Effects of PCSK9 Inhibition by Evolocumab on Postprandial Lipid Metabolism in Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Evolocumab
Intervention MeSH terms: Evolocumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 77 Years
Healthy volunteers: No
Keywords: apolipoprotein, CVD, chylomicrons, evolocumab, kinetics

Summary:

      Postprandial lipemia is highly prevalent in type 2 diabetes subjects even with normal fasting
      triglyceride values. Humans are mostly in a postprandial rather than in a fasting state and
      therefore non-fasting triglyceride values reflect more accurately the continuous exposure of
      arterial wall to the substantial cholesterol load from remnant particles. Evolocumab lowers
      blood LDL-cholesterol. This study evaluates the effect of evolocumab on postprandial lipid
      metabolism in type 2 diabetes. All participants in this study receive evolocumab treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female (non-fertile or using a medically approved birth control method)
             overweight/obese subjects with Type 2 Diabetes Mellitus treated with lifestyle
             counselling and a stable metformin dose for at least three months

          -  age 18-77 yrs.

          -  body mass index 25-40 kg/m2

          -  triglycerides between 1.5-4.5 mmol/L and low-density-lipoprotein cholesterol >1.8 but
             ≤4.0 mmol/L (on Atorvastatin 20 mg/day)

          -  glycohemoglobin: ≤9%.

          -  Each patient will attend a pre-screening visit (at week -5) where eligibility criteria
             will be evaluated. If the patient uses another statin than atorvastatin (20 mg) at
             screening visit the used statin is stopped and atorvastatin 20 mg will be initiated.
             If the patient is not using any statin, atorvastatin 20 mg will be initiated and the
             lipid values will be checked after 4 weeks when all inclusion/exclusion criteria will
             be assessed.

        Exclusion Criteria:

          -  Type 1 diabetes

          -  apolipoprotein E2/2 phenotype

          -  alanine transaminase / aspartate transaminase > 3× upper limit of normal

          -  creatinine kinase>3× upper limit of normal

          -  glomerular filtration rate <60 ml/min

          -  clinically significant thyroid-stimulating hormone outside the normal range

          -  body mass index >40 kg/m2

          -  glycohemoglobin > 9.0 %

          -  fasting triglycerides > 4.5 mmol/l

          -  total cholesterol > 7.0 mmol/l

          -  positive urine or serum pregnancy test

          -  untreated or inadequately treated hypertension defined as blood pressure >160 mmHg
             systolic and/or >105 mmHg diastolic, use of thiazide diuretics at a dose of ≥25 mg/day

          -  subject not on a stable dose of atorvastatin (20 mg/ day before randomization)

          -  lipid-lowering drugs other than statins within 3 months

          -  any other diabetes medication except diet + metformin

          -  history/diagnosis of diabetes nephropathy / retinopathy

          -  current smoking

          -  weekly alcohol use over 24 doses for men and 16 for women

          -  history of myocardial infarction, acute coronary syndrome or coronary
             revascularization (percutaneous coronary intervention or coronary artery bypass
             grafting) within the last 6 mos.

          -  planned revascularization (eg coronary artery bypass grafting, percutaneous coronary
             intervention, carotid or peripheral revascularization procedures) within 3 months of
             screening

          -  New York Heart Association class III/IV congestive heart failure persisting despite
             treatment

          -  history of hemorrhagic stroke

          -  hypersensitivity to (evolocumab or) any of the excipients found in the drug product

          -  use of estrogen therapy

          -  current use of antithrombotic or anticoagulant therapy

          -  known bleeding tendency that would be an contraindication to heparin test

          -  history of cancer within the past 5 years (except for adequately treated basal cell
             skin cancer, squamous cell skin cancer or in situ cervical cancer)

          -  women of childbearing potential not protected by effective birth control method and/or
             not willing to be tested for pregnancy

          -  patient considered by the investigator or any sub-investigator as inappropriate for
             this study for any reason