Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01019486
First received: November 23, 2009
Last updated: February 15, 2012
Last verified: February 2012
  Purpose

Cardiovascular disease (CVD) remains the major cause of mortality and morbidity in both type 1 (T1D) and type 2 (T2D) diabetes patients; modifications of traditional CVD risk factors have had a limited impact. This project called Regadenoson Blood flow in Type 1 Diabetes (RABIT1D) and is proposed as a sub-study of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study, which has established a unique cohort of 656 T1D patients (age 20-55, minimal diabetes duration of 10 yrs) and 764 non-diabetic controls. This cohort is being followed for progression of coronary artery calcification (CAC) measured using the electron beam tomography (EBT) for development of clinical CVD. Participants have been well characterized during the baseline examination (4/00-3/02) and two follow-up re-examinations 3 and 6 years later. The study has provided important insights into the risk factors and possible prevention of premature CVD in T1D. We are proposing assess a subset of this population to determine vasodilatory reserve as it relates to early coronary atherosclerosis in T1D.

Hypothesis: that myocardial blood imaging (MBF) reserve can be measured in Type 1 DM using regadenoson stress cardiac magnetic resonance and that significantly reduced MBF is a marker of extensive atherosclerotic disease correlated to coronary arterial calcification, plaque formation and impaired vasodilatory reserve.

Specific Aims:

  1. Determine the relationship between myocardial perfusion index (previously determined), regional CBF and invasively measured coronary flow reserve
  2. Measure coronary blood flow using regadenoson stress CMR and determine the myocardial blood flow reserve in type 1 DM subjects compared to non-diabetic controls.
  3. Determine the relationship between CBF reserve in vascular distributions to the degree of coronary arterial calcification.
  4. Determine the severity of CBF blood flow reduction and the relationship to perfusion reserve measured by invasive coronary Doppler flow-wire under regadenoson between in type 1 DM subjects compared to non-diabetic controls.

Condition Intervention Phase
Coronary Artery Disease
Type 1 Diabetes Mellitus
Procedure: Regadenoson myocardial perfusion imaging
Procedure: Cardiac MRI coronary blood flow measurement
Drug: Coronary artery flow reserve (CFR) measurement
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • A significant difference of measured coronary blood flow assessment with regadenoson stress by cardiac MRI between non-diabetic and type 1 diabetic subjects. [ Time Frame: 12-18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measured coronary blood flow is directly correlated with coronary flow reserve measured invasively in the cardiac catheterization laboratory after regadenoson pharmacologic stress. [ Time Frame: 12-18 months ] [ Designated as safety issue: Yes ]

Enrollment: 26
Study Start Date: November 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Type 1 Diabetic subjects
Stratified by coronary calcium score of below 100 or greater than or equal to an Agaston score of 100.
Procedure: Regadenoson myocardial perfusion imaging
Myocardial perfusion imaging at rest and following 400mcg Regadenoson IV bolus pharmacologic stress with 30 mCi of Tc-99m sestamibi injected at both but the studies performed 48 hours apart.
Other Names:
  • Cardiolite (sestamibi)
  • Regadenoson (Lexiscan)
Procedure: Cardiac MRI coronary blood flow measurement
CMR assessment of stress myocardial perfusion and blood flow after 400 mcg Regadenoson pharmacologic using gadolinium contrast(gadoteridol) 0.05mmole/kg at stress and rest.
Other Names:
  • Prohance (Gadoteridol)
  • Regadenoson (Lexiscan)
Drug: Coronary artery flow reserve (CFR) measurement
CFR will be measured in abnormal coronary distribution identified by myocardial perfusion images or CMR measured blood flow. This will use the Volcano ComboMap to assess artery plaque and diameter with flow velocity in response to vasodilation using 400mcg IV bolus of Regadenoson. The CFR will be compared to normal regions. The ratio of abnormal top normal coronary distribution will be calculated for flow reserve.
Other Names:
  • Volcano ComboMap
  • Regadenson (Lexiscan)
Active Comparator: Nondiabetic
Higher risk non -diabetic control with calcium score greater than 100.
Procedure: Regadenoson myocardial perfusion imaging
Myocardial perfusion imaging at rest and following 400mcg Regadenoson IV bolus pharmacologic stress with 30 mCi of Tc-99m sestamibi injected at both but the studies performed 48 hours apart.
Other Names:
  • Cardiolite (sestamibi)
  • Regadenoson (Lexiscan)
Procedure: Cardiac MRI coronary blood flow measurement
CMR assessment of stress myocardial perfusion and blood flow after 400 mcg Regadenoson pharmacologic using gadolinium contrast(gadoteridol) 0.05mmole/kg at stress and rest.
Other Names:
  • Prohance (Gadoteridol)
  • Regadenoson (Lexiscan)
Drug: Coronary artery flow reserve (CFR) measurement
CFR will be measured in abnormal coronary distribution identified by myocardial perfusion images or CMR measured blood flow. This will use the Volcano ComboMap to assess artery plaque and diameter with flow velocity in response to vasodilation using 400mcg IV bolus of Regadenoson. The CFR will be compared to normal regions. The ratio of abnormal top normal coronary distribution will be calculated for flow reserve.
Other Names:
  • Volcano ComboMap
  • Regadenson (Lexiscan)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Inclusion Criteria Nondiabetic controls High-risk (n=5)

    1. Completed visit 6yr f/u CACTI Trial
    2. No history of previous MI, revascularization or angina
    3. CAC > 100
    4. Stratified random sample to reflect age-sex- distribution of the high risk diabetic group T1Diabetic subjects High-risk group (n= 10)
    1. Completed visit 6yr f/u CACTI Trial
    2. No history of previous MI, revascularization or angina
    3. CAC > 100
    4. preferably MPR of > 1.5 T1Diabetic subjects Lower-risk group (n= 10)
    1. Completed visit 1.A and 1.B CACTI Trial
    2. No history of previous MI, revascularization or angina
    3. CAC < 100

      Exclusion Criteria:

    2. Exclusion Criteria:

    1. Pregnant or lactating women, women who plan to become pregnant
    2. Claustrophobia
    3. Moderate or severe congestive heart failure at baseline, LVEF < 25%
    4. Uncontrolled hypertension
    5. Unwillingness to complete all components of the study
    6. Significant CAD or prior revascularization
    7. Smoker
    8. Subject cannot have >50% reduction in lumen diameter of left main coronary artery
    9. Asthma requiring daily bronchodilators
    10. Methylxanthine therapy
    11. Moderate to severe renal insufficiency: GFR < 40 mL/min
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01019486

Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80045
University of Colorado Denver
Aurora, Colorado, United States, 80045
University Hospital, the University of Colorado Health Sciences Center
Denver, Colorado, United States, 80262
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Robert A. Quaife, M.D University of Colorado, Denver
  More Information

Publications:

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01019486     History of Changes
Other Study ID Numbers: IND 105221
Study First Received: November 23, 2009
Last Updated: February 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Myocardial blood flow
Cardiac magnetic resonance imaging
Myocardial perfusion imaging
Coronary artery flow reserve
Regadenoson

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 1
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Regadenoson
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014