Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

Lipoprotein Lipase Deficiency Clinical Trial

— AGL12  

Official title:

Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04227678
• Other study ID #: 2019-2764
• Status: Recruiting
• Phase: N/A
• Start date: December 9, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: November 2023
• Source: Université de Sherbrooke
• Contact: Frédérique Frisch
• Phone: 819-346-1110- ext12394
• Email: frederique.frisch[@]usherbrooke.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: December 30, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperlipoproteinemia Type I
• Lipoprotein Lipase Deficiency

Intervention

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

Locations

Country	Name	City	State
Canada	Centre de recherche du CHUS	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Sherbrooke	Institut de Recherches Cliniques de Montreal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Myocardial DFA uptake	will be assessed using oral administration of [18F]-FTHA during dynamic PET acquisition.	2 months
Secondary	Myocardial nonesterified fatty acids (NEFA) metabolism	will be determined using [11C]-palmitate during dynamic PET acquisition.	2 months
Secondary	Dietary fatty acid oxidation rate	will be measured using breath [13C]-carbon dioxide enrichment	6 months
Secondary	Total oxidation rate	will be determined by indirect calorimetry	2 months
Secondary	postprandial plasma NEFA turnover	will be determined using stable isotope tracers of fatty acids	6 months
Secondary	postprandial plasma glucose turnover	will be determined using stable isotope tracers of glucose	6 months
Secondary	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
Secondary	Myocardial oxidative metabolism	will be determined using i.v. [11C]-acetate during dynamic PET/CT scanning.	2 months
Secondary	Insulin sensitivity	will be determined using a multiplex ELISA which will measure multiple analytes in a single experiment.	6 months
Secondary	Liver nonesterified fatty acids (NEFA) metabolism	will be determined using [11C]-palmitate during dynamic PET acquisition.	2 months
Secondary	Metabolites distribution in plasma	will be determined using oral administration of [18F]-FTHA	2 months