Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency (AGL12)

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.

Study Overview

• Status: Recruiting
• Conditions: Lipoprotein Lipase Deficiency
• Intervention / Treatment: Dietary supplement: liquid meal; Drug: Heparin

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Frédérique Frisch; Phone Number: 819-346-1110- ext12394; Email: frederique.frisch@usherbrooke.ca

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Recruiting
      • Centre de Recherche du CHUS
      • Contact: Frédérique Frisch; Phone Number: 819-346-1110- ext12394; Email: frederique.frisch@usherbrooke.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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	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
Other: 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	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
Other: 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.	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; 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
Other: 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.	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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ-specific Dietary Fatty Acid (DFA) partitioning	will be determined using oral administration of [18F ]-Fluoro-6-Thia- Heptadecanoic Acid (FTHA ) during whole-body acquisition.	2 months
Myocardial DFA uptake	will be assessed using oral administration of [18F]-FTHA during dynamic PET acquisition.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial nonesterified fatty acids (NEFA) metabolism	will be determined using [11C]-palmitate during dynamic PET acquisition.	2 months
Dietary fatty acid oxidation rate	will be measured using breath [13C]-carbon dioxide enrichment	6 months
Total oxidation rate	will be determined by indirect calorimetry	2 months
postprandial plasma NEFA turnover	will be determined using stable isotope tracers of fatty acids	6 months
postprandial plasma glucose turnover	will be determined using stable isotope tracers of glucose	6 months
Left ventricular function by Positron Emitting Positron (PET) ventriculography	will be determined using [11C]-acetate PET/CT. 180 megabecquerel (MBq) will be administered by bolus injection	2 months
Myocardial oxidative metabolism	will be determined using i.v. [11C]-acetate during dynamic PET/CT scanning.	2 months
Insulin sensitivity	will be determined using a multiplex ELISA which will measure multiple analytes in a single experiment.	6 months
Liver nonesterified fatty acids (NEFA) metabolism	will be determined using [11C]-palmitate during dynamic PET acquisition.	2 months
Metabolites distribution in plasma	will be determined using oral administration of [18F]-FTHA	2 months

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Collaborators: Institut de Recherches Cliniques de Montreal
• Investigators: Principal Investigator: André Carpentier, Université de Sherbrooke

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type I; Carbohydrates; Glycosaminoglycans; Polysaccharides; Heparin
• Other Study ID Numbers: 2019-2764

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No