Trial Outcomes & Findings for An Intervention Trial for Cardiac Neuropathy in Type 1 Diabetes (NCT NCT00116207)

NCT ID: NCT00116207

Last Updated: 2016-07-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 44 participants
• Primary outcome timeframe: Baseline, 24 months
• Results posted on: 2016-07-29

Participant Flow

Participant milestones

Measure	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	Placebo Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Overall Study STARTED	22	22
Overall Study COMPLETED	13	18
Overall Study NOT COMPLETED	9	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Intervention Trial for Cardiac Neuropathy in Type 1 Diabetes

Baseline characteristics by cohort

Measure	ORAL ANTIOXIDANT n=22 Participants Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=22 Participants Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	44 years STANDARD_DEVIATION 12 • n=5 Participants	47 years STANDARD_DEVIATION 10 • n=7 Participants	46 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	ORAL ANTIOXIDANT n=13 Participants Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=18 Participants Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Global [11C]HED Retention Index (RI) BASELINE	0.081 Retention index Standard Deviation 0.017	0.073 Retention index Standard Deviation 0.016
Global [11C]HED Retention Index (RI) 24 MONTHS	0.070 Retention index Standard Deviation 0.018	0.074 Retention index Standard Deviation 0.016

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	ORAL ANTIOXIDANT n=13 Participants Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=18 Participants Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Global Coronary Flow Reserve as a Measure of Endothelial Function BASELINE	2.95 ratio (rest:stress) Standard Deviation 1.32	2.94 ratio (rest:stress) Standard Deviation 1.70
Global Coronary Flow Reserve as a Measure of Endothelial Function 24 MONTH	3.02 ratio (rest:stress) Standard Deviation 1.82	3.22 ratio (rest:stress) Standard Deviation 0.85

SECONDARY outcome

Timeframe: 24 months

ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection

Outcome measures

Measure	ORAL ANTIOXIDANT n=13 Participants Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=18 Participants Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Systemic Oxidative Stress	2.92 ng/G creatinine Standard Deviation 1.99	2.09 ng/G creatinine Standard Deviation 1.12

SECONDARY outcome

Timeframe: 24 months

High Sensitivity CRP (nmol/L)

Outcome measures

Measure	ORAL ANTIOXIDANT n=13 Participants Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=18 Participants Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Inflammation	17.51 nmol/L Standard Deviation 20.19	16.95 nmol/L Standard Deviation 18.38

Adverse Events

ORAL ANTIOXIDANT

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	ORAL ANTIOXIDANT n=22 participants at risk Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=22 participants at risk Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death	0.00% 0/22 • At each subject visit adverse events were reviewed with the subject.	4.5% 1/22 • Number of events 1 • At each subject visit adverse events were reviewed with the subject.
Psychiatric disorders Suicide Attempt	4.5% 1/22 • Number of events 1 • At each subject visit adverse events were reviewed with the subject.	0.00% 0/22 • At each subject visit adverse events were reviewed with the subject.

Other adverse events

Measure	ORAL ANTIOXIDANT n=22 participants at risk Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo	Placebo n=22 participants at risk Placebo administered twice daily. ORAL ANTIOXIDANT: Comparison of triple antioxidant therapy to placebo
General disorders Non-Serious Adverse Events	81.8% 18/22 • Number of events 137 • At each subject visit adverse events were reviewed with the subject.	95.5% 21/22 • Number of events 141 • At each subject visit adverse events were reviewed with the subject.

Additional Information

Eva L. Feldman, Professor of Internal Medicine

University of Michigan

Phone: 7347637274

Email: efeldman@med.umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place