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

NCT02251431 | Completed Phase 3 Results DMC

• 2 other identifiers: 014-149D5551L00004/ISSEXEN0013
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease; Left Ventricular Diastolic Dysfunction; Type 2 Diabetes Mellitus

Keywords

diabetes mellitus; chronic kidney disease; diastolic function; cardiac fibrosis; cardiac strain; cardiac biomarker; renal biomarker

Outcome Measures

Primary Outcomes (13)

• Galectin-3

  Mean change in plasma galectin-3 (pg/ml)

  38 weeks

• ST2

  Mean change in plasma ST2 (pg/ml)

  38 weeks

• NGAL

  Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio

  38 weeks

• KIM-1

  Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio

  38 weeks

• L-FABP

  Mean change in urine L-type fatty acid binding protein:Cr ratio

  38 weeks

• IL-18

  Mean change in urine interleukin-18:Cr ratio

  38 weeks

• Alpha GST

  Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio

  38 weeks

• Troponin I

  Mean change in plasma ultrasensitive troponin I (pg/ml)

  38 weeks

• Pi GST

  Mean change in pi glutathione S-transferase (piGST):Cr ratio

  38 weeks

• NAG

  Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio

  38 weeks

• Cystatin-C

  Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)

  38 weeks

• BNP

  Mean change in plasma B-type natriuretic peptide BNP (pg/ml)

  38 weeks

• ACR

  Mean change in urine albumin:Cr ratio (ACR)

  38 weeks

Study Arms (2)

Exenatide-extended release

EXPERIMENTAL

Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks

Drug: BYDUREON

Placebo

PLACEBO COMPARATOR

Matching placebo subcutaneously once per week x 38 weeks

Drug: Placebo

Interventions

BYDUREON DRUG

Exenatide-extended release, Cohorts A and B

Exenatide-extended release

Placebo DRUG

Cohort A only

Also known as: Matching placebo subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor Research Institute: lead

Study Sites (1)

Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital

Dallas, Texas, 75226, United States

Location

Related Publications (7)

• 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.

  PMID: 17239676 BACKGROUND

• 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.

  PMID: 21802579 BACKGROUND

• 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.

  PMID: 1080957 BACKGROUND

• 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.

  PMID: 20929995 BACKGROUND

• 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.

  PMID: 22249510 BACKGROUND

• 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.

  PMID: 23482076 BACKGROUND

• 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.

  PMID: 20620723 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Ventricular Dysfunction, Left; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Limitations and Caveats

Our recruitment stopped early due to low accrual rate. Hence, null findings may be a result of lack of statistical power. Accordingly, our results should be interpreted as hypothesis-generating.

Results Point of Contact

• Title: Biostatistician
• Organization: Baylor Scott & White Research Institute

gelareh.rahimighazikalayeh@bswhealth.org

8033190755

Study Officials

• Peter A McCullough, MD, MPH

  Baylor Research Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: September 29, 2014
• Study Start: November 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 19, 2026
• Results First Posted: May 17, 2023

Record last verified: 2020-06

Locations

US (1)