Back to resultsEffect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy
Primary Purpose
Diabetic Nephropathies
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Exenatide
Lispro
Sponsored by
About this trial
This is an interventional prevention trial for Diabetic Nephropathies
Eligibility Criteria
Inclusion Criteria:
- Provision of informed consent prior to any study specific procedures.
- Diagnosed with type 2 diabetes with HbA1c ≥ 7.0% and ≤ 11.0% at screening (the result is valid for seven days).
- Men and women (non-pregnant and using a medically approved birth-control method) aged from 18 to 80 at screening.
- Body mass index (BMI) ≥18 and ≤35 kg/m2.
- Blood Pressure (BP) ≥ 90/60mmHg and ≤160/100mmHg.
6.24h urinary albumin excretion rate (UAE) >0.3g/24h after 3 months treatment with several hypoglycemic agents (sulphonylureas, metformin, AG-inhibitor, meglitinides or insulin), ACEI/ARB and salt restriction(the result is valid for seven days).
7.eGFR >30ml/min(the result is valid for seven days).
Exclusion Criteria:
1．Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
2. Diagnosis or history of:
- Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.
Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
3. Previous treatment with any Thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 3 months.
4. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to exenatide.
5. Blood amylase and/or lipase > 2 times the upper limit of the normal (ULN) laboratory range.
6. Hyperkalemia (K+>5.5mmol/L).
7. eGFR <30ml/min/1.73m2.
8. Patients without diabetic retinopathy.
9. Triglycerides (fasting) > 4.5 mmol/L (400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).
10. Patients with clinically apparent liver disease characterized by ALT or AST > 3ULN confirmed on two consecutive measurements (by local laboratory) within 4 weeks prior to screening period.
11. Significant cardiovascular history within the past 3 months prior to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
12. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.
13. History of chronic pancreatitis or idiopathic acute pancreatitis.
14. History of medullary thyroid carcinoma.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Lispro
Exenatide
Arm Description
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
Outcomes
Primary Outcome Measures
the percentage change of 24h-UAER(urinary albumin excretion rates) from baseline at Week 24
the percentage change of 24h-UAER=(24h-UAERweek24 - 24h-UAERbaseline)/ 24h-UAERbaseline
Secondary Outcome Measures
the percentage change of ACR
the percentage change of ACR=(ACRweek24 - ACRbaseline)/ ACRbaseline
Change in 24h-UAER
Change in 24h-UAER =24h-UAERweek24 - 24h-UAERbaseline
Change in HbA1c
Change in HbA1c=HbA1cweek24-HbA1cbaseline
Change in FPG
Change in FPG=FPGweek24-FPGbaseline
Change in Weight
Change in weight=Weightweek24-Weightbaseline
Change in Blood pressure
Change in blood pressure=SBPweek24-SBPbaseline
Full Information
NCT ID
NCT02690883
First Posted
February 20, 2016
Last Updated
March 5, 2020
Sponsor
Nanfang Hospital, Southern Medical University
1. Study Identification
Unique Protocol Identification Number
NCT02690883
Brief Title
Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy
Official Title
Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy: a 24- Week Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
April 8, 2016 (Actual)
Primary Completion Date
December 13, 2019 (Actual)
Study Completion Date
December 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nanfang Hospital, Southern Medical University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multi-center, randomized, parallel study to evaluate effect of exenatide on 24h-UAER in patients with diabetic nephropathy.
Screening will be made to select eligible participants before intervention. The trial will include 2-week run-in period of stable doses of glargine plus lispro insulin and 24-week treatment period. After the run-in period, patients were randomly assigned to one of two groups for antihyperglycaemic therapies for a total of 24-weeks: glargine plus exenatide and continued glargine plus lispro insulin. The treatment of exenatide will be initiated by 5ug bid, and uptitrated to 10 ug bid after 4 weeks and then maintained at 10ug bid until the completion of the study. Lispro insulin will be initially treated according to the insulin dosage of previous antihyperglycaemic therapies, and further titrated up at 4-week intervals until to reach the target fasting blood glucose (FPG).
Detailed Description
Objective:
To evaluate effect of exenatide on 24-UAER in patients with diabetic nephropathy
Hypothesis:
Compared with glargine plus lispro group, at 24 weeks, glargine plus exenatide group can: 1) take more significant reduction of 24h-UAER; 2) take more reduction of ACR; 3) take more weight loss, blood pressure reduction; 4) take lower hypoglycemia incidence and less insulin dosage.
Primary endpoint： The proportion of reduction of 24h-UAER(urinary albumin excretion rates)
Secondary endpoints： 24h-UAER at 24 weeks; the rate of urinary albumin to creatinine ratio(ACR) change at 24 weeks; HbA1c, FPG,PPG, weight , BP
Treatment duration： 24weeks
Patient/Sites： 90 patients / 3 sites
Timeline (best case)： Planed duration of recruitment period: 6 month Planed date for first screening: 1 October 2015 Planed completion of the last subject: 1 March 2017 Planned completion of clinical trial report: 30 October 2017
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Nephropathies
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lispro
Arm Type
Active Comparator
Arm Description
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
Arm Title
Exenatide
Arm Type
Experimental
Arm Description
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta
Intervention Description
Exenatide (Astrazeneca ) 5 μg(initial dose)/10ug(maintenance dose) Subcutaneous injection Bid
Intervention Type
Drug
Intervention Name(s)
Lispro
Other Intervention Name(s)
Humalog
Intervention Description
Lispro (Eli Lilly), the dosage is initiated according to the previous treatment plan and weight of the patients, distribute the dosage to 1:1:1 before 3 meals, titration following PPG <10.0mmol/L.
Primary Outcome Measure Information:
Title
the percentage change of 24h-UAER(urinary albumin excretion rates) from baseline at Week 24
Description
the percentage change of 24h-UAER=(24h-UAERweek24 - 24h-UAERbaseline)/ 24h-UAERbaseline
Time Frame
from baseline at Week 24
Secondary Outcome Measure Information:
Title
the percentage change of ACR
Description
the percentage change of ACR=(ACRweek24 - ACRbaseline)/ ACRbaseline
Time Frame
from baseline at Week 24
Title
Change in 24h-UAER
Description
Change in 24h-UAER =24h-UAERweek24 - 24h-UAERbaseline
Time Frame
from baseline at Week 24
Title
Change in HbA1c
Description
Change in HbA1c=HbA1cweek24-HbA1cbaseline
Time Frame
from baseline at Week 24
Title
Change in FPG
Description
Change in FPG=FPGweek24-FPGbaseline
Time Frame
from baseline at Week 24
Title
Change in Weight
Description
Change in weight=Weightweek24-Weightbaseline
Time Frame
from baseline at Week 24
Title
Change in Blood pressure
Description
Change in blood pressure=SBPweek24-SBPbaseline
Time Frame
from baseline at Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Provision of informed consent prior to any study specific procedures.
Diagnosed with type 2 diabetes with HbA1c ≥ 7.0% and ≤ 11.0% at screening (the result is valid for seven days).
Men and women (non-pregnant and using a medically approved birth-control method) aged from 18 to 80 at screening.
Body mass index (BMI) ≥18 and ≤35 kg/m2.
Blood Pressure (BP) ≥ 90/60mmHg and ≤160/100mmHg.
6.24h urinary albumin excretion rate (UAE) >0.3g/24h after 3 months treatment with several hypoglycemic agents (sulphonylureas, metformin, AG-inhibitor, meglitinides or insulin), ACEI/ARB and salt restriction(the result is valid for seven days).
7.eGFR >30ml/min(the result is valid for seven days).
Exclusion Criteria:
1．Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
2. Diagnosis or history of:
Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.
Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
3. Previous treatment with any Thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 3 months.
4. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to exenatide.
5. Blood amylase and/or lipase > 2 times the upper limit of the normal (ULN) laboratory range.
6. Hyperkalemia (K+>5.5mmol/L).
7. eGFR <30ml/min/1.73m2.
8. Patients without diabetic retinopathy.
9. Triglycerides (fasting) > 4.5 mmol/L (400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).
10. Patients with clinically apparent liver disease characterized by ALT or AST > 3ULN confirmed on two consecutive measurements (by local laboratory) within 4 weeks prior to screening period.
11. Significant cardiovascular history within the past 3 months prior to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
12. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.
13. History of chronic pancreatitis or idiopathic acute pancreatitis.
14. History of medullary thyroid carcinoma.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xue, PhD
Organizational Affiliation
Department of Endocrinology & Metabolism, Nanfang Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy
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