Effects of PCSK9 Inhibition by Evolocumab on Postprandial Lipid Metabolism in Type 2 Diabetes

• Register: ClinicalTrials.gov
• Last refreshed on: 8 November 2021
• Main ID: NCT02948777
• Date of registration: 27/10/2016
• Prospective Registration: No
• Primary sponsor: Marja-Riitta Taskinen
• Public title: Effects of PCSK9 Inhibition by Evolocumab on Postprandial Lipid Metabolism in Type 2 Diabetes
• Scientific title: Effects of PCSK9 Inhibition by Evolocumab on Postprandial Lipid Metabolism in Type 2 Diabetes
• Date of first enrolment: October 2016
• Target sample size: 14
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02948777
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Finland

Contacts

• Name: Marja-Riitta Taskinen, Prof., PI
• Affiliation: Clinical Research institute Huch, Ltd and University of Helsinki

• Name: Jan Boren, Prof., co-PI
• Affiliation: University of Gothenburg and Sahlgrenska University Hospital

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 77 Years
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Evolocumab

Primary Outcome(s)

Mean Total Production of ApoB48 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean LDL FCR of ApoB100 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

LDL Pool Size of ApoB100 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean ApoB Concentration Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean TRL-C Concentration Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Secondary Outcome(s)

IDL Pool Size of ApoB100 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean CM TG-AUC Before and After Evolocumab [Time Frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks]

Mean ApoB48 AUC Before and After Evolocumab [Time Frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks]

Mean CM-apoB48 FCR of ApoB48 Metabolism Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean Postprandial CM of ApoB48 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean ApoB48 Concentration Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean CM TG-iAUC Before and After Evolocumab [Time Frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks]

Mean VLDL1 Triglyceride Production Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean IDL to LDL Transfer of ApoB100 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VLDL2 Triglyceride Total Production Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean Liver Fat Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VLDL2 ApoB100 Production Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean SAT Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VAT Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VLDL1 FCR of triglycerideBefore and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VLDL2 FCR of Triglyceride Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean ApoB48 iAUC Before and After Evolocumab [Time Frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks]

Mean LDL-C Concentration Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean VLDL1 ApoB100 Production Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Mean CM-TG Production of ApoB48 Before and After Evolocumab [Time Frame: Baseline and after 12 weeks]

Secondary ID(s)

EVOLKIN

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Göteborg University

Results

• Results available: Yes
• Date Posted: 11/10/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02948777