Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

NCT04227678 | Recruiting

• 1 other identifier: 2019-2764
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Lipoprotein Lipase Deficiency

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Myocardial nonesterified fatty acids (NEFA) metabolism

  2 months

• Dietary fatty acid oxidation rate

  6 months

• Total oxidation rate

  2 months

• postprandial plasma NEFA turnover

  6 months

• postprandial plasma glucose turnover

  6 months

Study Arms (4)

Control group- A0

OTHER

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

LPLD group-A0

OTHER

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

Control group-A1

OTHER

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.

Drug: Heparin; Dietary Supplement: liquid meal

LPLD group-A1

OTHER

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.

Drug: Heparin; Dietary Supplement: liquid meal

Interventions

Heparin DRUG

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

Control group-A1; LPLD group-A1

liquid meal DIETARY_SUPPLEMENT

low fat meal: (500 mL, 898 Kcal, 13% fat, 20.3% protein and 62.3% carbohydrates) will be ingested over 20 minutes

Control group- A0; Control group-A1; LPLD group-A0; LPLD group-A1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy LPL-deficient individuals (LPLD subjects) with history of fasting TG \> 5 mmol/l and homozygote or compound heterozygote for a LPL-gene mutation;
• 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 qualify 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.

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Institut de Recherches Cliniques de Montreal: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

MeSH Terms

Conditions

Hyperlipoproteinemia Type I

Interventions

Heparin

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• André Carpentier

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédérique Frisch

CONTACT

819-346-1110- ext12394; frederique.frisch@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: tenured professor

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: January 14, 2020
• Study Start: December 9, 2019
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

CA (1)