Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy

NCT02690883 | Completed Phase 4 DMC

• 1 other identifier: ESR-14-10425
• Study Type: interventional
• Target: 92
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Diabetic Nephropathies

Outcome Measures

Primary Outcomes (1)

• 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

  from baseline at Week 24

Secondary Outcomes (6)

• the percentage change of ACR

  from baseline at Week 24

• Change in 24h-UAER

  from baseline at Week 24

• Change in HbA1c

  from baseline at Week 24

• Change in FPG

  from baseline at Week 24

• Change in Weight

  from baseline at Week 24

Study Arms (2)

Lispro

ACTIVE COMPARATOR

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.

Drug: Lispro

Exenatide

EXPERIMENTAL

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.

Drug: Exenatide

Interventions

Exenatide DRUG

Exenatide (Astrazeneca ) 5 μg(initial dose)/10ug(maintenance dose) Subcutaneous injection Bid

Also known as: Byetta

Exenatide

Lispro DRUG

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.

Also known as: Humalog

Lispro

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• h 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).
• eGFR \>30ml/min(the result is valid for seven days).

You may not qualify if:

• ．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.
• \. 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.
• \. Previous treatment with any Thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 3 months.
• \. History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to exenatide.
• \. Blood amylase and/or lipase \> 2 times the upper limit of the normal (ULN) laboratory range.
• \. Hyperkalemia (K+\>5.5mmol/L).
• \. eGFR \<30ml/min/1.73m2.
• \. Patients without diabetic retinopathy.
• \. Triglycerides (fasting) \> 4.5 mmol/L (400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).
• \. 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.
• \. 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.
• \. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.
• \. History of chronic pancreatitis or idiopathic acute pancreatitis.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Related Publications (17)

• KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154. doi: 10.1053/j.ajkd.2006.12.005. No abstract available.

  PMID: 17276798 BACKGROUND

• Lim AKh. Diabetic nephropathy - complications and treatment. Int J Nephrol Renovasc Dis. 2014 Oct 15;7:361-81. doi: 10.2147/IJNRD.S40172. eCollection 2014.

  PMID: 25342915 BACKGROUND

• de Zeeuw D, Parving HH, Henning RH. Microalbuminuria as an early marker for cardiovascular disease. J Am Soc Nephrol. 2006 Aug;17(8):2100-5. doi: 10.1681/ASN.2006050517. Epub 2006 Jul 6.

  PMID: 16825327 BACKGROUND

• Filippatos TD, Elisaf MS. Effects of glucagon-like peptide-1 receptor agonists on renal function. World J Diabetes. 2013 Oct 15;4(5):190-201. doi: 10.4239/wjd.v4.i5.190.

  PMID: 24147203 BACKGROUND

• Lu B, Song X, Dong X, Yang Y, Zhang Z, Wen J, Li Y, Zhou L, Zhao N, Zhu X, Hu R. High prevalence of chronic kidney disease in population-based patients diagnosed with type 2 diabetes in downtown Shanghai. J Diabetes Complications. 2008 Mar-Apr;22(2):96-103. doi: 10.1016/j.jdiacomp.2007.08.001.

  PMID: 18280439 BACKGROUND

• Lai X, Zhang AH, Chen SY, He L, Su CY, Fan MH, Wang T. Outcomes of stage 1-5 chronic kidney disease in Mainland China. Ren Fail. 2014 May;36(4):520-5. doi: 10.3109/0886022X.2013.875859. Epub 2014 Jan 23.

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• Diabetes Control and Complications Trial Research Group; Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86. doi: 10.1056/NEJM199309303291401.

  PMID: 8366922 BACKGROUND

• Tomino Y. Pathogenesis and treatment of chronic kidney disease: a review of our recent basic and clinical data. Kidney Blood Press Res. 2014;39(5):450-89. doi: 10.1159/000368458. Epub 2014 Nov 30.

  PMID: 25501571 BACKGROUND

• Kobori H, Mori H, Masaki T, Nishiyama A. Angiotensin II blockade and renal protection. Curr Pharm Des. 2013;19(17):3033-42. doi: 10.2174/1381612811319170009.

  PMID: 23176216 BACKGROUND

• Park CW, Kim HW, Ko SH, Lim JH, Ryu GR, Chung HW, Han SW, Shin SJ, Bang BK, Breyer MD, Chang YS. Long-term treatment of glucagon-like peptide-1 analog exendin-4 ameliorates diabetic nephropathy through improving metabolic anomalies in db/db mice. J Am Soc Nephrol. 2007 Apr;18(4):1227-38. doi: 10.1681/ASN.2006070778. Epub 2007 Mar 14.

  PMID: 17360951 BACKGROUND

• Xu WW, Guan MP, Zheng ZJ, Gao F, Zeng YM, Qin Y, Xue YM. Exendin-4 alleviates high glucose-induced rat mesangial cell dysfunction through the AMPK pathway. Cell Physiol Biochem. 2014;33(2):423-32. doi: 10.1159/000358623. Epub 2014 Feb 11.

  PMID: 24556697 BACKGROUND

• Zhang H, Zhang X, Hu C, Lu W. Exenatide reduces urinary transforming growth factor-beta1 and type IV collagen excretion in patients with type 2 diabetes and microalbuminuria. Kidney Blood Press Res. 2012;35(6):483-8. doi: 10.1159/000337929. Epub 2012 Jun 8.

  PMID: 22687869 BACKGROUND

• Imamura S, Hirai K, Hirai A. The glucagon-like peptide-1 receptor agonist, liraglutide, attenuates the progression of overt diabetic nephropathy in type 2 diabetic patients. Tohoku J Exp Med. 2013 Sep;231(1):57-61. doi: 10.1620/tjem.231.57.

  PMID: 24064677 BACKGROUND

• Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med. 2008 May 1;358(18):1970-1; discussion 1971-2. No abstract available.

  PMID: 18456920 BACKGROUND

• Bloomgren G, Braum D, Kolterman O. Exenatide and rare adverse events. N Engl J med 2008; 358: 1971-2.

  BACKGROUND

• Yanagisawa K, Ashihara J, Obara S, Wada N, Takeuchi M, Nishino Y, Maeda S, Ishibashi Y, Yamagishi S. Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients. Diabetes Metab Res Rev. 2014 Nov;30(8):693-700. doi: 10.1002/dmrr.2537.

  PMID: 24639403 BACKGROUND

• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.

  PMID: 39963952 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies

Interventions

Exenatide; Insulin Lispro

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Xue, PhD

  Department of Endocrinology & Metabolism, Nanfang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Endocrinology and Metabolism

Study Record Dates

• First Submitted: February 20, 2016
• First Posted: February 24, 2016
• Study Start: April 8, 2016
• Primary Completion: December 13, 2019
• Study Completion: December 30, 2019
• Last Updated: March 9, 2020

Record last verified: 2020-03