None listed
Conditions
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.
Interventions
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
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 If a subject is unable to tolerate Nicotinic Acid PR 500mg orally daily, they will be withdrawn for the study.
Sponsors
Professor Gerald Watts
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to 79 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed