AzTrials
AzTrials

Genetic DiseasesMENDELNCT02380729

Mutation Exploration in Non-acquired, Genetic Disorders and Its Impact on Health Economy and Life Quality

An observational study of Genetic Diseases, run by Charite University, Berlin, Germany at 3 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The MENDEL-study will investigate whether the use of gene panel or whole genome sequencing (WGS) will: 1. improve the rate of diagnosis and through this compare the performance of the two diagnostic approaches (gene panel vs. WGS), 2. Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Genetic Diseases
What is being tested?
Gene Panel Sequencing and Whole Genome Sequencing (WGS)
How many people
200 participants
Where
3 sitesGermany
Study dates
31 Jan 2015to 31 Dec 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Study population: Index patients: Children (age newborn to 18 years) who present with a suspected genetic disorder Parents: biological mother and father of each index case.

Who may be able to join

  • Diagnosis: Suspicion of genetic disease. (Only one of the following criteria is required.) [1.1] Family member(s) with similar phenotype OR [1.2] At least two affected organ systems OR [1.3] One affected organ system that is known to be associated with multiple disease causing genes (e.g. long QT syndrome) OR [1.4] Multiple birth defects
  • Both parents must be available for blood draw in order to confirm phase (segregation analysis) or in order to perform WGS of the trio at a later time point.
  • Age: from birth up until age 18 years
  • Gender: Both sexes will be included

Who cannot join

  • Suspicion that the phenotype is due to an acquired disease
  • Missing informed consent from both parents or from all legal guardians for genetic testing in the setting of a clinical trial.
  • Clinical diagnosis of a disease with a known monogenic cause, e.g. Phenylketonuria or Cystic fibrosis.

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

  • Department of General Pediatrics, Charité-Universitätsmedizin

    Berlin, 13353

  • Department of Neuropediatrics, Charité-Universitätsmedizin

    Berlin, 13353

  • Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin

    Berlin, 13353

Other trials in Germany

About this study

The MENDEL-study will investigate whether the use of gene panel or whole genome sequencing (WGS) will:

  1. improve the rate of diagnosis and through this compare the performance of the two diagnostic approaches (gene panel vs. WGS),
  2. investigate whether use of said sequencing approaches early in the diagnostic process results in reduced health care spending, and
  3. result in an improved quality of life for the patients and their parents.
Read the detailed description

Patients will be recruited from in- and outpatient clinics at the Otto Heubner Center, the Berlin Center for Rare Diseases, and the Institute for Medical Genetics and Human Genetics at Charité-Universitätsmedizin Berlin, Germany. Following informed consent, 5 ml EDTA blood will be obtained from the index case and 10 ml blood from each parent. Disease related phenotype information and the outcome of previous diagnostic tests and procedures will be recorded as part of Study visit #1.

[1] Study visit #1

  1. A medical genetics physical will be performed. Detailed clinical symptoms (phenotype) will be recorded using Human Phenotype Ontology (HPO) terminology.
  2. A detailed pedigree will be drawn.
  3. Age of disease onset will be determined.
  4. Results from previous diagnostic tests and procedures, as well as hospital stays, will be recorded.
  5. The parents will be asked to complete a validated, standardized quality of life questionnaire adapted for for rare disease. The questionnaire is available online or in paper form.

[2] Study visit #2a (optional)

This study visit will only take place in the event that gene panel sequencing identifies a variant of uncertain significance, where additional information would be needed in order to determine its pathogenicity (e.g. confirmational biochemical testing, collection of additional information). Relevant research findings will be discussed and the nature and necessity of the additional testing will be explained.

[3] Study visit #2b (optional)

This study visit will only take place in the event that WGS identifies a variant of uncertain significance where additional information is needed in order to determine its pathogenicity > see Study visit #2a.

[4] Study visit #3 (results session)

Results will be returned in the context of a genetic counseling session.

[5] Study visit #4 (6 months after Study visit #3)

The parents will be asked to complete the validated, standardized quality of life questionnaire adapted for rare disease again.

Being tested
Gene Panel Sequencing, Whole Genome Sequencing (WGS)
Keywords
Health care delivery, Human Phenotype Ontology, Mutation prioritization, Next Generation Sequencing, Mutation detection, Bioinformatic analysis, Quality of life
Medical subject headings
Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gene Panel SequencingGenetic

    Enrichment for and panel sequencing of 2942 disease genes listed in the Online Mendelian Inheritance of Man (OMIM) database.

  • Whole Genome Sequencing (WGS)Genetic

    Whole Genome Sequencing of the index case and of both parents in the event that Gene Panel Sequencing did not identify a disease-causing mutation.

Study groups in NCT02380729
Study groupRoleWhat they receive
Index patientsChildren between birth and 18 years of age manifesting with a suspected genetic disorder. Investigation: First Gene Panel Sequencing and if no mutation ist found > Whole Genome Sequencing (WGS)
Receives: Genetic: Gene Panel Sequencing; Genetic: Whole Genome Sequencing (WGS)
Parents of the index patientBoth parents of the index patient. Investigation: Whole Genome Sequencing (WGS) if no mutation is found by Gene Panel Sequencing of the index patient.
Receives: Genetic: Whole Genome Sequencing (WGS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Diagnostic yield through gene panel sequencing of 3089 known disease genes.

    The number of confirmed disease causing mutations that can be identified in 200 patients following gene panel sequencing and analysis with the PhenIX software.

    Measured: 6 months.

Secondary outcomes (3)

  1. Quality of Life

    Assessment of the parents' quality of life before and after molecular diagnostics and reception of a molecular genetic diagnosis.

    Measured: 2 years

  2. Manageability of a next generation sequencing (NGS) pipeline in routine clinical diagnostics

    Calculation of the duration [months] between recruitment of a family and the final genetic counselling.

    Measured: 2 years

  3. Health economy of NGS

    Comparison of the cost of "standard diagnostics" versus the use of gene panel sequencing or WGS at an early stage in the diagnostic process. Health economic analysis of the costs incurred for each patient through "the standard diagnostic approach" in comparison to costs incurred through the use of gene panel sequencing/WGS.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2015 (estimated)
  2. Study start31 Jan 2015
  3. Primary completion30 Jun 2017
  4. Study completion31 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Family based
Time perspective
Prospective
Enrolment
200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02380729
Sponsor's protocol ID
EA2_107_14
Acronym
MENDEL
Status last verified
Jan 2018
First submitted
18 Feb 2015
Last updated
26 Jan 2018
Results posted
No
Data monitoring committee
No

Publications

  • Zemojtel T, Kohler S, Mackenroth L, Jager M, Hecht J, Krawitz P, Graul-Neumann L, Doelken S, Ehmke N, Spielmann M, Oien NC, Schweiger MR, Kruger U, Frommer G, Fischer B, Kornak U, Flottmann R, Ardeshirdavani A, Moreau Y, Lewis SE, Haendel M, Smedley D, Horn D, Mundlos S, Robinson PN. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome. Sci Transl Med. 2014 Sep 3;6(252):252ra123. doi: 10.1126/scitranslmed.3009262.

    PubMed 25186178

Questions about this trial

What is this clinical trial studying?

An observational study of Genetic Diseases, run by Charite University, Berlin, Germany at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diagnostic yield through gene panel sequencing of 3089 known disease genes. (time frame: 6 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02380729, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in