HoFH, the International Clinical Collaborators Registry (HICC)

HoFH, the International Clinical Collaborators - A Global HoFH Data-sharing Platform

Homozygous familial hypercholesterolemia (HoFH), a rare inherited disorder caused by bi-allelic mutations in the LDL Receptor pathway, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth and premature atherosclerotic cardiovascular disease (ASCVD). Our current knowledge about HoFH is disjointed and largely stems from relatively small case series and expert opinion. HICC (Homozygous FH International Clinical Collaborators) is a global consortium of clinicians who are contributing de-identified data of patients diagnosed with HoFH with the goal to advance our understanding of this rare disease.

Study Overview

• Status: Recruiting
• Conditions: Homozygous Familial Hypercholesterolemia
• Intervention / Treatment: Other: Demographics, diagnosis type, genotype, lipid profile, treatment allocation, country of residence.

Detailed Description

The HICC registry is an observational, multicenter, international registry collecting de-identified clinical and genetic information from patients with homozygous Familial Hypercholesterolemia (HoFH) worldwide.

Patients are eligible to be enrolled in the registry based on the diagnosis of HoFH by the treating clinician, irrespective of how the diagnosis was made. To generate up-to-date data reflecting current rather than historic practice, patients who died or were lost to follow-up prior to 2010 are excluded.

Anonymized data on demographics, type of HoFH diagnosis (clinical and/or based on the results of a genetic test), genetic results, (cardiovascular) medical history, relevant family history, physical examination, laboratory measurements, lipid lowering treatment and cardiovascular imaging are collected for 3 different time points: at diagnosis, at enrolment and at time of best lipid profile (if this is different from time at enrolment). Data are collected using pre-definite electronic case report forms to ensure uniformity of data collected. Primary analysis will be cross-sectional (e.g. based on country of residence, age, etc)

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Marina Cuchel, MD, PhD; Phone Number: 2156627188; Email: mcuchel@pennmedicine.upenn.edu
• Study Contact Backup: Name: Lauren Vincent, MRA; Phone Number: 2156155448; Email: laurv@pennmedicine.upenn.edu

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Department of Vascular Medicine, Amsterdam UMC
    • Contact: G. Kees Hovingh, MD, PhD; Email: g.k.hovingh@amsterdamumc.nl
    • Principal Investigator: G. Kees Hovingh, MD, PhD
• South Africa
  • Cape Town, South Africa
    • Recruiting
    • Department of Medicine, Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, University of Cape Town
    • Contact: Dirk J Blom; Email: dirk.blom@uct.ac.za
    • Principal Investigator: Dirk J Blom
  • Johannesburg, South Africa
    • Recruiting
    • c. Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of Witwatersrand
    • Contact: Frederick J Raal; Email: frederick.raal@wits.ac.za
    • Principal Investigator: Frederick J Raal, PhD
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Lauren Vincent, MRA; Phone Number: 2156155448; Email: laurv@pennmedicine.upenn.edu
      • Contact: Marina Cuchel, MD, PhD; Phone Number: 215-662-7188; Email: mcuchel@pennmedicine.upenn.edu
      • Principal Investigator: Marina Cuchel, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The registry aims to include data from as many patients diagnosed with HoFH as possible. All patients must be living at time of entry into the database or have been deceased within the last 5 years.

Description

Inclusion Criteria:

• Diagnosis of homozygous familial hypercholesterolemia (HoFH) clinically of genetically determined

Exclusion Criteria:

• No diagnosis of HoFH

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HoFH; Patients diagnosed with HoFH by their physicians, either based on clinical or genetic criteria.	Other: Demographics, diagnosis type, genotype, lipid profile, treatment allocation, country of residence.; Differences in diagnosis, genotype, lipid profile treatment allocation among HoFH patients worldwide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants entered into the database	Number of study participants with homozygous familial hypercholesterolemia	Through study completion, an average of 8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Untreated and treated LDL-C levels across world income regions	Number of treated versus number of untreated subjects with relevant LDL-C levels	Through study completion, an average of 8 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: University of Amsterdam; University of Cape Town; University of Witwatersrand, South Africa
• Investigators: Principal Investigator: Marina Cuchel, MD, PhD, University of Pennsylvania

Publications and helpful links

General Publications

• Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel M; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators. Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet. 2022 Feb 19;399(10326):719-728. doi: 10.1016/S0140-6736(21)02001-8. Epub 2022 Jan 28.
• Mulder JWCM, Schonck WAM, Tromp TR, Reijman MD, Reeskamp LF, Hovingh GK, Blom DJ, Roeters van Lennep JE. Real-world family planning and pregnancy practices in women with homozygous familial hypercholesterolemia. Atherosclerosis. 2025 May;404:119187. doi: 10.1016/j.atherosclerosis.2025.119187. Epub 2025 Apr 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 4, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; Registry; Homozygous Familial Hypercholesterolemia; Autosomal Dominant; Autosomal Recessive Hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia; Hyperlipoproteinemia Type III; Multiple Pterygium Syndrome, Autosomal Dominant; Public Health; Environment and Public Health; Population Characteristics; Genetic Phenomena; Epidemiologic Measurements; Genotype; Demography
• Other Study ID Numbers: HICC

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