Diabetic Autonomic Neuropathy
Conditions
Keywords
Type 1 Diabetes, Oxidative Stress, Diabetic Complications, Neuropathy
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.
Interventions
DRUGORAL ANTIOXIDANT
Comparison of triple antioxidant combination therapy vs placebo.
Sponsors
Juvenile Diabetes Research Foundation
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global [11C]HED Retention Index (RI) | Baseline, 24 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Global Coronary Flow Reserve as a Measure of Endothelial Function | Baseline, 24 months | 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 | 24 months | ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection |
| Inflammation | 24 months | High Sensitivity CRP (nmol/L) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ORAL ANTIOXIDANT Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally
ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo | 22 |
| Placebo Placebo administered twice daily.
ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | Placebo | Total | ORAL ANTIOXIDANT |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 44 Participants | 22 Participants |
| Age, Continuous | 47 years STANDARD_DEVIATION 10 | 46 years STANDARD_DEVIATION 11 | 44 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 22 participants | 44 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 13 Participants | 9 Participants |
| Sex: Female, Male Male | 18 Participants | 31 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 22 | 21 / 22 |
| serious Total, serious adverse events | 1 / 22 | 1 / 22 |
Outcome results
Primary
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.
Time frame: Baseline, 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORAL ANTIOXIDANT | Global [11C]HED Retention Index (RI) | BASELINE | 0.081 Retention index | Standard Deviation 0.017 |
| ORAL ANTIOXIDANT | Global [11C]HED Retention Index (RI) | 24 MONTHS | 0.070 Retention index | Standard Deviation 0.018 |
| Placebo | Global [11C]HED Retention Index (RI) | BASELINE | 0.073 Retention index | Standard Deviation 0.016 |
| Placebo | Global [11C]HED Retention Index (RI) | 24 MONTHS | 0.074 Retention index | Standard Deviation 0.016 |
Comparison: BASELINEp-value: 0.32ANOVA
Comparison: 24-MONTHp-value: 0.045ANOVA
Secondary
Global Coronary Flow Reserve as a Measure of Endothelial Function
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.
Time frame: Baseline, 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ORAL ANTIOXIDANT | Global Coronary Flow Reserve as a Measure of Endothelial Function | BASELINE | 2.95 ratio (rest:stress) | Standard Deviation 1.32 |
| ORAL ANTIOXIDANT | Global Coronary Flow Reserve as a Measure of Endothelial Function | 24 MONTH | 3.02 ratio (rest:stress) | Standard Deviation 1.82 |
| Placebo | Global Coronary Flow Reserve as a Measure of Endothelial Function | BASELINE | 2.94 ratio (rest:stress) | Standard Deviation 1.7 |
| Placebo | Global Coronary Flow Reserve as a Measure of Endothelial Function | 24 MONTH | 3.22 ratio (rest:stress) | Standard Deviation 0.85 |
Comparison: BASELINEp-value: 0.52ANOVA
Comparison: 24 MONTHp-value: 0.82ANOVA
Secondary
Inflammation
High Sensitivity CRP (nmol/L)
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ORAL ANTIOXIDANT | Inflammation | 17.51 nmol/L | Standard Deviation 20.19 |
| Placebo | Inflammation | 16.95 nmol/L | Standard Deviation 18.38 |
Comparison: 24 MONTHp-value: 0.83ANOVA
Secondary
Systemic Oxidative Stress
ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ORAL ANTIOXIDANT | Systemic Oxidative Stress | 2.92 ng/G creatinine | Standard Deviation 1.99 |
| Placebo | Systemic Oxidative Stress | 2.09 ng/G creatinine | Standard Deviation 1.12 |
Comparison: 24 MONTHp-value: 0.24ANOVA