Physiological Effects of ANGPTL3 Variants in Humans

To evaluate the role of ANGPTL3, on lipid metabolism. To explore the role of this protein on glucose metabolism.

Study Overview

• Status: Recruiting
• Conditions: Hypocholesterolemia
• Intervention / Treatment: Other: Kinetics test, oral fat tolerance test, and an oral glucose tolerance test.

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marina Cuchel, MD, PhD; Phone Number: 215-662-7188; Email: mcuchel@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Marina Cuchel, MD, PhD
      • Contact: Lauren Vincent, MRA; Phone Number: 215-615-5448

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects aged 18 or older meeting at least one of the following criteria

  1. Carrying genetic variants in the gene encoding for ANGPTL3,
  2. Unaffected controls matched for age, race, gender,
  3. Willing to follow study procedures

  4. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Marina Cuchel, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Lipid Metabolism; Angiopoietin-like protein 3 deficiency
• Other Study ID Numbers: 833684; R01HL148769 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No