Clinical trial NCT02251431: Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome
Official title: MB001-067 A PROSPECTIVE, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, RANDOMIZED TRIAL OF EXTENDED RELEASE EXENATIDE VERSUS PLACEBO (COHORT A) AND A PROSPECTIVE, SINGLE GROUP, OPEN-LABEL, BLINDED OUTCOME TRIAL OF EXTENDED RELEASE EXENATIDE (COHORT B) IN DIABETIC PATIENTS WITH TYPE 4 CARDIORENAL SYNDROME (EXTEND-CRS TRIAL) AMENDMENT 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Chronic Kidney Disease
Left Ventricular Diastolic Dysfunction
Keywords: diabetes mellitus
chronic kidney disease
diastolic function
cardiac fibrosis
cardiac strain
cardiac biomarker
renal biomarker
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2014-09-29
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Galectin-3
timeFrame: 38 weeks
measure: ST2
timeFrame: 38 weeks
measure: NGAL
timeFrame: 38 weeks
measure: KIM-1
timeFrame: 38 weeks
measure: L-FABP
timeFrame: 38 weeks
measure: IL-18
timeFrame: 38 weeks
measure: Alpha GST
timeFrame: 38 weeks
measure: Troponin I
timeFrame: 38 weeks
measure: Pi GST
timeFrame: 38 weeks
measure: NAG
timeFrame: 38 weeks
measure: Cystatin-C
timeFrame: 38 weeks
measure: BNP
timeFrame: 38 weeks
measure: ACR
timeFrame: 38 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital
state: Texas
Study officials:
affiliation: Baylor Research Institute
name: Peter A McCullough, MD, MPH
role: STUDY_CHAIR
References:
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citation: Davidson MH. Cardiovascular effects of glucagonlike peptide-1 agonists. Am J Cardiol. 2011 Aug 2;108(3 Suppl):33B-41B. doi: 10.1016/j.amjcard.2011.03.046.
citation: Levine GD, Rosai J, Bearman RM, Polliack A. The fine structure of thymoma, with emphasis on its differential diagnosis. A study of ten cases. Am J Pathol. 1975 Oct;81(1):49-86.
citation: Best JH, Hoogwerf BJ, Herman WH, Pelletier EM, Smith DB, Wenten M, Hussein MA. Risk of cardiovascular disease events in patients with type 2 diabetes prescribed the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide twice daily or other glucose-lowering therapies: a retrospective analysis of the LifeLink database. Diabetes Care. 2011 Jan;34(1):90-5. doi: 10.2337/dc10-1393. Epub 2010 Oct 7.
citation: McCullough PA, Olobatoke A, Vanhecke TE. Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med. 2011;12(4):200-10. doi: 10.3909/ricm0624.
citation: Wang YC, Yu CC, Chiu FC, Tsai CT, Lai LP, Hwang JJ, Lin JL. Soluble ST2 as a biomarker for detecting stable heart failure with a normal ejection fraction in hypertensive patients. J Card Fail. 2013 Mar;19(3):163-8. doi: 10.1016/j.cardfail.2013.01.010.
citation: Jellis C, Martin J, Narula J, Marwick TH. Assessment of nonischemic myocardial fibrosis. J Am Coll Cardiol. 2010 Jul 6;56(2):89-97. doi: 10.1016/j.jacc.2010.02.047.