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

NCT ID: NCT02948777

Last Updated: 2021-11-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2018-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Type 2 Diabetes Mellitus

Keywords

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apolipoprotein, CVD, chylomicrons, evolocumab, kinetics

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Evolocumab

Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks

Group Type EXPERIMENTAL

Evolocumab

Intervention Type DRUG

Interventions

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Evolocumab

Intervention Type DRUG

Other Intervention Names

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Repatha

Eligibility Criteria

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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%.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

77 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Göteborg University

OTHER

Sponsor Role collaborator

Marja-Riitta Taskinen

OTHER

Sponsor Role lead

Responsible Party

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Marja-Riitta Taskinen

Professor, emerita

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Marja-Riitta Taskinen, Prof., PI

Role: PRINCIPAL_INVESTIGATOR

Clinical Research institute Huch, Ltd and University of Helsinki

Jan Boren, Prof., co-PI

Role: PRINCIPAL_INVESTIGATOR

University of Gothenburg and Sahlgrenska University Hospital

Locations

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Helsinki University Hospital, Biomedicum 2U

Helsinki, , Finland

Site Status

Countries

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Finland

References

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Taskinen MR, Bjornson E, Kahri J, Soderlund S, Matikainen N, Porthan K, Ainola M, Hakkarainen A, Lundbom N, Fermanelli V, Fuchs J, Thorsell A, Kronenberg F, Andersson L, Adiels M, Packard CJ, Boren J. Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):962-975. doi: 10.1161/ATVBAHA.120.315446. Epub 2020 Dec 24.

Reference Type RESULT
PMID: 33356392 (View on PubMed)

Taskinen MR, Bjornson E, Andersson L, Kahri J, Porthan K, Matikainen N, Soderlund S, Pietilainen K, Hakkarainen A, Lundbom N, Nilsson R, Stahlman M, Adiels M, Parini P, Packard C, Boren J. Impact of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab on the postprandial responses of triglyceride-rich lipoproteins in type II diabetic subjects. J Clin Lipidol. 2020 Jan-Feb;14(1):77-87. doi: 10.1016/j.jacl.2019.12.003. Epub 2019 Dec 12.

Reference Type RESULT
PMID: 31917184 (View on PubMed)

Zech LA, Grundy SM, Steinberg D, Berman M. Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects. J Clin Invest. 1979 Jun;63(6):1262-73. doi: 10.1172/JCI109421.

Reference Type RESULT
PMID: 221537 (View on PubMed)

Bjornson E, Packard CJ, Adiels M, Andersson L, Matikainen N, Soderlund S, Kahri J, Sihlbom C, Thorsell A, Zhou H, Taskinen MR, Boren J. Investigation of human apoB48 metabolism using a new, integrated non-steady-state model of apoB48 and apoB100 kinetics. J Intern Med. 2019 May;285(5):562-577. doi: 10.1111/joim.12877. Epub 2019 Mar 12.

Reference Type RESULT
PMID: 30779243 (View on PubMed)

Taskinen MR, Matikainen N, Bjornson E, Soderlund S, Inkeri J, Hakkarainen A, Parviainen H, Sihlbom C, Thorsell A, Andersson L, Adiels M, Packard CJ, Boren J. Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy. Diabetologia. 2023 Dec;66(12):2307-2319. doi: 10.1007/s00125-023-06008-0. Epub 2023 Sep 29.

Reference Type DERIVED
PMID: 37775612 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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EVOLKIN

Identifier Type: -

Identifier Source: org_study_id