Diabetic Autonomic NeuropathyPhase 3NCT00116207

An Intervention Trial for Cardiac Neuropathy in Type 1 Diabetes

A Phase 3 study testing ORAL ANTIOXIDANT in people with Diabetic Autonomic Neuropathy, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Diabetic Autonomic Neuropathy
What is being tested?: ORAL ANTIOXIDANT
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 1 siteUnited States
Study dates: Jan 2000to Dec 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: Oxidative Stress and Cardiovascular Denervation in Diabetes: An Interventional Trial

Conditions: Diabetic Autonomic Neuropathy
Being tested: ORAL ANTIOXIDANT
Keywords: Type 1 Diabetes, Oxidative Stress, Diabetic Complications, Neuropathy
Medical subject headings: Diabetic Neuropathies, Diabetes Mellitus, Type 1, Diabetes Complications

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ORAL ANTIOXIDANTDrug
Also called Allopurinol (300mg daily),, ALA (600mg twice daily), nicotinamide (750 mg twice daily)
Comparison of triple antioxidant combination therapy vs placebo.

Study groups in NCT00116207
Study group	Role	What they receive
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. Receives: Drug: ORAL ANTIOXIDANT
Placebo	Placebo comparator	Placebo administered twice daily. Receives: Drug: ORAL ANTIOXIDANT

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, 24 months

Secondary outcomes (3)

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.
Measured: Baseline, 24 months
Systemic Oxidative Stress
ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection
Measured: 24 months
Inflammation
High Sensitivity CRP (nmol/L)
Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2000Dec 2009

First posted28 Jun 2005 (estimated)
Study startJan 2000
Primary completionSep 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetic Autonomic NeuropathyStudies of the same condition, open and under way.
More trials run by University of MichiganThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00116207
Sponsor's protocol ID: IRB:2002-0460
Status last verified: Jun 2016
First submitted: 27 Jun 2005
Last updated: 29 Jul 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 23740194

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Diabetic Autonomic Neuropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Oxidative Stress and Cardiovascular Denervation in Diabetes: An Interventional Trial
ClinicalTrials.gov ID: NCT00116207
Acronym / sponsor ID: IRB:2002-0460
Conditions: Diabetic Autonomic Neuropathy
Keywords: Type 1 Diabetes, Oxidative Stress, Diabetic Complications, Neuropathy
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: University of MichiganUniversity, hospital or other
Collaborators: Juvenile Diabetes Research Foundation
Study start: Jan 2000
Primary completion: Sep 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 28 Jun 2005 (estimated)
Results: Posted 5 Jan 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ORAL ANTIOXIDANT	Experimental	Drug: ORAL ANTIOXIDANTAllopurinol (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.
Placebo	Placebo comparator	Drug: ORAL ANTIOXIDANTPlacebo administered twice daily.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ORAL ANTIOXIDANTAlso: Allopurinol (300mg daily),, ALA (600mg twice daily), nicotinamide (750 mg twice daily)Comparison of triple antioxidant combination therapy vs placebo.	Drug	ORAL ANTIOXIDANT, Placebo

Primary outcome

Global [11C]HED Retention Index (RI)
Time frame: 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.

3 secondary outcomes

Global Coronary Flow Reserve as a Measure of Endothelial Function
Time frame: Baseline, 24 months
Systemic Oxidative Stress
Time frame: 24 months
Inflammation
Time frame: 24 months

Results and safety

Results posted to the registry on 5 Jan 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ORAL ANTIOXIDANT	22	13
Placebo	22	18

Primary outcome: Global [11C]HED Retention Index (RI)

Time frame: Baseline, 24 months. Mean (Standard Deviation). Unit: Retention index

Measure	ORAL ANTIOXIDANT n = 13	Placebo n = 18
BASELINE	0.081 (0.017)	0.073 (0.016)
24 MONTHS	0.070 (0.018)	0.074 (0.016)

ORAL ANTIOXIDANT vs Placebo: p = 0.32, ANOVA
ORAL ANTIOXIDANT vs Placebo: p = 0.045, ANOVA

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: At each subject visit adverse events were reviewed with the subject.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ORAL ANTIOXIDANT	1 of 22 (4.5%)	18 of 22 (81.8%)	Not reported
Placebo	1 of 22 (4.5%)	21 of 22 (95.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23740194Pop-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.
Individual participant dataSharing planned: No

Related trials for Diabetic Autonomic Neuropathy

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Diabetic Cardiovascular Autonomic Neuropathy, Type 2 Diabetes Mellitus
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Normast3 for Adults With Diabetic Polyneuropathy
Diabete Type 2
Not yet recruiting
Concurrent Training vs Soleus Push-Ups on Neurogenesis-Related Biomarkers in Diabetic Neuropathy Patients
Diabetic Peripheral Neuropathy Type 2
Recruiting
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Neurologic Disorders, Nervous System Diseases
RecruitingPhase 4
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Eva L Feldman, MD, PhD principal investigator

University of Michigan

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ORAL ANTIOXIDANT in people with Diabetic Autonomic Neuropathy, run by University of Michigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Global [11C]HED Retention Index (RI) (time frame: Baseline, 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00116207, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2016.