Healthy Clinical Trial
— ANTHEMOfficial title:
Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
This project aims to identify, through RNA-Seq technology, the genetic alterations underlying undiagnosed rare diseases in pediatric and adult patients with early onset and with negative WES. - Objective 1: Set up and validate techniques. Set-up and validation of the transcriptome analysis protocol in healthy subjects and in patients with known splicing alterations and/or altered RNA expression. - Objective 2: Diagnostic phase. Study of splicing alterations and RNA levels in cultured fibroblasts obtained from skin biopsies of patients with rare genetic diseases and negative exome. Exploratory goals - Compare the RNA expression profile obtained from skin biopsy-derived fibroblasts with the RNA expression profile from blood. The most relevant results will be validated in qRT-PCR. - To analyze the transcriptional and protein profile heterogeneity in skin-derived fibroblasts in enrolled subjects. To explore the effects of genetic (from WES) and transcriptional (from RNA-seq) alterations in participants' plasma and serum. Healthy controls Five healthy subjects will be recruited from the staff of the Mario Negri Institute for Pharmacological Research. The coded samples will be used to set up the method of isolation and culture of skin fibroblasts and RNA-Seq. Validation group For the set-up and validation of the skin fibroblast isolation and RNA-Seq procedure, ten adult patients with known diagnosis and with alterations in RNA levels and/or splicing will be recruited as positive controls. Patients who meet the requirements described above will be contacted by the doctors of the Daccò Center for an interview explaining the project. Those who agree to participate in the study will be asked to sign the informed consent before proceeding with the experimental part. "Discovery/Exploration" group The exploration cohort will be composed of 30 symptomatic undiagnosed patients with suspected genetic disease (children and adults with infantile onset) belonging to the Clinical Center of the Mario Negri Institute for Pharmacological Research and for whom WES investigations did not reveal causative genetic alterations.
Status | Recruiting |
Enrollment | 105 |
Est. completion date | September 2025 |
Est. primary completion date | September 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A and older |
Eligibility | Healthy subjects. Inclusion Criteria: - Male and female adults - Written informed consent Exclusion Criteria: - Inability to understand the potential risk and benefits of the study - Legal incapacity Validation cohort. Inclusion criteria: - Male and female adults - Genetic diseases affecting RNA levels (frameshifts, stop, large deletions, alteration of canonical splicing sites) - Written informed consent Exclusion criteria: - Underage patients - Inability to understand the potential risk and benefits of the study - Legal incapacity Discovery cohort. Inclusion criteria: - Male and female patients (children and adults with onset in infancy or early adulthood) with rare genetic undiagnosed diseases - Patients with no strong candidates based on previous genetic analysis such as WES, but with clinically suspicion of a genetic rare disease - Written informed consent Exclusion criteria: - Inability to understand the potential risk and benefits of the study - Legal incapacity |
Country | Name | City | State |
---|---|---|---|
Italy | Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò" | Ranica | BG |
Lead Sponsor | Collaborator |
---|---|
Mario Negri Institute for Pharmacological Research |
Italy,
Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, Haack TB, Graf E, Schwarzmayr T, Terrile C, Konarikova E, Repp B, Kastenmuller G, Adamski J, Lichtner P, Leonhardt C, Funalot B, Donati A, Tiranti V, Lombes A, Jardel C, Glaser D, Taylor RW, Ghezzi D, Mayr JA, Rotig A, Freisinger P, Distelmaier F, Strom TM, Meitinger T, Gagneur J, Prokisch H. Genetic diagnosis of Mendelian disorders via RNA sequencing. Nat Commun. 2017 Jun 12;8:15824. doi: 10.1038/ncomms15824. — View Citation
Lee H, Huang AY, Wang LK, Yoon AJ, Renteria G, Eskin A, Signer RH, Dorrani N, Nieves-Rodriguez S, Wan J, Douine ED, Woods JD, Dell'Angelica EC, Fogel BL, Martin MG, Butte MJ, Parker NH, Wang RT, Shieh PB, Wong DA, Gallant N, Singh KE, Tavyev Asher YJ, Sinsheimer JS, Krakow D, Loo SK, Allard P, Papp JC; Undiagnosed Diseases Network; Palmer CGS, Martinez-Agosto JA, Nelson SF. Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. Genet Med. 2020 Mar;22(3):490-499. doi: 10.1038/s41436-019-0672-1. Epub 2019 Oct 14. — View Citation
Yepez VA, Mertes C, Muller MF, Klaproth-Andrade D, Wachutka L, Fresard L, Gusic M, Scheller IF, Goldberg PF, Prokisch H, Gagneur J. Detection of aberrant gene expression events in RNA sequencing data. Nat Protoc. 2021 Feb;16(2):1276-1296. doi: 10.1038/s41596-020-00462-5. Epub 2021 Jan 18. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Set up and validate the transcriptome analysis procedure in healthy controls and in patients diagnosed with known genetic diseases and with known splice/expression altering variants | WES analyses for DNA isolation | At day 0 | |
Primary | Analyse alterations of mRNA levels and splicing in cultured fibroblasts derived from patients with rare diseases and an inconclusive WES. To investigate the heterogeneity of the transcriptomic and proteomic profile | Skin-derived fibroblasts | At day 0 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06052553 -
A Study of TopSpin360 Training Device
|
N/A | |
Completed |
NCT05511077 -
Biomarkers of Oat Product Intake: The BiOAT Marker Study
|
N/A | |
Recruiting |
NCT04632485 -
Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
|
||
Completed |
NCT05931237 -
Cranberry Flavan-3-ols Consumption and Gut Microbiota in Healthy Adults
|
N/A | |
Completed |
NCT04527718 -
Study of the Safety, Tolerability and Pharmacokinetics of 611 in Adult Healthy Volunteers
|
Phase 1 | |
Terminated |
NCT04556032 -
Effects of Ergothioneine on Cognition, Mood, and Sleep in Healthy Adult Men and Women
|
N/A | |
Completed |
NCT04998695 -
Health Effects of Consuming Olive Pomace Oil
|
N/A | |
Completed |
NCT04065295 -
A Study to Test How Well Healthy Men Tolerate Different Doses of BI 1356225
|
Phase 1 | |
Completed |
NCT04107441 -
AX-8 Drug Safety, Tolerability and Plasma Levels in Healthy Subjects
|
Phase 1 | |
Completed |
NCT01442831 -
Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C] TR 701 In Healthy Adult Male Subjects
|
Phase 1 | |
Terminated |
NCT05934942 -
A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood
|
Phase 1 | |
Recruiting |
NCT05525845 -
Studying the Hedonic and Homeostatic Regulation of Food Intake Using Functional MRI
|
N/A | |
Completed |
NCT05515328 -
A Study in Healthy Men to Test How BI 685509 is Processed in the Body
|
Phase 1 | |
Completed |
NCT05030857 -
Drug-drug Interaction and Food-effect Study With GLPG4716 and Midazolam in Healthy Subjects
|
Phase 1 | |
Completed |
NCT04967157 -
Cognitive Effects of Citicoline on Attention in Healthy Men and Women
|
N/A | |
Recruiting |
NCT04714294 -
Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of HPP737 in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT04494269 -
A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls
|
Phase 1 | |
Completed |
NCT04539756 -
Writing Activities and Emotions
|
N/A | |
Recruiting |
NCT04098510 -
Concentration of MitoQ in Human Skeletal Muscle
|
N/A | |
Completed |
NCT03308110 -
Bioavailability and Food Effect Study of Two Formulations of PF-06650833
|
Phase 1 |