Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome
Condition: Type 2 Diabetes Mellitus; Chronic Kidney Disease; Left Ventricular Diastolic Dysfunction
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Cardio-Renal Syndrome; Ventricular Dysfunction, Left; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: BYDUREON; Placebo
Intervention description: Exenatide-extended release, Cohorts A and B; Cohort A only
Intervention MeSH terms: Exenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetes mellitus; chronic kidney disease; diastolic function; cardiac fibrosis; cardiac strain; cardiac biomarker; renal biomarker

Summary:

      Among adult individuals with type 2 diabetes mellitus and at risk for heart failure with
      impaired relaxation of the heart mildly reduced kidney filtration function (Type 4
      cardiorenal syndrome) this trial will evaluate the quantitative impact of 38 weeks of
      treatment with exenatide extended-release injections versus placebo. on a cardiac biomarker
      blood test score, cardiac fibrosis seen on magnetic resonance scanning, cardiac strain
      identified by ultrasonography and strain rate imaging, and a kidney urine biomarker score.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18

          -  Type 2 diabetes mellitus with hemoglobin A1C 6.6-9.9% with or without the use of
             insulin

          -  Estimated glomerular filtration rate (eGFR) between 50 and 90 ml/min/1.73 m2

        Exclusion Criteria:

          -  Allergy or intolerance to gadolinium

          -  Implanted cardiac pacemaker, defibrillator, loop recorder, or other implanted metallic
             device

          -  Any other metallic implanted device that is a contra-indication to MRI scanning

          -  eGFR < 50 ml/min/1.73 m2

          -  eGFR > 90 ml/min/1.73 m2

          -  Patient has ever been treated with an approved or investigational GLP-1 receptor
             agonist e.g. BYETTA™ (exenatide), BYDUREON™ (Exenatide extended-release), VICTOZA™
             (liraglutide), or taspoglutide

          -  Patient is enrolled in another experimental protocol which involves the use of an
             investigational drug or device, or an intervention that would interfere with the
             conduct of the trial.

          -  Disorders of iron metabolism

          -  Collagen vascular diseases

          -  Myocardial infarction

          -  Use of DDP4 inhibitors, and PPAR gamma agonists

          -  Pregnancy or planned pregnancy during the trial period

          -  Hemoglobin A1C of ≥ 10.0% or <6.6%

          -  Fasting glucose ≥ 260 mg/dl

          -  Clinically significant abnormal baseline laboratories

          -  Morbid obesity or body girth that prohibits the ability to undergo echocardiography or
             MRI scanning with high-quality image results

          -  Renal transplantation

          -  Severe gastrointestinal, liver, or neurodegenerative disease

          -  Decompensated liver cirrhosis (Child-Pugh score >7)

          -  New York Heart Association Class III or IV heart failure

          -  Patients have alanine aminotransaminase (ALT) greater than 5 times the upper limit of
             the reference range.

          -  Prior pancreatitis

          -  Personal or family history of medullary thyroid adenoma or carcinoma (MTC)

          -  Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

          -  History of severe hypoglycemia

          -  Prior bariatric surgery