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An Intervention Trial for Cardiac Neuropathy in Type 1 Diabetes

This study has been completed.
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Rodica Pop-Busui, University of Michigan Identifier:
First received: June 27, 2005
Last updated: June 30, 2016
Last verified: June 2016
The focus of this project is cardiovascular diabetic autonomic neuropathy (DAN). DAN affects the nerves that control heart rate and blood flow to the heart in people with diabetes. DAN may cause problems with the rhythm of the heartbeat or decrease blood flow to the heart. Three medications will be tested for their effectiveness in DAN.

Condition Intervention Phase
Diabetic Autonomic Neuropathy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oxidative Stress and Cardiovascular Denervation in Diabetes: An Interventional Trial

Resource links provided by NLM:

Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Global [11C]HED Retention Index (RI) [ Time Frame: Baseline, 24 months ] [ Designated as safety issue: No ]

    Distal defects in [11C]meta-hydroxyephedrine ([11C]HED) retention involving at least 10 % of the left ventricle was used to define Cardiac Autonomic Neuropathy (CAN). The retention index (RI) is the unit of measure and is expressed as [11C]HEDblood min -1[ml tissue]-1

    PET Data of Randomized Subjects at Baseline and 24-Months

    The primary outcome was the change in the global [11C]HED RI = measure of cardiac innervation at 24 months in participants taking the active drug compared with those on placebo.

Secondary Outcome Measures:
  • Global Coronary Flow Reserve as a Measure of Endothelial Function [ Time Frame: Baseline, 24 months ] [ Designated as safety issue: No ]
    global myocardial blood flow reserve as a measure of endothelial function. Measured by PET using [13N]ammonia at rest and during adenosine stimulated coronary vasodilation.

  • Systemic Oxidative Stress [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection

  • Inflammation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    High Sensitivity CRP (nmol/L)

Enrollment: 44
Study Start Date: January 2000
Study Completion Date: December 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally These drugs were given together as a combination and not as individual treatment.
Comparison of triple antioxidant combination therapy vs placebo.
Other Names:
  • Allopurinol (300mg daily),
  • ALA (600mg twice daily)
  • nicotinamide (750 mg twice daily)
Placebo Comparator: Placebo
Placebo administered twice daily.
Comparison of triple antioxidant combination therapy vs placebo.
Other Names:
  • Allopurinol (300mg daily),
  • ALA (600mg twice daily)
  • nicotinamide (750 mg twice daily)


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Type 1 diabetes
  • A1C <9%
  • Mild neuropathy
  • Mild retinopathy
  • Mild nephropathy

Exclusion Criteria:

  • History of drug or alcohol dependence, heart disease, viral illness, liver disease, advanced kidney disease
  • Pregnant or nursing
  • Severely overweight
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00116207

United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Juvenile Diabetes Research Foundation
Principal Investigator: Eva L Feldman, MD, PhD University of Michigan
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Rodica Pop-Busui, Associate Professor, University of Michigan Identifier: NCT00116207     History of Changes
Other Study ID Numbers: IRB:2002-0460 
Study First Received: June 27, 2005
Results First Received: January 6, 2014
Last Updated: June 30, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of Michigan:
Type 1 Diabetes
Oxidative Stress
Diabetic Complications

Additional relevant MeSH terms:
Diabetic Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nicotinic Acids
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances
Hypolipidemic Agents
Lipid Regulating Agents
Vasodilator Agents processed this record on October 21, 2016