The LD Lync Study - Natural History Study of Lipodystrophy Syndromes

Prospective Multicenter Natural History Study of Lipodystrophy Syndromes to Determine Prevalence, Incidence and Predictors of Diabetes and Severe Hypertriglyceridemia, and Their Complications

Genetic lipodystrophy syndromes are extremely rare, orphan diseases with overall estimated prevalence of less than 2,000 in the United States. These rare disorders characterized by selective loss of adipose tissue and predisposition to insulin resistance and its metabolic complications diabetes, dyslipidemia and hepatic steatosis. Due to these metabolic problems, atherosclerotic vascular disease, recurrent episodes of acute pancreatitis, cirrhosis and other morbidities complicate the lives of these patients.

In the last few years, several genes for CGL (AGPAT2, BSCL2, CAV1 and PTRF); FPL (LMNA, PPARG, AKT2, CIDEC, LIPE, PLIN1, PCYT1A and ADRA2A); MAD (LMNA and ZMPSTE24); APS (LMNA); autoinflammatory (PSMB8); NPS (FBN1, CAV1); SHORT syndrome (PIK3R1); and MDP syndrome (POLD1) have been identified. However, there is paucity of information about the natural history of these rare syndromes, especially genotype-specific causes of morbidity and mortality.

To overcome the problems outlined above, this multicenter, collaborative, prospective, observational natural history cohort study will be conducted on approximately 500 patients with genetic or acquired lipodystrophy syndromes. Patients will be assessed on a yearly basis for approximately 5 to 7 years to collect robust clinical, metabolic, morbidity and mortality data. Medical history and patient questionnaires will be completed on a yearly basis by patients registered in the study. Clinical data such as vitals, laboratory results and anthropometric measurements will also be collected from patients' medical records if available.

Study Overview

• Status: Recruiting
• Conditions: Lipodystrophy (Genetic or Acquired, Non HIV)

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Adam Neidert, M.S.; Phone Number: 734-615-0539; Email: aneidert@med.umich.edu
• Study Contact Backup: Name: Elif Oral, M.D.; Phone Number: 734-615-7271; Email: eliforal@med.umich.edu

Study Locations

• Turkey
  • İzmir, Turkey, 35380
    • Recruiting
    • Dokuz Eylul University
    • Contact: Baris Akinci, MD; Phone Number: 90 552 6001789; Email: barisakincimd@gmail.com
    • Contact: Merve Celik, MD; Phone Number: 90 537 5630430; Email: mdmervecelik@gmail.com
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health
      • Contact: Rebecca Brown, MD; Phone Number: 301-594-0609; Email: brownrebecca@niddk.nih.gov
      • Contact: Michelle Ashmus; Email: michelle.ashmus@nih.gov
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Recruiting
      • University of Michigan
      • Contact: Elif A Oral, MD; Phone Number: 734-615-7271; Email: eliforal@med.umich.edu
      • Contact: Adam H Neidert, MS; Phone Number: 734-615-0539; Email: aneidert@med.umich.edu
      • Principal Investigator: Elif A Oral, MD
      • Sub-Investigator: Nevin N Ajluni, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with a clinical diagnosis of genetic lipodystrophy

Description

Inclusion Criteria:

• Clinical diagnosis of genetic lipodystrophy Supportive data: 1) Presence of biallelic known disease-causing variants in the genes for autosomal recessive lipodystrophy syndromes; 2) Presence of a known (or de novo loss of function) disease-causing variant in the genes for autosomal dominant lipodystrophy syndromes.

Exclusion Criteria:

• HIV-infected patients with lipodystrophy
• Drug-induced lipodystrophy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of diabetes mellitus	Number of subjects with diabetes mellitus or who develop diabetes mellitus	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of severe hypertriglyceridemia	Number of subjects with severe hypertriglyceridemia (greater than 500 md/dL) or who develop severe hypertriglyceridemia	4 years
Incidence of severe morbidities and causes of mortality	Incidence of severe morbidities (acute pancreatitis, congestive heart failure, cirrhosis, liver failure) and causes of mortality in subjects	4 years

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Elif A Oral, MD, Professor of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Lipodystrophy
• Other Study ID Numbers: HUM00127427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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