Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Organ-specific Dietary Fatty Acid (DFA) partitioning
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Control group- A0
Control group: Healthy subjects with fasting glucose < 5.6, 2-hour post 75g Oral Glucose Tolerance Test (OGTT) glucose < 7.8 mmol/l and HbA1c < 5.8%; fasting TG < 1.5 mmol/l);
A0: without heparin administered
干预措施: liquid meal (Dietary Supplement)
LPLD group-A0
LPLD group: LPL deficient subjects with history of fasting TG > 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
A0: without heparin administered
干预措施: liquid meal (Dietary Supplement)
Control group-A1
Control group: Healthy subjects with fasting glucose < 5.6, 2-hour post 75g OGTT glucose < 7.8 mmol/l and HbA1c < 5.8%; fasting TG < 1.5 mmol/l);
A1: with 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.
干预措施: Heparin (Drug)
Control group-A1
Control group: Healthy subjects with fasting glucose < 5.6, 2-hour post 75g OGTT glucose < 7.8 mmol/l and HbA1c < 5.8%; fasting TG < 1.5 mmol/l);
A1: with 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.
干预措施: liquid meal (Dietary Supplement)
LPLD group-A1
LPLD group: LPL deficient subjects with history of fasting TG > 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
A1: with 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.
干预措施: Heparin (Drug)
LPLD group-A1
LPLD group: LPL deficient subjects with history of fasting TG > 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
A1: with 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.
干预措施: liquid meal (Dietary Supplement)
结局指标
主要结局
Organ-specific Dietary Fatty Acid (DFA) partitioning
时间窗: 2 months
will be determined using oral administration of \[18F \]-Fluoro-6-Thia- Heptadecanoic Acid (FTHA ) during whole-body acquisition.
Myocardial DFA uptake
时间窗: 2 months
will be assessed using oral administration of \[18F\]-FTHA during dynamic PET acquisition.
次要结局
- postprandial plasma glucose turnover(6 months)
- Myocardial oxidative metabolism(2 months)
- Insulin sensitivity(6 months)
- Myocardial nonesterified fatty acids (NEFA) metabolism(2 months)
- Total oxidation rate(2 months)
- Left ventricular function by Positron Emitting Positron (PET) ventriculography(2 months)
- Liver nonesterified fatty acids (NEFA) metabolism(2 months)
- Metabolites distribution in plasma(2 months)
- Dietary fatty acid oxidation rate(6 months)
- postprandial plasma NEFA turnover(6 months)
研究者
André Carpentier
tenured professor
Université de Sherbrooke