GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes (1981)
Primary Purpose
Type2 Diabetes, Kidney Diseases
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Exenatide Extended Release for Inj Susp 2 MG
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type2 Diabetes focused on measuring albuminuria, GLP-1 Receptor Agonist, Type 2 Diabetes
Eligibility Criteria
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:
- Aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
- Total bilirubin >2.0 mg/dL (34.2 µmol/L)
- Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
- 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.
Sites / Locations
- Diabetes Endocrinology Research Center of WNY
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Exenatide extended release
Placebo
Arm Description
Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.
Placebo treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to Exenatide extended release.
Outcomes
Primary Outcome Measures
change from baseline in albuminuria levels
change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Secondary Outcome Measures
change in albuminuria category (micro or macro)
change in albuminuria category between normal to micro to macro albuminuria at12, 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
change in Cystatin C
change from baseline in cystatin C at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
change in TGFβ
change from baseline in TGFβ level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
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
Change in CTGF
change from baseline in CTGF level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
change in fibronectin levels
change from baseline in fibronectin level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
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
change in SMAD4
change from baseline in SMAD4 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
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
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
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
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
Full Information
NCT ID
NCT03029351
First Posted
January 20, 2017
Last Updated
January 23, 2023
Sponsor
University at Buffalo
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT03029351
Brief Title
GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
Acronym
1981
Official Title
GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
termination by sponsor
Study Start Date
January 10, 2017 (Actual)
Primary Completion Date
July 2019 (Actual)
Study Completion Date
July 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University at Buffalo
Collaborators
AstraZeneca
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes, Kidney Diseases
Keywords
albuminuria, GLP-1 Receptor Agonist, Type 2 Diabetes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Exenatide extended release
Arm Type
Experimental
Arm Description
Exenatide extended release treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to placebo.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo treatment for 1 year on albuminuria levels in T2DM patients with micro- and macroalbuminuria compared to Exenatide extended release.
Intervention Type
Drug
Intervention Name(s)
Exenatide Extended Release for Inj Susp 2 MG
Other Intervention Name(s)
Bydureon
Intervention Description
Exenatide extended release treatment weekly for 1 year in T2DM patients with micro- and macroalbuminuria
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo treatment weekly for 1 year in type 2 diabetes with micro-and macroalbuminuria
Primary Outcome Measure Information:
Title
change from baseline in albuminuria levels
Description
change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Secondary Outcome Measure Information:
Title
change in albuminuria category (micro or macro)
Description
change in albuminuria category between normal to micro to macro albuminuria at12, 26, 39, 56 weeks
Time Frame
12, 26, 39, 56 weeks
Title
change in creatinine clearance
Description
change from baseline in creatinine at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in Cystatin C
Description
change from baseline in cystatin C at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in TGFβ
Description
change from baseline in TGFβ level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in type I and IV collagen
Description
change from baseline in Type I and IV collagen levels at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
Change in CTGF
Description
change from baseline in CTGF level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in fibronectin levels
Description
change from baseline in fibronectin level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in the expression of SMAD3
Description
change from baseline in SMAD3 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in SMAD4
Description
change from baseline in SMAD4 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12 26, 39, 56 weeks
Title
change in NQO-1
Description
change from baseline in NQO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in GST-1P
Description
change from baseline in GST-1P level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
change in HO-1
Description
change from baseline in HO-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
Title
Change in Nrf-2/keap-1
Description
change from baseline in Nrf-2/keap-1 level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments
Time Frame
12, 26, 39, 56 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
Total bilirubin >2.0 mg/dL (34.2 µmol/L)
Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody IGM, Hepatitis B surface antigen and Hepatitis C virus antibody
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.
Facility Information:
Facility Name
Diabetes Endocrinology Research Center of WNY
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
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