Physiological Effects of ANGPTL3 Variants in Humans

Study Overview
=================
Brief Summary
-----------------
To evaluate the role of ANGPTL3, on lipid metabolism. To explore the role of this protein on glucose metabolism.

Detailed Description
-----------------
Oral fast tolerance test, lipoprotein kinetics and a glucose tolerance test to evaluate the role of ANGPTL3, on lipid metabolism and to explore the role of this protein on glucose metabolism.

Official Title
-----------------
Physiological Effects of ANGPTL3 Variants in Humans

Conditions
-----------------
Hypocholesterolemia

Intervention / Treatment
-----------------
* Other: Kinetics test, oral fat tolerance test, and an oral glucose tolerance test.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects aged 18 or older meeting at least one of the following criteria Carrying genetic variants in the gene encoding for ANGPTL3, Unaffected controls matched for age, race, gender, Willing to follow study procedures Able to provide inform consent Exclusion Criteria: Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study, or confound the study data Taking any medication that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study, or confound the study data Women that are pregnant or nursing History of liver disease or abnormal liver function tests (>2x upper limit of normal) History of kidney disease or chronic renal insufficiency (eGFR <60 mL/min/1.73 m2) Uncontrolled hypertension (>160/100 mmHg) Uncontrolled diabetes Anemia (hemoglobin <11.0 mg/dL) History of a non-skin malignancy within the previous 5 years Major surgery within the past 3 months History of any organ transplant History of alcohol or drug abuse Participation in clinical trials assessing the efficacy and safety of drugs affecting lipid metabolism within the past 6 weeks (or longer depending on the known half-life of the drug) that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study, or confound the study data Inability to comply to study procedures

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Variant<br>Volunteers with known ANGPTL3 variants | Other: Kinetics test, oral fat tolerance test, and an oral glucose tolerance test.<br>* Subjects will participate in a kinetics test, oral fat tolerance test, and an oral glucose tolerance test.<br>|
| Other: Non-variant<br>Healthy volunteers with no ANGPTL3 variants | Other: Kinetics test, oral fat tolerance test, and an oral glucose tolerance test.<br>* Subjects will participate in a kinetics test, oral fat tolerance test, and an oral glucose tolerance test.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The role of ANGPTL3 on lipid metabolism. | Assessing ApoB-containing lipoprotein fractional catabolic rate | through study completion, an average of 13 weeks | 
| The role of this protein on glucose metabolism. | Looking for glucose area under the curve following Oral Glucose Tolerance Test | through study completion, an average of 13 weeks | 
| The role of ANPTL3 on fatty acids | Looking for fatty acids area under the curve following Oral Fat Tolerance Test | through study completion, an average of 13 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Angiopoietin-like protein 3 deficiency, Lipid Metabolism