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

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ClinicalTrials.gov Identifier: NCT03029351
Recruitment Status : Not yet recruiting
First Posted : January 24, 2017
Last Update Posted : January 25, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Paresh Dandona, University at Buffalo

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.

Condition or disease Intervention/treatment Phase
Type2 Diabetes Kidney Diseases Drug: Exenatide Extended Release for Inj Susp 2 MG Drug: Placebos Phase 4

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  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
Estimated Study Start Date : February 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

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 Name: 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: Placebos
placebo treatment weekly for 1 year in type 2 diabetes with micro-and macroalbuminuria




Primary Outcome Measures :
  1. change from baseline in albuminuria levels [ Time Frame: 13, 26, 39, 56 weeks ]
    change from baseline in albuminuria level at weeks 12, 26, 39 and 56 following Exenatide extended release and placebo treatments


Secondary Outcome Measures :
  1. change in albuminuria category (micro or macro) [ Time Frame: 13, 26, 39, 56 weeks ]
  2. change in creatinine clearance [ Time Frame: 13, 26, 39, 56 weeks ]
  3. change in Cystatin C [ Time Frame: 13, 26, 39, 56 weeks ]
  4. change in TGFβ [ Time Frame: 1, 26, 39, 56 weeks ]
  5. change in type I and IV collagen [ Time Frame: 12, 26, 39, 56 weeks ]
  6. Change in CTGF [ Time Frame: 13, 26, 39, 56 weeks ]
  7. change in fibronectin levels [ Time Frame: 13, 26, 39, 56 weeks ]
  8. change in the expression of SMAD3 [ Time Frame: 13, 26, 39, 56 weeks ]
  9. change in SMAD4 [ Time Frame: 13, 26, 39, 56 weeks ]
  10. change in NQO-1 [ Time Frame: 13, 26, 39, 56 weeks ]
  11. change in GST-1P [ Time Frame: 13, 26, 39, 56 weeks ]
  12. change in HO-1 [ Time Frame: 13, 26, 39, 56 weeks ]
  13. Change in Nrf-2/keap-1 [ Time Frame: 13, 26, 39, 56 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03029351


Contacts
Contact: Paresh Dandona, MD 716-898-1950 pdandona@kaleidahealth.org
Contact: Husam Ghanim, PhD 716-881-8924 ghanim@buffalo.edu

Sponsors and Collaborators
University at Buffalo
AstraZeneca

Responsible Party: Paresh Dandona, SUNY Distinguished Professor, University at Buffalo
ClinicalTrials.gov Identifier: NCT03029351     History of Changes
Other Study ID Numbers: 1981 GLP
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: January 25, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Paresh Dandona, University at Buffalo:
albuminuria
GLP-1 Receptor Agonist
Type 2 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Kidney Diseases
Albuminuria
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Proteinuria
Urination Disorders
Urological Manifestations
Signs and Symptoms
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists