Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency
Postprandial Fatty Acid Metabolism in Subjects With Lipoprotein Lipase Deficiency
Sponsors
Source
Université de Sherbrooke
Oversight Info
Has Dmc
No
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
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 minutes.
Overall Status
Recruiting
Start Date
2019-12-09
Completion Date
2025-12-30
Primary Completion Date
2025-09-30
Phase
N/A
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Organ-specific Dietary Fatty Acid (DFA) partitioning |
2 months |
|
Myocardial DFA uptake |
2 months |
Secondary Outcome
Measure |
Time Frame |
|
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 |
|
Left ventricular function by Positron Emitting Positron (PET) ventriculography |
2 months |
|
Myocardial oxidative metabolism |
2 months |
|
Insulin sensitivity |
6 months |
|
Liver nonesterified fatty acids (NEFA) metabolism |
2 months |
|
Metabolites distribution in plasma |
2 months |
Enrollment
16
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
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
Arm Group Label
Control group-A1
LPLD group-A1
Intervention Type
Dietary Supplement
Intervention Name
Description
low fat meal: (500 mL, 898 Kcal, 13% fat, 20.3% protein and 62.3% carbohydrates) will be
ingested over 20 minutes
Arm Group Label
Control group- A0
Control group-A1
LPLD group-A0
LPLD group-A1
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
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.
Gender
All
Minimum Age
18 Years
Maximum Age
75 Years
Healthy Volunteers
Accepts Healthy Volunteers
Overall Official
Last Name |
Role |
Affiliation |
|
André Carpentier |
Principal Investigator |
Université de Sherbrooke |
Overall Contact
Last Name
Frédérique Frisch
Phone
819-346-1110- ext12394
frederique.frisch@usherbrooke.ca
Location
Facility |
Status |
Contact |
|
Centre de recherche du CHUS Sherbrooke 6146143 Quebec 6115047 J1H 5N4 Canada |
Recruiting |
Last Name: Frédérique Frisch Phone: 819-346-1110- ext12394 Email: frederique.frisch@usherbrooke.ca |
Location Countries
Country
Canada
Verification Date
2024-12-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Université de Sherbrooke
Investigator Full Name
André Carpentier
Investigator Title
tenured professor
Has Expanded Access
No
Condition Browse
Number Of Arms
4
Intervention Browse
Mesh Term
Heparin
Arm Group
Arm Group Label
Control group- A0
Arm Group Type
Other
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
Arm Group Label
LPLD group-A0
Arm Group Type
Other
Description
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
Arm Group Label
Control group-A1
Arm Group Type
Other
Description
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.
Arm Group Label
LPLD group-A1
Arm Group Type
Other
Description
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.
Firstreceived Results Date
N/A
Acronym
AGL12
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
Single (Outcomes Assessor)
Study First Submitted
January 7, 2020
Study First Submitted Qc
January 9, 2020
Study First Posted
January 14, 2020
Last Update Submitted
December 4, 2024
Last Update Submitted Qc
December 4, 2024
Last Update Posted
December 9, 2024
ClinicalTrials.gov processed this data on February 09, 2026
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.