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Decoding the Genetic Landscape of Skeletal Diseases (SKDLAND)

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ClinicalTrials.gov Identifier: NCT05876416
Recruitment Status : Recruiting
First Posted : May 25, 2023
Last Update Posted : May 25, 2023
Sponsor:
Collaborators:
Karolinska University Hospital
Göteborg University
Information provided by (Responsible Party):
Giedre Grigelioniene, Karolinska Institutet

Tracking Information
First Submitted Date April 16, 2023
First Posted Date May 25, 2023
Last Update Posted Date May 25, 2023
Actual Study Start Date January 1, 2015
Estimated Primary Completion Date December 31, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 16, 2023)
  • New gene discoveries for genetic skeletal disorders (GSDs) [ Time Frame: 2023-2028 ]
    2-3 new disease causes and disease entities identified and reported per year for GSDs.
  • Improved knowledge regarding natural cause of rare GSDs [ Time Frame: 2023-2028 ]
    1-2 GSDs reported as small patient groups with the same condition and clinical characteristics/course.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: May 16, 2023)
  • Disease (GSD) associated traits and complications [ Time Frame: 2023-2028 ]
    The observations include internal malformations, metabolic, biochemical and growth parameters, and secondary complications.
  • Information on disease causing variants in GSD [ Time Frame: 2023-2028 ]
    During the study we identify several novel disease causing variants in known GSD genes and report them to databases.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Decoding the Genetic Landscape of Skeletal Diseases
Official Title Decoding the Genetic Landscape of Skeletal Diseases
Brief Summary This 5-year project aims to (1) search for genetic causes for yet unsolved congenital skeletal disorders (GSDs); (2) study consequences of the newly identified pathogenic variants in cells and in transgenic mice, (3) summarize data on natural course and complications for different GSD groups. For patients with unsolved GSD, the investigators search for molecular causes of GSDs using whole genome sequencing (WGS) and total ribonucleic acid (RNA) sequencing. Candidate gene variants are selected using genome or transcriptome sequencing data, clinical findings and screening of omics databases. Causality of the new variants is studied in cells and in transgenic mice models. Molecular and clinical findings are summarized for different GSD groups.
Detailed Description Genetic skeletal disorders (GSDs) are a large group of rare diseases caused by abnormalities in genes regulating skeletal development. This 5-year project aims to (1) search for genetic causes for yet unsolved congenital skeletal disorders; (2) study consequences of the newly identified pathogenic variants in cells and in transgenic mice, (3) summarize data on natural course and complications for different GSD groups. The project is a collaboration between the Dept of Clinical Genetics, Karolinska University Hospital, Lab of Clinical Genetics and Lab of Bone and Cartilage Physiology, Karolinska Institutet and Sahlgrenska Academy. In a well-characterized group of 300 GSD participants whose DNA samples were analyzed using whole genome sequencing (WGS), there are 120 study participants with unsolved diagnoses. For those participants, we search for molecular causes of GSDs using WGS and total RNA sequencing. Candidate gene variants are selected using genome or transcriptome sequencing data, clinical findings and screening of omics databases. Causality of the new variants is studied in cells and in transgenic mice models. Molecular and clinical findings are summarized for different GSD groups. Our results improve diagnostics for GSDs, advance knowledge on pathogenesis and help establishing new individual follow-up and treatment strategies for patients with GSDs. This project increases understanding of skeletal pathophysiology and will contribute to the development of novel treatment methods for skeletal diseases.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Genomic DNA samples, primary dermal fibroblasts, RNA from blood or fibroblasts
Sampling Method Non-Probability Sample
Study Population Individuals of any age with congenital skeletal diseases and their healthy relatives
Condition
  • Genetic Skeletal Diseases
  • Skeletal Dysplasia
  • Molecular Causes
  • Skeletal Disorder
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 16, 2023)		 450
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2026
Estimated Primary Completion Date December 31, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Clinically suspected skeletal dysplasia based on previous investigations

Abnormal height

Radiographic abnormalities of the skeleton in addition to other syndromic features

Healthy relatives of the affected study participants

Exclusion Criteria:

No radiographic data available from clinical investigations

Suspected environmental or multifactorial causes
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers Yes
Contacts
Contact: Giedre Grigelioniene, MD, PhD +46706287697 giedre.grigelioniene@ki.se
Contact: Hillevi Lindelöf, MD Hillevi.Lindelof@ki.se
Listed Location Countries Sweden
Removed Location Countries  
 
Administrative Information
NCT Number NCT05876416
Other Study ID Numbers 910715
2022-02647 ( Other Grant/Funding Number: Vetenskap Rådet/SRC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: Due to GDPR we are not able to share genomic data, but in case of joined reports anonymized clinical data such as growth parameters or information on malformations will be shared.
Current Responsible Party Giedre Grigelioniene, Karolinska Institutet
Original Responsible Party Same as current
Current Study Sponsor Karolinska Institutet
Original Study Sponsor Same as current
Collaborators
  • Karolinska University Hospital
  • Göteborg University
Investigators
Principal Investigator: Giedre Grigelioniene, MD, Dept Molecular Medicine and Surgery, KI
PRS Account Karolinska Institutet
Verification Date May 2023