None listed
Conditions
Brief summary
The aim is to carry out a cross-over study to determine if Nicotinic acid prolonged release (Nicotinic acid PR) has beneficial effects on postprandial lipid and lipoprotein concentrations and apoprotein transport rates in patients with type 2 diabetes (T2DM) who are at high risk of cardiovascular disease (CVD). In these participants, Nicotinic acid PR will be used in combination with their current optimal dose statin therapy.
Interventions
Nicotinic acid prolonged release (PR), starting dose of 1000mg orally daily (od), increasing to 2000mg od after 4 weeks and maintaining this dose for the next 8 weeks (i.e. 12 week treatment period in total). This is a cross over study, therefore Nicotinic acid PR will be taken for 1 of the two 12 week treatment periods. There will be a 3 week washout period inbetween the 2 treatment periods. The second treatment period is a no treatment period. Nicotinic acid will be administered as an oral tab
Nicotinic acid prolonged release (PR), starting dose of 1000mg orally daily (od), increasing to 2000mg od after 4 weeks and maintaining this dose for the next 8 weeks (i.e. 12 week treatment period in total). This is a cross over study, therefore Nicotinic acid PR will be taken for 1 of the two 12 week treatment periods. There will be a 3 week washout period inbetween the 2 treatment periods. The second treatment period is a no treatment period. Nicotinic acid will be administered as an oral tablet. Rosuvastatin, 5-40mg. All participants will be on stable dose concomittant Rosuvastatin for 6 weeks prior to the study and for the duration of the study. Rosuvastatin will be administered as an oral tablet at an optimal dose to acheive an low density lipoprotein-cholesterol of less than 2.5mmol/L. Immediately following a high fat test meal, intravenous D3-leucine stable isotope and two oral vitamin A capsules (50,000U each) will be used as kinetic tracers of lipoprotien metabolism. These will be given twice, that is once only on each stable isotope day at the end of each (two) treatment periods.
Sponsors
Professor Gerald Watts
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Non-smoking men aged 18-75 years with a Body Mass Index (BMI) <40kg/m2 and type 2 diabetes will be recruited. Patients will be treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) at a stable dose for greater than or equal to 6 weeks and will have attained a target low density lipoprotein (LDL)-cholesterol of <2.5mmol/L, fasting triglyceride <4.5mmol/L and/or high density lipoprotien (HDL)-cholesterol greater than or equal to 1.0mmol/L.
Exclusion criteria
Subjects with genetic hyperlipidemia (e.g. familial hyperlipidaemia (FH), type III hyperlipidaemia), proteinuria, hypothyroidism, cholelithiasis, excess alcohol intake (>30g/day), haemoglobin A1c (HbA1c) >8.5%, daytime insulin treatment, uncontrolled hypertension >150/90mmHg; fasting cholesterol >6.0mmol/L or triglyceride >4.5mmol/L, creatinemia (>150umol/L), hepatic dysfunction ( aspartate ransaminase (AST) or alanine transaminase (ALT) >3x upper limit of normal (ULN), abnormal thyroid function, muscle disorders or creatinine kinase >3xULN; major systemic illness, use of steroids or other agents that may influence lipid metabolism, including fish oils, cardiovascular event within the last 6 months, anaemia or history of gout, or gastric disorders; patients on hypocaloric diets, lactose intolerance or intolerance to cream and eggs.
Outcome results
None listed