDY_DIRECTORNoha Mahmoud ELkhodary, PhD
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
PRINCIPAL_INVESTIGATORAya Emad Fouda, MSc in Clinical Pharmacy
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Outcome results
None listed