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

Primary Purpose

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

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
BYDUREON
Placebo
Sponsored by
Baylor Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring diabetes mellitus, chronic kidney disease, diastolic function, cardiac fibrosis, cardiac strain, cardiac biomarker, renal biomarker

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Exenatide-extended release

Placebo

Arm Description

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

Matching placebo subcutaneously once per week x 38 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
September 12, 2014
Last Updated
April 24, 2023
Sponsor
Baylor Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02251431
Brief Title
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

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baylor Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exenatide-extended release
Arm Type
Experimental
Arm Description
Exenatide-extended release (BYDUREON™) 2 mg subcutaneously once per week x 38 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo subcutaneously once per week x 38 weeks
Intervention Type
Drug
Intervention Name(s)
BYDUREON
Intervention Description
Exenatide-extended release, Cohorts A and B
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Matching placebo subcutaneous injection
Intervention Description
Cohort A only
Primary Outcome Measure Information:
Title
Galectin-3
Description
Mean change in plasma galectin-3 (pg/ml)
Time Frame
38 weeks
Title
ST2
Description
Mean change in plasma ST2 (pg/ml)
Time Frame
38 weeks
Title
NGAL
Description
Mean change in urine neutrophil gelatinase associated lipocalin (NGAL):creatinine (Cr) ratio
Time Frame
38 weeks
Title
KIM-1
Description
Mean change in urine kidney injury molecule-1 (KIM-1):Cr ratio
Time Frame
38 weeks
Title
L-FABP
Description
Mean change in urine L-type fatty acid binding protein:Cr ratio
Time Frame
38 weeks
Title
IL-18
Description
Mean change in urine interleukin-18:Cr ratio
Time Frame
38 weeks
Title
Alpha GST
Description
Mean change in urine alpha glutathione S-transferase (αGST):Cr ratio
Time Frame
38 weeks
Title
Troponin I
Description
Mean change in plasma ultrasensitive troponin I (pg/ml)
Time Frame
38 weeks
Title
Pi GST
Description
Mean change in pi glutathione S-transferase (piGST):Cr ratio
Time Frame
38 weeks
Title
NAG
Description
Mean change in urine N-acetyl-β-D-glucosaminidase (NAG):Cr ratio
Time Frame
38 weeks
Title
Cystatin-C
Description
Mean paired change in urine cystatin-C:Cr ratio (uCysC:Cr)
Time Frame
38 weeks
Title
BNP
Description
Mean change in plasma B-type natriuretic peptide BNP (pg/ml)
Time Frame
38 weeks
Title
ACR
Description
Mean change in urine albumin:Cr ratio (ACR)
Time Frame
38 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter A McCullough, MD, MPH
Organizational Affiliation
Baylor Research Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Baylor Scott and White Research Institute- Baylor Heart and Vascular Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17239676
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.
Results Reference
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PubMed Identifier
21802579
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.
Results Reference
background
PubMed Identifier
1080957
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.
Results Reference
background
PubMed Identifier
20929995
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.
Results Reference
background
PubMed Identifier
22249510
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.
Results Reference
background
PubMed Identifier
23482076
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.
Results Reference
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PubMed Identifier
20620723
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.
Results Reference
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Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome

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