Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

What this study is about

Lipoprotein lipase (LPL) is an enzyme that plays an important role in removing triglycerides (TG) (molecules that transport dietary fat) from the blood. Patients with LPL deficiency (LPLD) display during their whole life very high plasma TG levels often associated with episodes of postprandial abdominal pain, malaise, blurred vision, dizziness (hyperchylomicronemia syndrome) that may lead to recurrent pancreatitis episodes. Because of their very slow clearance in blood of their chylomicron-TG, these patients need to severely restrict their dietary fat intake to avoid these complications. Fortunately, novel treatments are being developed to circumvent LPL deficiency (LPLD) metabolic effect on chylomicron-TG clearance. However, there is no data on how LPLD affect organ-specific dietary fatty acid metabolism nor how the novel therapeutic agents may change this metabolism. For example, it is currently not understood how subjects with LPLD store their DFA into adipose tissues and whether they are able to use DFA as a fuel to sustain their cardiac metabolism, as healthy individuals do. This study aims to better understand theses two questions.

Who can join (things the study team will check)

✅ You may be able to join if…

• 8 healthy LPL-deficient individuals (LPLD subjects) with history of fasting TG > 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
• 8 control subjects (fasting glucose < 5.6, 2-hour post 75g OGTT glucose < 7.8 mmol/l and HbA1c < 5.8%; fasting TG < 1.5 mmol/l);
• age 18 to 75 yo;
• To be willing and able to adhere to the specifications of the protocol;
• To have signed an informed consent document indicating that they understood the purpose

🚫 You may not be able to join if…

• age < 18 yo;
• overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG
• Treatment with a fibrate, thiazolidinedione, beta-blocker or other drug known to affect lipid or carbohydrate metabolism (except statins, metformin, and other antihypertensive agents that can be safely interrupted);
• Treatment with anti-hypertensive medication (only for LPL-deficient individuals);
• presence of liver or renal disease; uncontrolled thyroid disorder;
• previous diagnosis of heparin-induced thrombocytopenia;
• Treatment with oral anticoagulation medication or platelet aggregation inhibiting drugs;
• A history of major hemorrhagic event;
• smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day;;
• Female of child-bearing potential who is pregnant, breast feeding or intends to become pregnant or pre-menopausal female with a positive serum pregnancy test at the time of enrollment.

Where this trial is running

• Centre de recherche du CHUS, Sherbrooke, Quebec, Canada

Who to contact

Frédérique Frisch · 819-346-1110- ext12394 · frederique.frisch@usherbrooke.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT04227678.