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Trial record 1 of 2 for:    Recruiting, Not yet recruiting, Available Studies | "Hyperlipoproteinemia Type III"
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Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia (EVOLVE-FD)

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ClinicalTrials.gov Identifier: NCT03811223
Recruitment Status : Not yet recruiting
First Posted : January 21, 2019
Last Update Posted : January 21, 2019
Sponsor:
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
University Medical Center Nijmegen
Information provided by (Responsible Party):
dr.Frank L.J. Visseren, UMC Utrecht

Brief Summary:
Patients with familial dysbetalipoproteinemia (FD) have increased triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), beta VLDL, premature atherosclerosis and cardiovascular disease. They also have a delayed postprandial triglyceride and chylomicron (CM) remnant clearance. Postprandial hypertriglyceridemia is associated with increased vascular risk. Although combination therapy with statin and fibrate is recommended in the treatment of patients with FD, there is still a substantial amount of patient who do not reach their treatment target with this medication. Furthermore no information is available about the postprandial effects of adding evocolumab to standard lipid lowering therapy in FD patients.

Condition or disease Intervention/treatment Phase
Familial Dysbetalipoproteinemia Hyperlipoproteinemia Type III Drug: Evolocumab Auto-Injector [Repatha] Drug: Placebos Phase 4

Detailed Description:
See brief summary

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Crossover Trial to Evaluate the Effects of Evolocumab Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Evolocumab

Arm Intervention/treatment
Experimental: Evolocumab
Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks
Drug: Evolocumab Auto-Injector [Repatha]
Evolocumab 140 mg every 2 weeks for 12 weeks

Placebo Comparator: Placebo
Placebo injection once every 2 weeks for 12 weeks
Drug: Placebos
Placebo subcutaneous injection every 2 weeks for 12 weeks
Other Name: Placebo




Primary Outcome Measures :
  1. AUC (area under the curve) non-HDL-cholesterol [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. Fasting levels, AUC and iAUC of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and ApoB, as well as fasting non-HDL-cholesterol. [ Time Frame: 12 weeks ]
  2. Percentage change from baseline and absolute difference in fasting and post fat load non-HDL-cholesterol, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and ApoB. [ Time Frame: 12 weeks ]
  3. Fasting and post fat load lipoprotein (VLDL1, VLDL2, IDL, LDL, HDL) concentrations and composition (triglycerides, cholesterol, ApoB and apolipoproteins). [ Time Frame: 12 weeks ]
  4. Post fat load ApoB 48-containing lipoprotein concentrations (chylomicrons and chylomicron remnants) and proteins involved in postprandial lipid metabolism. [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients diagnosed with Familial Dysbetalipoproteinemia;

    • ε2ε2 genotype or dominant APOE mutation genotype (confirmed by genotyping or isoelectric focusing) with any lipid-lowering treatment at a stable dose for at least three months and non-HDL-C >1.6 mmol/L or;
    • Patients with ε2ε2 genotype or dominant APOE mutation (confirmed by genotyping or isoelectric focusing) without lipid-lowering treatment and with an ApoB/TC ratio < 0.15.
  2. >18 years old (on the day of signing informed consent).
  3. Women are postmenopausal and not receiving hormone therapy (including cyclic and non-cyclical hormone replacement therapy or any estrogen antagonist/agonist). Postmenopausal status is defined as:

    • no menses for ≥3 years or;
    • no menses for ≥1 year but <3 years and confirmed by FSH levels elevated into the postmenopausal range (15-150 IU/L).
  4. Willingness to maintain a stable diet for the duration of the study.
  5. Understanding of the study procedures, alternative treatments available, and risks involved with the study and voluntarily agreement to participate by giving written informed consent.

Exclusion criteria:

  1. Intolerance, known allergy or hypersensitivity to evolocumab (or other PCSK-9 monoclonal antibodies), latex or any of the components of the medication.
  2. Current or prior exposure to evolocumab or another PCSK9-inhibitor mAb in the past 12 weeks.
  3. Unable or unwilling to drink an oral fat load.
  4. Premenopausal women.
  5. Uncontrolled diabetes as defined by a HbA1c >69 mmol/mol.
  6. BMI >40 kg/m2.
  7. Uncontrolled blood pressure with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg.
  8. Increased hepatic enzymes, defined as alanine transaminase (ALAT) or aspartate transaminase (ASAT) >3 times the ULN, or active liver disease defined as non alcoholic steatohepatitis (NASH), cirrhosis or Child Pugh B and C, or history of chronic active hepatitis B or C; subjects with documented resolution after treatment are permitted.
  9. Impaired renal function, defined by an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2, and/or need of renal placement therapy or other clinically significant renal disease.
  10. (Sub)clinical hypothyroidism defined as TSH >5.0 mcl/U/mL or (sub)clinical hyperthyroidism defined as TSH < 0.35 mcl/U/ml.
  11. Increased levels of creatinine kinase defined as >3 times the ULN.
  12. Increased fasting levels of triglycerides defined as >10 mmol/L.
  13. History of organ transplantation and/or use of immunosuppressive medication.
  14. Use of fish oil or red yeast rice, bempedoic acid, niacin, CETP inhibitors, lomitapide, mipomersen < 6 weeks prior to the study or the use of siRNA targeting PCSK9 inhibitors < 36 weeks prior to the study.
  15. Active malignancy (<2 year prior to informed consent), except non-melanoma skin cancer or carcinoma in situ of the cervix.
  16. Known infection with Human Immunodeficiency Virus (HIV) or AIDS.
  17. Known celiac disease or other disorder associated with significant intestinal malabsorption.
  18. Known galactose-intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
  19. Alcohol use, defined as >14 alcoholic consumptions per week for women and >21 alcohol consumptions per week for men. One alcohol consumption unit is defined as follows: 350 mL beer, 150 mL wine or 45 mL alcohol for mixed drinks.
  20. Current participation or participation in a study with an investigational compound or device within 30 days of signing informed consent.
  21. Any medical, social or physiological circumstance which interferes the study, based on judgement by the principal investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03811223


Contacts
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Contact: Frank LJ Visseren, prof +31 88 7557324 f.l.j.visseren@umcutrecht.nl
Contact: Britt E Heidemann, MD +31 88 75 579 94 b.e.heidemann@umcutrecht.nl

Sponsors and Collaborators
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
University Medical Center Nijmegen
Investigators
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Principal Investigator: Frank LJ Visseren, prof UMC Utrecht

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Responsible Party: dr.Frank L.J. Visseren, prof. dr. F.L.J. Visseren, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03811223     History of Changes
Other Study ID Numbers: UMCU-VASC-CO-002
First Posted: January 21, 2019    Key Record Dates
Last Update Posted: January 21, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Currently, there is no plan to make individual participant data available to other researchers, but this is possible in the future.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by dr.Frank L.J. Visseren, UMC Utrecht:
Postprandial hyperlipidemia
Evolocumab
PCSK9 monoclonal antibody
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type III
Hyperlipoproteinemias
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Evolocumab
Antibodies, Monoclonal
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Immunologic Factors
Physiological Effects of Drugs