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

NCT03174288 | Completed

• 2 other identifiers: 182375R01DK101944-03
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Augmentation Index-Change from baseline

  measured at baseline and 24 weeks

  24 weeks

Secondary Outcomes (5)

• Flow Mediated Dilation-Change from baseline

  24 weeks

• Pulse Wave Velocity-Change from baseline

  24 weeks

• Post Ischemic Flow Velocity-Change from baseline

  24 weeks

• Insulin Sensitivity-Change from baseline

  24 weeks

• Microvascular Blood Volume-Change from baseline

  24 weeks

Study Arms (3)

Exercise alone

EXPERIMENTAL

24 weeks of exercise treatment

Other: Exercise

spironolactone alone

EXPERIMENTAL

24 weeks of Spironolactone treatment

Drug: Spironolactone

Exercise + Spironolactone

EXPERIMENTAL

24 weeks of exercise + Spironolactone treatment

Other: Exercise; Drug: Spironolactone

Interventions

Exercise OTHER

24 weeks of exercise treatment

Exercise + Spironolactone; Exercise alone

Spironolactone DRUG

24 weeks of spironolactone

Exercise + Spironolactone; spironolactone alone

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22906, United States

Location

Related Publications (58)

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MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Exercise; Spironolactone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Eugene Barrett, MD, PhD

  University of Virginia, Dept of Endocrinology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Medicine, Endocrinology

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: June 2, 2017
• Study Start: August 1, 2015
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: December 18, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)