Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Heparin, liquid meal.
- Who it may be relevant to
- Registry conditions: Lipoprotein Lipase Deficiency. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed description
The study protocol includes 3 visits: the screening visit and 2 postprandial metabolic studies performed in random order at an interval of 7 to 14 days, and performed with (A1) and without (A0) an intravenous (i.v.) heparin bolus followed by 250 IU/h i.v during 6 hours. Each metabolic study will last 9 hours (with 6 hours postprandial) and will include PET and stable isotopic tracer methods. At time 0, a low fat liquid meal will be ingested over 20 minutes.
Interventions
- Drug Heparin
an intravenous (i.v.) heparin bolus (50 IU/kg i.v.) followed by 250 IU/h i.v. during 6 hours, starting 15 minutes before ingestion of liquid meal - Dietary supplement liquid meal
low fat meal: (500 mL, 898 Kcal, 13% fat, 20.3% protein and 62.3% carbohydrates) will be ingested over 20 minutes
Primary outcome measures
- Organ-specific Dietary Fatty Acid (DFA) partitioning [Time frame: 2 months]
- Myocardial DFA uptake [Time frame: 2 months]
Secondary outcome measures (10)
- Myocardial nonesterified fatty acids (NEFA) metabolism [Time frame: 2 months]
- Dietary fatty acid oxidation rate [Time frame: 6 months]
- Total oxidation rate [Time frame: 2 months]
- postprandial plasma NEFA turnover [Time frame: 6 months]
- postprandial plasma glucose turnover [Time frame: 6 months]
- Left ventricular function by Positron Emitting Positron (PET) ventriculography [Time frame: 2 months]
- Myocardial oxidative metabolism [Time frame: 2 months]
- Insulin sensitivity [Time frame: 6 months]
- Liver nonesterified fatty acids (NEFA) metabolism [Time frame: 2 months]
- Metabolites distribution in plasma [Time frame: 2 months]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Single blind
- Primary purpose
- Basic science
Study locations
Canada · 1 center
- Centre de recherche du CHUS — Sherbrooke
Identifiers
NCT: NCT04227678 · 2019-2764