NCT00116207

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2000

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2000

Completed
5.5 years until next milestone

First Submitted

Initial submission to the registry

June 27, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 28, 2005

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
6.1 years until next milestone

Results Posted

Study results publicly available

January 5, 2016

Completed
Last Updated

July 29, 2016

Status Verified

June 1, 2016

Enrollment Period

9.7 years

First QC Date

June 27, 2005

Results QC Date

January 6, 2014

Last Update Submit

June 30, 2016

Conditions

Diabetic Autonomic Neuropathy

Keywords

Type 1 DiabetesOxidative StressDiabetic ComplicationsNeuropathy

Outcome Measures

Primary Outcomes (1)

  • Global [11C]HED Retention Index (RI)

    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.

    Baseline, 24 months

Secondary Outcomes (3)

  • Global Coronary Flow Reserve as a Measure of Endothelial Function

    Baseline, 24 months

  • Systemic Oxidative Stress

    24 months

  • Inflammation

    24 months

Study Arms (2)

ORAL ANTIOXIDANT

EXPERIMENTAL

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.

Drug: ORAL ANTIOXIDANT

Placebo

PLACEBO COMPARATOR

Placebo administered twice daily.

Drug: ORAL ANTIOXIDANT

Interventions

ORAL ANTIOXIDANTDRUG

Comparison of triple antioxidant combination therapy vs placebo.

Also known as: Allopurinol (300mg daily),, ALA (600mg twice daily), nicotinamide (750 mg twice daily)
ORAL ANTIOXIDANTPlacebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • History of drug or alcohol dependence, heart disease, viral illness, liver disease, advanced kidney disease
  • Pregnant or nursing
  • Severely overweight

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

  • Pop-Busui R, Stevens MJ, Raffel DM, White EA, Mehta M, Plunkett CD, Brown MB, Feldman EL. Effects of triple antioxidant therapy on measures of cardiovascular autonomic neuropathy and on myocardial blood flow in type 1 diabetes: a randomised controlled trial. Diabetologia. 2013 Aug;56(8):1835-44. doi: 10.1007/s00125-013-2942-9. Epub 2013 Jun 6.

    PMID: 23740194DERIVED

MeSH Terms

Conditions

Diabetic NeuropathiesDiabetes Mellitus, Type 1Diabetes Complications

Interventions

AntioxidantsAllopurinolNiacinamide

Condition Hierarchy (Ancestors)

Peripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesDiabetes MellitusEndocrine System DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Biological FactorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesProtective AgentsPhysiological Effects of DrugsSpecialty Uses of ChemicalsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNicotinic AcidsAcids, HeterocyclicPyridinesHeterocyclic Compounds, 1-Ring

Results Point of Contact

Title
Eva L. Feldman, Professor of Internal Medicine
Organization
University of Michigan
efeldman@med.umich.edu
7347637274

Study Officials

  • Eva L Feldman, MD, PhD

    University of Michigan

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

June 27, 2005

First Posted

June 28, 2005

Study Start

January 1, 2000

Primary Completion

September 1, 2009

Study Completion

December 1, 2009

Last Updated

July 29, 2016

Results First Posted

January 5, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will not share

Locations

US(1)