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Trial record 55 of 88 for:    NIDDK endocrine and diabetes | Recruiting, Not yet recruiting, Available Studies

The Impact of Fitness and Mineralocorticoid Receptor Blockade on Vascular Dysfunction in Adults With Type 1 Diabetes (EJB048)

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ClinicalTrials.gov Identifier: NCT03174288
Recruitment Status : Recruiting
First Posted : June 2, 2017
Last Update Posted : June 2, 2017
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Eugene Barrett, University of Virginia

Brief Summary:

In this protocol, 60 subjects with DM1 will be studied at baseline, after 12 weeks of MCR blockade or 12 weeks of exercise, and again after an additional 12 weeks of MCR blockade, exercise or the combination of both interventions. The investigators will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a euglycemic insulin clamp.

We hypothesize that compared to healthy controls, both baseline and insulin-responsive vascular function are impaired throughout the arterial vasculature by DM1 and that exercise training and/or mineralocorticoid receptor (MCR) blockade will improve both baseline and insulin-responsive pan-arterial function.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Other: Exercise Drug: Spironolactone Not Applicable

Detailed Description:

Using non-invasive methods, several small studies have demonstrated conduit artery stiffness and other small studies report impaired brachial artery nitric oxide (NO) release in subjects with type diabetes (DM1). Vascular insulin action (characterized by insulin-induced NO-mediated vasodilation of conduit, resistance or microvascular vessels) has not been studied systematically in DM1. The investigators hypothesize that compared to healthy controls, both baseline and insulin-responsive vascular function are impaired throughout the arterial vasculature by DM1 and that exercise training and/or mineralocorticoid receptor (MCR) blockade will improve both baseline and insulin-responsive pan-arterial function.

In this protocol, 60 subjects with DM1 will be studied at baseline, after 12 weeks of MCR blockade or 12 weeks of exercise, and again after an additional 12 weeks of MCR blockade, exercise or the combination of both interventions. Investigators will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a euglycemic insulin clamp.

This work will: a) identify whether vascular stiffness and indices of NO action are impaired throughout the arterial tree in DM1; b) identify the impact of fitness, MCR blockade or the combination to improve vascular function; and c) introduce a rational paradigm for early, proof-of-concept testing of interventions that may improve vascular health in DM1. While multiple endpoints are measured in the proposed studies, the investigators designate one primary conduit vessel endpoint (augmentation index) and one primary microvascular endpoint (microvascular blood volume by CEU); the studies are powered on these measures. The investigators believe that their laboratories are in a unique position with respect to their demonstrated scientific expertise to deliver this fundamental information.

The study proposed here will be the first to assess whether: 1) basal pan-arterial function including myocardial microvascular function is adversely affected by DM1 ; 2) vascular insulin responsiveness in DM1 is impaired as is seen in DM2 3) exercise training or MCR blockade alone or in combination favorably impacts vascular stiffness or NO-induced relaxation in DM1 in the basal state or in response to insulin. This non-invasive vascular profiling provides a functional "biomarker" of pan-arterial health. As such it could be useful for assessing the impact of specific short-term interventions on critical vascular functions in small scale studies (e.g. MCR blockade, statins, GLP-1R agonists) and thereby provide a rationale for selection of candidate therapies for subsequent larger clinical outcome trials. Additionally, non-invasive assessment of pan-arterial function could provide a platform to identify patients for early or more intensive treatment interventions as part of their care plan.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Impact of Fitness and Mineralocorticoid Receptor Blockade on Vascular Dysfunction in Adults With Type 1 Diabetes
Study Start Date : August 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Exercise alone
24 weeks of exercise treatment
Other: Exercise
24 weeks of exercise treatment

Experimental: spironolactone alone
24 weeks of Spironolactone treatment
Drug: Spironolactone
24 weeks of spironolactone

Experimental: Exercise + Spironolactone
24 weeks of exercise + Spironolactone treatment
Other: Exercise
24 weeks of exercise treatment

Drug: Spironolactone
24 weeks of spironolactone




Primary Outcome Measures :
  1. Augmentation Index-Change from baseline [ Time Frame: 24 weeks ]
    measured at baseline and 24 weeks


Secondary Outcome Measures :
  1. Flow Mediated Dilation-Change from baseline [ Time Frame: 24 weeks ]
    measured at baseline and 24 weeks

  2. Pulse Wave Velocity-Change from baseline [ Time Frame: 24 weeks ]
    measured at baseline and 24 weeks

  3. Post Ischemic Flow Velocity-Change from baseline [ Time Frame: 24 weeks ]
    measured at baseline and 24 weeks

  4. Insulin Sensitivity-Change from baseline [ Time Frame: 24 weeks ]
    measured by euglycemic insulin clamp at baseline and 24 weeks

  5. Microvascular Blood Volume-Change from baseline [ Time Frame: 24 weeks ]
    measured at baseline and 24 weeks



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-50 years
  • BMI ≤30
  • No clinically significant lab values other than those consistent with DM1
  • Subjects will have been on insulin for at least 5 years and HbA1c <9

Exclusion Criteria:

  • Smoking presently or in the past 6 months
  • Medications that affect the vasculature (except ACE or ARB , although they will need to be off these drugs for 2 weeks prior to study).
  • Elevated LDL cholesterol > 160
  • BP <100/60 or >160/90
  • Pulse oximetry <90%
  • Pregnant or breastfeeding
  • History of cardiovascular disease, cerebral vascular disease, peripheral vascular disease, liver disease
  • Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam).
  • Known hypersensitivity to perflutren (contained in Definity)
  • Serum Potassium ≥5.0
  • HbA1c ≥ 9
  • Retinopathy
  • Ketoacidosis within the past year.

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): NCT03174288


Contacts
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Contact: Lee Hartline, MEd 434-924-5247 lmh9d@virginia.edu
Contact: Linda Jahn, RN, MEd 434-924-1134 las6e@virginia.edu

Locations
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United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22906
Contact: Eugene Barrett, MD, PhD    434-924-1175    ejb8x@virginia.edu   
Contact: Zhenqi Liu, MD       zl3e@virginia.edu   
Sponsors and Collaborators
University of Virginia
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Eugene Barrett, MD, PhD University of Virginia, Dept of Endocrinology

Publications:

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Responsible Party: Eugene Barrett, Department of Medicine, Endocrinology, University of Virginia
ClinicalTrials.gov Identifier: NCT03174288     History of Changes
Other Study ID Numbers: 18237
5R01DK101944-03 ( U.S. NIH Grant/Contract )
First Posted: June 2, 2017    Key Record Dates
Last Update Posted: June 2, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Autoimmune Diseases
Immune System Diseases
Spironolactone
Mineralocorticoids
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Hormones