Cystinosis Clinical Trial
— GENESISOfficial title:
Scientific Basis for a Newborn Screening for Cystinosis and Primary Hyperoxaluria
In Germany parents of newborns are offered newborn screening (NBS) for 17 congenital diseases as a standard benefit of statutory health insurance. NBS in Germany is voluntary. Cystinosis and hyperoxaluria are very rare diseases. They are inherited autosomal-recessively. Neither disease can be detected by the methods established in routine NBS. However, common genetic mutations are known for both diseases. The aim of the study is to provide a scientific basis for molecular genetic NBS for cystinosis and primary hyperoxaluria (PH). Specifically, the study will investigate whether the inclusion of these diseases into general NBS should be recommended. By observing the identified infants in comparison to patients symptomatically diagnosed outside of the pilot project, it will be determined whether and to what extent early diagnosis and therapy lead to a more favorable prognosis. The screening laboratory Hannover, Germany is involved in the project. Hospitals that send their dry blood spot cards for routine NBS to Hannover are offered participation in the project. Parents who want to participate receive an additional information sheet. A parent and the attending physician sign the information sheet as documentation of informed consent, which allows data transfer and patient referral to a specialist in case of a positive result. Molecular genetic screening in the pilot project is performed from the same dry blood spot card used for routine NBS. In both diseases, testing is performed for 2 known mutations: In cystinosis for the 2 mutations most common in Germany, and in PH for the most common mutation in infantile hyperoxaluria (PH1) and in Europe (PH3). Normal findings are not communicated to the parents, which may contact the laboratory to ask for them. Parents of newborns with two mutations in the cystinosis gene are immediately informed about the disease by a physician. Further diagnostics to confirm the disease are organized close to home. In contrast, parents of newborns with only one mutation in one of the two hyperoxaluria genes are informed. They are asked to send spot urines of the newborn to the hyperoxaluria center. Only if these are abnormal, further evaluation will be performed. The study started on 15.03.2022. The aim is to screen 200,000 newborns until 2025. If the benefit of early diagnosis and therapy can be shown, an application for inclusion of a NBS for these two diseases in the routine NBS program will be submitted to the German government.
Status | Recruiting |
Enrollment | 200000 |
Est. completion date | June 30, 2026 |
Est. primary completion date | December 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 32 Hours to 72 Hours |
Eligibility | Inclusion Criteria: - Newborns participating at the NGS with parent's consent to participate in this screening project Exclusion Criteria: - Newborns without parent's consent to participate in this screening project. |
Country | Name | City | State |
---|---|---|---|
Germany | Screening Laboratory Hanover | Hanover | Lower Saxony |
Lead Sponsor | Collaborator |
---|---|
Cystinose Stiftung | Medical Genetics Mainz, Pediatry Kastanienhof Koeln, Screening Laboratory Hannover, University Hospital Cologne |
Germany,
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Hohenfellner K, Niessl C, Haffner D, Oh J, Okorn C, Palm K, Schlingmann KP, Wygoda S, Gahl WA. Beneficial effects of starting oral cysteamine treatment in the first 2 months of life on glomerular and tubular kidney function in infantile nephropathic cystinosis. Mol Genet Metab. 2022 Aug;136(4):282-288. doi: 10.1016/j.ymgme.2022.06.009. Epub 2022 Jul 1. — View Citation
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Hoppe B, Koch A, Cochat P, Garrelfs SF, Baum MA, Groothoff JW, Lipkin G, Coenen M, Schalk G, Amrite A, McDougall D, Barrios K, Langman CB. Safety, pharmacodynamics, and exposure-response modeling results from a first-in-human phase 1 study of nedosiran (PHYOX1) in primary hyperoxaluria. Kidney Int. 2022 Mar;101(3):626-634. doi: 10.1016/j.kint.2021.08.015. Epub 2021 Sep 2. — View Citation
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Both diseases | For both diseases the time interval will be evaluated from the time of identification in screening to the introduction of therapy. | time interval until start of treatment | |
Primary | Newborns with confirmed diagnosis of Cystinosis | Newborns identified with 57-kb CTNS mutation homozygous, compound heterozygous, with c.18_21delGACT p.T7Ffs*7 homozygous or compound heterozygous and elevated white blood cell cystine level. | 12 months | |
Primary | Number of newborns with heterozygous mutations | Newborns identified with heterozygous CTNS mutations of 57-kb CTNS and heterozygous c.18_21delGACT p.T7Ffs*7 mutations | 12 months | |
Primary | Patients with PH1 and PH3 | Newborns identified with heterozygous PH1 c.508G>A and PH3, C700+5G>T and further positive evaluation of urine and genetic analysis. | 12 months | |
Secondary | Newborns identified with heterozygous PH1 c.508G>A and PH3, C700+5G>T | Results of urine analysis of patients with heterozygous PH1 c.508G>A and PH3, C700+5G>T | 12 months |
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