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

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ClinicalTrials.gov Identifier: NCT02251431
Recruitment Status : Recruiting
First Posted : September 29, 2014
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Chronic Kidney Disease Left Ventricular Diastolic Dysfunction Drug: BYDUREON Drug: Placebo Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PROSPECTIVE, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP, RANDOMIZED TRIAL OF EXTENDED RELEASE EXENATIDE VERSUS PLACEBO IN DIABETIC PATIENTS WITH TYPE 4 CARDIORENAL SYNDROME (EXTEND-CRS Trial)
Study Start Date : September 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Experimental: Exenatide-extended release
Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks
Drug: BYDUREON
Exenatide-extended release

Placebo Comparator: Placebo
Matching placebo subcutaneously once per week x 38 weeks
Drug: Placebo
Other Name: Matching placebo subcutaneous injection




Primary Outcome Measures :
  1. Myocardial injury summary score (MISS) [ Time Frame: 38 weeks ]

    This is a mathematical integration of the percent change in Ultrasensitive troponin, B-type natriuretic peptide (BNP), Galectin-3, and ST2 by using the following formula (range -1 to +1)

    MISS(j) = SUM log10 [ Biomarker(i)Peak / Biomarker(i)Baseline ], i = 1, n


  2. Kidney Injury Summary Score (KISS) [ Time Frame: 38 weeks ]

    This is a mathematical integration of the percent change in Tissue Inhibitor of MetalloProteinases-2 (TIMP-2) x Insulin-like Growth Factor Binding Protein-7 (IGFBP-7), also known as the commercially available NephroCheck® Test, Neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio, Kidney injury molecule-1 (KIM-1):Cr ratio, L-Fatty acid binding protein:Cr ratio, Interleukin-18:Cr ratio, Alpha glutathione S-transferase (αGST):Cr ratio, Pi glutathione S-transferase (piGST):Cr ratio, N-acetyl-β-D-glucosaminidase (NAG):Cr ratio, Cystatin-C:Cr ratio (uCysC:Cr), Albumin:Cr ratio (ACR) by using the following formula (range -1 to +1)

    KISS(j) = SUM log10 [ Biomarker(i)Peak / Biomarker(i)Baseline ], i = 1, n


  3. Cardiac fibrosis [ Time Frame: 38 weeks ]
    Mean paired percent change in left ventricular myocardial fibrosis (% of left ventricular mass) by late gadolinium enhancement on cardiac magnetic resonance imaging

  4. Left ventricular strain [ Time Frame: 38 weeks ]
    Mean paired change in left ventricular longitudinal strain (%) by echocardiographic strain-rate imaging (unitless)


Other Outcome Measures:
  1. Galectin-3 [ Time Frame: 38 weeks ]
    Mean paired change in plasma galectin-3 (ng/ml)

  2. ST2 [ Time Frame: 38 weeks ]
    Mean paired change in plasma ST2 (ng/ml)

  3. NephroCheck [ Time Frame: 38 weeks ]
    Mean paired change in urine NephroCheck (Tissue Inhibitor of MetalloProteinases-2 x Insulin-like Growth Factor Binding Protein-7) unitless

  4. NGAL [ Time Frame: 38 weeks ]
    Mean paired change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio

  5. KIM-1 [ Time Frame: 38 weeks ]
    Mean paired change in urine kidney injury molecule-1 (KIM-1):Cr ratio

  6. L-FABP [ Time Frame: 38 weeks ]
    Mean paired change in urine L-type fatty acid binding protein:Cr ratio

  7. IL-18 [ Time Frame: 38 weeks ]
    Mean paired change in urine interleukin-18:Cr ratio

  8. Alpha GST [ Time Frame: 38 weeks ]
    Mean paired change in urine alpha glutathione S-transferase (αGST):Cr ratio

  9. Pi GST [ Time Frame: 38 weeks ]
    Mean paired change in pi glutathione S-transferase (piGST):Cr ratio

  10. NAG [ Time Frame: 38 weeks ]
    Mean paired change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio

  11. Cystatin-C [ Time Frame: 38 weeks ]
    Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)

  12. ACR [ Time Frame: 38 weeks ]
    Mean paired change in urine albumin:Cr ratio (ACR)

  13. LVMI [ Time Frame: 38 weeks ]
    Mean paired change in ventricular mass index (LVMI) (g/m2) by cMRI

  14. Radial Strain [ Time Frame: 38 weeks ]
    Mean paired change in radial strain by strain rate echocardiography (unitless)

  15. eGFR [ Time Frame: 38 weeks ]
    Mean paired change in eGFR (ml/kg/1.72 m2)

  16. Glycohemoglobin [ Time Frame: 16 weeks ]
    Mean paired change in blood glycohemoglobin (hemoglobin A1C) %

  17. Fasting glucose [ Time Frame: 16 weeks ]
    Mean paired change in fasting glucose (mg/dl)

  18. Troponin I [ Time Frame: 38 weeks ]
    Mean paired change in plasma ultrasensitive troponin I (ng/L)

  19. BNP [ Time Frame: 38 weeks ]
    Mean paired change in plasma B-type natriuretic peptide BNP (pg/ml)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02251431


Contacts
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Contact: Peter A McCullough, MD, MPH 248-444-6905 peteramccullough@gmail.com

Locations
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United States, Texas
Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital Recruiting
Dallas, Texas, United States, 75226
Contact: Laura Clariday, BS    214-820-7224    laura.clariday@bswhealth.org   
Contact: Rebecca Baker, MSN, RN, ACNS-BS    214-820-7965    rebecca.baker2@bswhealth.org   
Sponsors and Collaborators
Baylor Research Institute
Investigators
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Study Chair: Peter A McCullough, MD, MPH Baylor Research Institute

Publications:

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Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT02251431     History of Changes
Other Study ID Numbers: 014-149
D5551L00004/ISSEXEN0013 ( Other Grant/Funding Number: AstraZeneca )
First Posted: September 29, 2014    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: August 2018

Keywords provided by Baylor Research Institute:
diabetes mellitus
chronic kidney disease
diastolic function
cardiac fibrosis
cardiac strain
cardiac biomarker
renal biomarker

Additional relevant MeSH terms:
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Diabetes Mellitus
Kidney Diseases
Diabetes Mellitus, Type 2
Renal Insufficiency, Chronic
Cardio-Renal Syndrome
Ventricular Dysfunction, Left
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Renal Insufficiency
Heart Failure
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists