Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12606000466549
Ethics application status
Approved
Date submitted
8/11/2006
Date registered
9/11/2006
Date last updated
29/05/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to investigate the effect of taking Nicotinic Acid Prolonged Release on abnormal artery blood vessel function in people with Type 2 diabetes who are on best-dose treatment with statin medications.
Scientific title
Effect of Nicotinic Acid Prolonged Release on endothelial dysfunction in subjects with Type 2 diabetes mellitus who are receiving optimal dose statin therapy
Universal Trial Number (UTN)
Trial acronym
NAPS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Subjects with Type 2 diabetes mellitus who are receiving optimal dose statin therapy. 1443 0
Condition category
Condition code
Metabolic and Endocrine 1538 1538 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
23 week randomised end-point blinded, controlled parallel study comparing Nicotinic Acid Prolonged Release (PR) orally daily (titrated to a maximum dose of 1500mg) with a No Nicotinic Acid PR group. Nicotinic Acid PR will commence at 500mg orally daily at bedtime and be titrated at weeks 5 and 9 to 1000mg and 1500mg respectively, according to the subjects maximum tolerated dose. The maximum tolerated dose will not exeed 1500mg orally daily. If a subject is unable to tolerate an increased dose level due to skin flushing episodes, their dose will be decreased back to the preceding dosel level. If a subject is unable to tolerate Nicotinic Acid PR 500mg orally daily, they will be withdrawn for the study.
Intervention code [1] 1435 0
Treatment: Drugs
Comparator / control treatment
The No Nicotinic Acid PR group are subjects with type 2 diabetes on optimal dose statin and reduced endothelial dysfunction as for the Nicotinic Acid PR group.
Control group
Active

Outcomes
Primary outcome [1] 2122 0
Brachial artery ultrasound: change in % FMD (flow mediated dilatation, endotheilium-mediated)
Timepoint [1] 2122 0
Measured at randomisation (week 1) and study end (week 21).
Secondary outcome [1] 3667 0
1. Forearm plethysmography: changes in forearm blood flow.
Timepoint [1] 3667 0
Measured at randomisation (week 1) and study end (week 21).
Secondary outcome [2] 3668 0
2. Non-invasive measures of arterial stiffness (applanation tonometry and arterial pusle wave analysis; Small and larger artery compliance, Augmentation index, and Pulse Wave Velocity).
Timepoint [2] 3668 0
Measured at randomisation (week 1) and study end (week 21).
Secondary outcome [3] 3669 0
3. Biological markers.
Timepoint [3] 3669 0
Measured at randomisation (week 1) and study end (week 21).

Eligibility
Key inclusion criteria
Type 2 diabetes; treatment with HMG-CoA reductase inhibitor (statin) at a stable dose for >=6 weeks; treatment with aspirin therapy (100mg orally daily) for >=2 weeks at screening brachial artery ultrasound; fasting LDL-cholesterol <2.5mmol/L; HDL-cholesterol <=1.5mmol/L, brachial artery FMD <=5.50% on screening ultrasound.
Minimum age
40 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
At screening: daytime insulin treatment (nocte insulin permitted); uncontrolled hyperglycaemia (HbA1c level >8.5%); uncontrolled hypertension (resting BP >150/90mmHg); total fasting cholesterol >=6.0mmol/L or triglycerides >=4.5mmol/L; hypersensitivity to nicotinic acid; hypersensitivity to aspirin therapy; treatment with other lipid-regulating medications (eg. fibrate, ezetimibe, cholestyramine, niacin, fish oil) or with CoQ supplements (within previous 6 weeks); current treatment with warfarin, nitrate or PDE5-inhibitor (eg. sildenafil); history peptic ulcer disease; history of arterial bleeding; recent cardiovascular event (within previous 6 months); atrial fibrillation or other significant dysrhythmia; significantly abnormal renal (creatinine >150ummol/L), liver (ALT >3 times ULN) or thyroid function; Significantly abnormal creatine kinase >3 times ULN; significant anaemia; history of gout; current smoker (previous 6 months); ethanol intake>21 standard drinks/week; significant substance abuse, psychiatric illness or likely poor compliance with study protocol; any other serious illness (eg. cancer) or likelihood of not completing study; technical difficulty with obtaining ultrasound scan of sufficient quality; weight>150kg.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involves contacting the person holding the allocation schedule and who is not involved in the study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation sequence generated by computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1677 0
University
Name [1] 1677 0
School of Medicine and Pharmacology
Country [1] 1677 0
Australia
Funding source category [2] 1678 0
Hospital
Name [2] 1678 0
Royal Perth Hospital
Country [2] 1678 0
Australia
Primary sponsor type
Individual
Name
Professor Gerald Watts
Address
School of Medicine and Pharmacology, Royal Perth Hospital, Rear 50 Murray Street, Perth, WA 6000
Country
Australia
Secondary sponsor category [1] 1479 0
None
Name [1] 1479 0
Nil
Address [1] 1479 0
Country [1] 1479 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3123 0
School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia
Ethics committee address [1] 3123 0
Ethics committee country [1] 3123 0
Australia
Date submitted for ethics approval [1] 3123 0
Approval date [1] 3123 0
17/07/2006
Ethics approval number [1] 3123 0
EC2006/122

Summary
Brief summary
People with diabetes and atherogenic dyslipidaemia who are treated with statin medication may still be at increased risk of cardiovascular disease and may require combination lipid regulating therapy to further reduce their risk. Endothelial dysfunction and increased arterial stiffness are present in early diabetic vascular disease and may be useful surrogate endpoints for cardiovascular risk. This 23 week, randomised single-blind, controlled, parallel group study in 50 participants with diabetes who have endothelial dysfunction despite optimal statin therapy, aims to investigate whether the addition of Nicotinic Acid Prolonged Release (titrated to a maximum dose of 1500mg orally daily) compared to a control group of no Nicotinic Acid Prolonged Release (Nicotinic Acid PR) improves endothelial dysfunction.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27369 0
Address 27369 0
Country 27369 0
Phone 27369 0
Fax 27369 0
Email 27369 0
Contact person for public queries
Name 10624 0
Sandra Hamilton
Address 10624 0
Level 3
School of Medicine and Pharmacology
Royal Perth Hospital
Rear 50 Murray Street
Perth, WA 6001
Country 10624 0
Australia
Phone 10624 0
+61 8 92240318
Fax 10624 0
+61 8 92240243
Email 10624 0
[email protected]
Contact person for scientific queries
Name 1552 0
Professor Gerald Watts
Address 1552 0
Level 4
School of Medicine and Pharmacology
Royal Perth Hospital
Rear 50 Murray Street
Perth, WA 6001
Country 1552 0
Australia
Phone 1552 0
+61 8 92240252
Fax 1552 0
+61 8 92240246
Email 1552 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.