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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02251431
• Other study ID #: 014-149
• Secondary ID: D5551L00004/ISSE
• Status: Completed
• Phase: Phase 3
• Start date: November 2015
• Est. completion date: December 2019

Study information

• Verified date: June 2020
• Source: Baylor Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardio-Renal Syndrome
• Chronic Kidney Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Diseases
• Left Ventricular Diastolic Dysfunction
• Renal Insufficiency, Chronic
• Type 2 Diabetes Mellitus
• Ventricular Dysfunction, Left

Intervention

Drug:
• BYDUREON
Exenatide-extended release, Cohorts A and B
• Placebo
Cohort A only

Locations

Country	Name	City	State
United States	Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

Chinnaiyan KM, Alexander D, Maddens M, McCullough PA. Curriculum in cardiology: integrated diagnosis and management of diastolic heart failure. Am Heart J. 2007 Feb;153(2):189-200. doi: 10.1016/j.ahj.2006.10.022. — View 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. — View 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. — View 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. — View 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. Erratum In: Rev Cardiovasc Med. 2012;13(1):e52. — View 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. — View Citation

Outcome

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