Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

Brief Title

Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

Official Title

Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

Brief Summary

      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

Study Type


Primary Outcome

Organ-specific Dietary Fatty Acid (DFA) partitioning

Secondary Outcome

 Myocardial nonesterified fatty acids (NEFA) metabolism


Lipoprotein Lipase Deficiency



Study Arms / Comparison Groups

 Control group- A0
Description:  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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 9, 2019

Completion Date

December 30, 2022

Primary Completion Date

July 30, 2022

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

        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

          -  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




18 Years - 75 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


André Carpentier, 819-346-1110- ext12394, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Université de Sherbrooke


 Institut de Recherches Cliniques de Montreal

Study Sponsor

André Carpentier, Principal Investigator, Université de Sherbrooke

Verification Date

April 2021