GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes (1981)

This is a prospective study to evaluate effect of Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Kidney Diseases; Type2 Diabetes
• Intervention / Treatment: Drug: Exenatide Extended Release for Inj Susp 2 MG; Drug: Placebo

Detailed Description

This is a prospective study to evaluate effect of Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo. The similarities in baseline values between the study groups will be compared using appropriate parametric tests. Transformations of the data on order to meet statistical assumptions may be considered. All statistical analysis will be carried out using SPSS software (SPSS Inc, Chicago, Illinois) based on intention to treat principle. Data will be presented as mean±standard error. The primary endpoint of the study is the change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments. Fasting samples collected at weeks 0, 12, 26, 39 and 56 will be used for this assessment with values at week 0 considered as baseline. Changes from baselines form both drugs arms will be compared to those from the placebo arms in both the micro and macroalbuminuria groups. The statistical analysis will be done using mixed model for repeated measurement (MMRM) analysis with assigned α value of 0.05. Our preliminary data on retrospective analysis of the difference in albuminuria following GLP-1RA treatment for 2.5 yrs in T2DM patients with micro and macroalbuminuria show regression of albuminuria (UACR) by approximately 55mg/mg and 500mg/g (about 50% reduction), respectively. Conservatively estimating a difference in the change from baseline in albuminuria after 1 year between the Exenatide extended release and placebo groups (across both albuminuria groups) of 60mg/g, with standard deviation of no more than 91mg/g, a sample size of 38 patients per group should provide adequate power (beta = 0.2) to detect a significant difference (alpha = 0.05). Assuming a drop-out rate of 15% and 2:1 drug:placebo randomization ratio, 60 active and 30 control will be recruited for a total of 90 patients (rounded up). Patients will be enrolled based on a predetermined stratification according to the two albuminuria categories (micro and macro at 1:1 ratio) with 45 patients in each.

The secondary end points include the comparison of the changes in albuminuria based on baseline albuminuria category (micro or macro), creatinine clearance, Cystatin C, TGFβ, type I and IV collagen, CTGF, and fibronectin levels, the expression of SMAD3, SMAD4, NQO-1, GST-1P and HO-1, Nrf-2/keap-1 system activation between the Exenatide extended release and placebo groups and across albuminuria categories

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Williamsville, New York, United States, 14221
      • Diabetes Endocrinology Research Center of WNY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type 2 Diabetes for at least 1 year.
• Microalbuminuria for at least 6 months (UACR: 30-300 mg/g)
• Macroalbuminuria for at least 6 months (UACR: >300 mg/g)
• HbA1c of ≤10%
• Ages 18-65 years (inclusive of ages 18 and 65)
• On ARBs/ACEi for at >3months

Exclusion Criteria:

• Use of GLP-1 Receptor agonists or SGLT-2 inhibitors therapy in the last 3 months
• History or risk for pancreatitis (e.g., history of gallstones, alcohol abuse, and hypertriglyceridemia)
• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous 3 months

• Hepatic disease: Severe hepatic insufficiency and/or significant abnormal liver function defined as:

  1. Aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
  2. Total bilirubin >2.0 mg/dL (34.2 µmol/L)
  3. Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
  4. Liver function tests more than 3 times the upper limit of normal
• Renal impairment (serum eGFR <30 ml/min)
• HIV
• Inability to give informed consent
• History of gastroparesis
• History of medullary thyroid carcinoma or MEN 2 syndrome
• Alcoholism
• Hypertriglyceridemia (>500 mg/dl).
• Any other life-threatening, non-cardiac disease
• Uncontrolled hypertension (BP > 160/100 mm of Hg)
• Congestive Heart Failure class III or IV
• Use of an investigational agent or therapeutic regimen within 30 days of study
• Participation in any other concurrent clinical trial
• Pregnant or breastfeeding patients or females of childbearing age not on 2 forms of acceptable contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide extended release; Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.	Drug: Exenatide Extended Release for Inj Susp 2 MG; Exenatide extended release treatment weekly for 1 year in T2DM patients with micro- and macroalbuminuria; Other Names: Bydureon
Placebo Comparator: Placebo; Placebo treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to Exenatide extended release.	Drug: Placebo; placebo treatment weekly for 1 year in type 2 diabetes with micro-and macroalbuminuria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Urinary Albuminuria Levels	change from baseline in 24-hr urinary albuminuria (albumin/creatine) level at week 52 following Exenatide extended release OR placebo treatments	baseline and 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in albuminuria category (micro or macro)	change in albuminuria category between normal to micro to macro albuminuria at12, 26, 39, 56 weeks	12, 26, 39, 56 weeks
change in creatinine clearance	change from baseline in creatinine at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in Cystatin C	change from baseline in cystatin C at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in TGFβ	change from baseline in TGFβ level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in type I and IV collagen	change from baseline in Type I and IV collagen levels at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
Change in CTGF	change from baseline in CTGF level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in fibronectin levels	change from baseline in fibronectin level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in the expression of SMAD3	change from baseline in SMAD3 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in SMAD4	change from baseline in SMAD4 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12 26, 39, 56 weeks
change in NQO-1	change from baseline in NQO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in GST-1P	change from baseline in GST-1P level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
change in HO-1	change from baseline in HO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks
Change in Nrf-2/keap-1	change from baseline in Nrf-2/keap-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments	12, 26, 39, 56 weeks

Collaborators and Investigators

• Sponsor: University at Buffalo
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2017
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: January 20, 2017
• First Submitted That Met QC Criteria: January 20, 2017
• First Posted (Estimated): January 24, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; albuminuria; GLP-1 Receptor Agonist
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Albuminuria; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Glucagon-Like Peptide-1 Receptor Agonists; Exenatide
• Other Study ID Numbers: 1981 GLP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes