Precision Diagnosis and Therapy for Rare Diseases by Interpreting Non-coding Genomes (PARADIGM)

Plain English Summary

Precision Diagnosis and Therapy for Rare Diseases by Interpreting Non-coding Genomes is a Not Applicable clinical trial sponsored by IRCCS Azienda Ospedaliero-Universitaria di Bologna studying Neuromuscular Diseases, Eye Diseases, Genetic Disease. This study aims to find the genetic causes of rare eye and neuromuscular diseases by looking at the non-coding parts of DNA. It's for patients and their families who have been diagnosed with or suspect they have rare eye or neuromuscular conditions, especially if previous genetic tests were unclear. Participation involves providing DNA samples and potentially undergoing genetic sequencing and analysis. Alternatives may include standard diagnostic genetic testing, but this study offers a deeper dive into less understood genetic regions. The trial aims to enroll 100 participants.

Official Summary

PARADIGM study, funded by the PNRR research grant, will focus on Eye Diseases (ED) and Neuro-Muscular Diseases (NMD) as groups of genetically heterogeneous diseases which are extensively studied by the Partners partecipating in the project; indeed ED and NMD are well clinically and molecularly characterized and approachable by drug-testing options already assessed and implemented by PARADIGM partners. ED and NMD represent good and compatible disease models as: * both are genetically heterogeneous disorders where missing heritability is likely to be hidden in non-coding variants; * many of the individual genes accountable for the ED and NMD cause autosomal recessive forms, increasing the chance of finding regulatory/splicing variants

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have a diagnosed rare eye or neuromuscular disease, or if your previous genetic tests were inconclusive. This includes cases where standard tests found no clear cause, or only a single gene change in a condition that usually requires two. The study also looks for specific types of genetic changes (like splicing or regulatory variants) in certain genes. You must provide informed consent, and for some family structures, a minimum number of affected family members are needed. This trial is studying Neuromuscular Diseases, Eye Diseases, Genetic Disease, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome of identifying genomic variants means the study aims to pinpoint the specific genetic changes responsible for a patient's rare disease within 22 months. The specific primary outcome measures are: Identification of genomic variants (22 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial is important because it addresses a gap in diagnosing rare genetic diseases by exploring the 'dark matter' of the genome, potentially leading to new diagnostic and therapeutic strategies. This research targets Neuromuscular Diseases, Eye Diseases, Genetic Disease, where improved treatment options are needed.

Investor Insight

This observational study focuses on a niche area of rare disease diagnostics, with potential for future therapeutic development, signaling a growing interest in precision medicine for underserved cond

Is This Trial Right for Me?

Ask your doctor if your condition might be caused by genetic factors not typically found in standard tests. Understand that participation involves genetic analysis, which may reveal the cause of your condition or identify new research avenues. Be prepared for potential follow-up discussions about the findings and their implications for treatment or family planning. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 100 participants

Interventions

• GENETIC: PARADIGM study aims to streamline the process from genomic characterization of RGD patients with ED/NMD to identification of the suitable personalized therapy. — Samples are collected by UO1/UO2/UO3. DNA/RNA samples are sent to UO3 for genome and transcriptome sequencing. In vitro systems or patient-derived cell models are used for in vitro experimental validation (UO2) or development of therapeutical approaches (UO2/UO4). Samples of cases still undiagnosed after the combined sequencing and validation approaches undergo long-read sequencing by an outsourcing facility. Sequencing data are transferred to UO1 for bioinformatic analysis and may be deposited

Primary Outcomes

• Identification of genomic variants (22 months)

Secondary Outcomes

• Evaluation of therapeutic efficiency (24 months)

Full Eligibility Criteria

Inclusion Criteria:

* patients/relatives of patients with clinical diagnosis of NMD/ED;
* patients/relatives of patients with inconclusive ES and aCGH data (no pathogenic/likely pathogenic variant) or finding of only a single hit (a pathogenic or likely pathogenic variant) in an autosomal recessive gene by ES (or aCGH) or no pathogenic or likely pathogenic variant but detection of a large region of genomic homozygosity surrounding a candidate gene;
* patients/relatives of patients with a finding of cryptic VUS (splicing/regulatory/noncoding CNVs) in ED/NMD genes or pathogenic cryptic variants in a selected number of representative cases.
* Signed informed consent to participate in the study.

Exclusion Criteria:

\- Trios or nuclear families where both unaffected parents do not consent to participate will be excluded (similarly, a minimum number of 3 affected family members will be needed in multigenerational pedigrees).

Trial Locations

• IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Frequently Asked Questions

Related Conditions

• Neuromuscular Diseases
• Eye Diseases
• Genetic Diseases
• Rare Diseases
• Undiagnosed Diseases
• Splicing Disorders
• Regulatory Gene Variants
• Genomic Heterogeneity
• Autosomal Recessive Disorders
• Personalized Medicine

More Neuromuscular Diseases Trials

View all Neuromuscular Diseases clinical trials