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.
- Conditions
- Familial DysbetalipoproteinemiaFredrickson Type III hyperlipoproteinemia1001331710003216
- Registration Number
- NL-OMON49866
- Lead Sponsor
- niversitair Medisch Centrum Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
1. Subjects diagnosed with Familial Dysbetalipoproteinemia; defined as;
*known *2*2 genotype or known dominant APOE mutation genotype (confirmed by
genotyping or isoelectric focusing) and a phenotype of familial
dysbetalipoproteinemia (defined as an ApoB/TC ratio < 0.15, TC > 5 mmol/L and
TG > 3 mmol/L or non-HDL-c/ApoB ratio > 6.55 mmol/g; with or without
medication.
2. If using any lipid lowering treatment: dose must be stable for at least
three months with non-HDL-C levels > 1.6 mmol/L.
3. >=18 or =< 80 years years old (on the day of signing informed consent).
4. Women are postmenopausal and not receiving systemic cyclic estrogen hormone
agonist/antagonist therapy to prevent external effects due to estrogen on
lipoprotein metabolism. 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).
5. Willingness to maintain a stable diet for the duration of the study.
6. Understanding of the study procedures, alternative treatments available, and
risks involved with the study and voluntarily agreement to participate by
giving written informed consent.
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 ((< 1 year before screening) and not discontinued
with PCSK9-inhibitor mAbs due to side effects) to evolocumab or another
PCSK9-inhibitor mAb.
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.
14. Current use or use in the past 3 months of immunosuppressive medication.
15. 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.
16. Active malignancy (<2 year prior to informed consent), except non-melanoma
skin cancer or carcinoma in situ of the cervix.
17. Known infection with Human Immunodeficiency Virus (HIV) or AIDS.
18. Known celiac disease or other disorder associated with significant
intestinal malabsorption, including short-bowel syndrome after intestinal
resection or gastric bypass.
19. Known galactose-intolerance, Lapp-lactase deficiency or glucose-galactose
malabsorption.
20. 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.
21. Current participation or participation in a study with an investigational
compound or device within 30 days of signing informed consent.
22. Any medical, social or physiological circumstance which interferes the
study, based on judgement by the principal investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is non-HDL-C AUC (area under the curve).</p><br>
- Secondary Outcome Measures
Name Time Method