LCAT (Lecithin Cholesterol Acyl Transferase) Natural History Study (LCAT NHS)

LCAT Deficiency Disorders: Natural History and Identification of Biomarkers

The purpose of the LCAT (Lecithin cholesterol acyl transferase) Natural History Study (LCAT NHS) is to help identify people with a mutation in a gene called LCAT, collect and store information about their medical history and disease course, and to assess for associations and follow changes in clinical features and biomarkers of disease. This information will help health care providers better understand the natural history of disease of LCAT deficiency.

Study staff will collect information from previous clinical visits such as lab tests, physical exam findings, renal and cardiovascular imaging, findings from kidney biopsies and eye exams, and medication and other treatments. As part of this study the investigators are asking participants permission to reach out to their doctors to obtain medical records and stored samples (such as serum or plasma or biopsies) from past visits.

Participants may also be asked to join a web-based patient portal to complete a patient-outcomes survey.

As part of this study, participants will also be asked to do the following things at different times:

• Answer questions about:
• Demographic information (year of birth, age, gender, race/ethnicity, country)
• LCAT deficiency diagnosis such as year of diagnosis, type of diagnosis (clinical, genetic), genotype information/LCAT mutation status
• Medical history and family history and any updates
• A review of medications

If participants are able to come to a study visit in person the following may happen:

Physical examination including vital signs (height, weight, blood pressure, and heart rate) Urine and blood samples for laboratory testing. participants will be required to fast for 10 hours before the blood tests. A small blood sample may also be taken 2-4 hours after a meal.

• The following will be tested: the different types of cholesterol and other fats in the blood (lipids), standard hematology (type and number of blood cells), blood chemistries such as sodium, potassium, and calcium, thyroid function, liver panel (function of the liver), kidney function and the level of protein in urine
• Blood and urine samples may also be stored for future testing
• Genetic material will be collected
• Blood cells may be stored for future research
• Participants will have approximately 4.5 tablespoons of blood drawn annually.
• If not done previously, participants will complete an eye exam.
• Participants may be seen by a doctor specialized in renal disease

Study Overview

• Status: Recruiting
• Conditions: LCAT Deficiency
• Intervention / Treatment: Other: Demographics, diagnosis type, genotype, lipid profile, renal function profile, treatment allocation, ophthalmology exam, country of residence.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Marina Cuchel, MD, PhD; Phone Number: 2156627188; Email: mcuchel@pennmedicine.upenn.edu
• Study Contact Backup: Name: Gregory Alfaro; Phone Number: 2156622902; Email: greg.alfaro@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Marina Cuchel, MD, PhD
      • Contact: Gregory Alfaro; Phone Number: 215-662-2902; Email: greg.alfaro@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The registry aims to include data on any patients diagnosed with LCAT deficiency. This includes both patients that have been diagnosed on the basis of genetic analysis and patients that in the opinion of their physician meet the clinical criteria for a diagnosis of LCAT deficiency.

Description

Inclusion Criteria:

1. Males or Females of any age

2. Subjects with:

   1. a diagnosis of primary LCAT deficiency based on investigator assessment or laboratory results AND/OR
   2. a genetically confirmed mutation in the LCAT gene who are homozygous or compound heterozygous for LCAT loss-of-function mutations
3. Subjects or their legal guardian must be able to comprehend and be willing to provide a signed institutional review board/ethics committee (IRB/EC) approved Informed Consent Form. A waiver of consent will be requested for deceased patients, as determined by local regulatory requirements.

Exclusion Criteria:

1. Secondary causes of LCAT deficiency
2. Any other 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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaching 40 Patients	Outreach efforts will be made to reach a total of study 40 participants	Through study completion, an average of 4 years
Mean Age of Diagnosis	The investigators will determine the mean age of diagnosis of LCAT Deficiency	Through study completion, an average of 4 years
Average time to develop CKD (Chronic Kidney Disease)	The investigators will assess the average time it takes to develop chronic kidney disease	Through study completion, an average of 4 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Marina Cuchel, MD, PhD, University of Pennsylvania

Publications and helpful links

General Publications

• Vitali C, Bajaj A, Nguyen C, Schnall J, Chen J, Stylianou K, Rader DJ, Cuchel M. A systematic review of the natural history and biomarkers of primary lecithin:cholesterol acyltransferase deficiency. J Lipid Res. 2022 Mar;63(3):100169. doi: 10.1016/j.jlr.2022.100169. Epub 2022 Jan 20.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: January 4, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Renal Disease; LCAT Deficiency; Familial LCAT Deficiency; FLD (Familial LCAT Deficiency); Fish Eye Disease; FED (Fish Eye Disease); Lipoprotein X; LpX (Lipoprotein X)
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hypoalphalipoproteinemias; Hypolipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Cardiovascular Diseases; Kidney Diseases; Lecithin Cholesterol Acyltransferase Deficiency; Public Health; Environment and Public Health; Population Characteristics; Genetic Phenomena; Epidemiologic Measurements; Genotype; Demography
• Other Study ID Numbers: 833871

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