Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus
Chronic Kidney Disease
Left Ventricular Diastolic Dysfunction

Interventions: Drug: BYDUREON
Drug: Placebo

Registration Number: NCT02251431

Lead Sponsor: Baylor Research Institute

Brief 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.

Detailed Description: Primary Aim

Among adult individuals with type 2 diabetes mellitus (T2DM) and at risk for diastolic heart failure (DHF) and mildly reduced renal filtration function (Type 4 cardiorenal syndrome), to evaluate the quantitative impact on the MISS (myocardial injury summary score) cardiac biomarker score, cardiac fibrosis by MRI, cardiac strain by ultrasonography and strain rate imaging, and KISS (kidney injury summary score) kidney biomarker score after 38 weeks of treatment with exenatide extended-release or placebo.

Secondary Aim

To evaluate the inter-relationships between demographic, clinical, and biochemical variables (MISS score, KISS score) and of progressive cardiac fibrosis as assessed by MRI, strain-rate imaging, and in adult individuals with T2DM and at risk for DHF (Type 4 cardiorenal syndrome).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 57

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide-extended release	BYDUREON	Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks
Placebo	Placebo	Matching placebo subcutaneously once per week x 38 weeks

Primary Outcome Measures

Name	Time	Method
KIM-1	38 weeks	Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio
Galectin-3	38 weeks	Mean change in plasma galectin-3 (pg/ml)
ST2	38 weeks	Mean change in plasma ST2 (pg/ml)
L-FABP	38 weeks	Mean change in urine L-type fatty acid binding protein:Cr ratio
NGAL	38 weeks	Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio
NAG	38 weeks	Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio
Cystatin-C	38 weeks	Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)
IL-18	38 weeks	Mean change in urine interleukin-18:Cr ratio
Troponin I	38 weeks	Mean change in plasma ultrasensitive troponin I (pg/ml)
Pi GST	38 weeks	Mean change in pi glutathione S-transferase (piGST):Cr ratio
BNP	38 weeks	Mean change in plasma B-type natriuretic peptide BNP (pg/ml)
ACR	38 weeks	Mean change in urine albumin:Cr ratio (ACR)
Alpha GST	38 weeks	Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio