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

NCT ID: NCT02251431

Last Updated: 2023-05-17

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2019-12-31

Brief Summary

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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

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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).

Conditions

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Type 2 Diabetes Mellitus Chronic Kidney Disease Left Ventricular Diastolic Dysfunction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Exenatide-extended release

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

Group Type EXPERIMENTAL

BYDUREON

Intervention Type DRUG

Exenatide-extended release, Cohorts A and B

Placebo

Matching placebo subcutaneously once per week x 38 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Cohort A only

Interventions

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BYDUREON

Exenatide-extended release, Cohorts A and B

Intervention Type DRUG

Placebo

Cohort A only

Intervention Type DRUG

Other Intervention Names

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Matching placebo subcutaneous injection

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baylor Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter A McCullough, MD, MPH

Role: STUDY_CHAIR

Baylor Research Institute

Locations

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

Dallas, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17239676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21802579 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1080957 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20929995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22249510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23482076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20620723 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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D5551L00004/ISSEXEN0013

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

014-149

Identifier Type: -

Identifier Source: org_study_id

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