Clinical and Molecular Biomarker Studies in RAI1 (Retinoic Acid-Induced 1) -Related Disorders

NCT06274164 | Recruiting

• 1 other identifier: H-54820 / RAI1
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, there is no clinically available genetic-based treatment for RAI1 (Retinoic Acid-Induced 1) -related disorders other than symptomatic management and there are no established clinical or molecular biomarkers that could be used as measures for the efficacy of therapy in future treatment studies. Biomarkers are measures of what is happening inside the body, shown by the results of laboratory, imaging or other tests. Biomarkers can help doctors and scientists diagnose diseases and health conditions, monitor responses to treatment and see how a person's disease or health condition changes over time. The goal of this observational and laboratory study is to develop clinical, neurophysiology and molecular biomarkers in RAI1-related disorders. The main question\[s\] it aims to answer are:

• to characterize the disease features more precisely and analyze the differentiating and overlapping features of RAI1-related disorders (Smith-Magenis syndrome and Potocki-Lupski Syndrome)
• to identify clinical, neurophysiology, and laboratory biomarkers that differentiate RAI1-related disorders one from another. Participants will have to complete:
• a clinical examination
• a blood draw
• a skin biopsy (optional)
• a sleep study Researchers will compare patients' blood to control group's blood for biomarker studies.

Conditions

RAI1 Gene 17P11.2 Deletion+Duplication

Keywords

Smith-Magenis syndrome (SMS); Potocki-Lupski Syndrome (PTLS); RAI1-related disorders; Retinoic Acid-Induced 1-related disorders

Outcome Measures

Primary Outcomes (3)

• Rate of neurological clinical finding

  Identify biomarkers which have suitable stability for use in clinical settings by combining quantitative comparisons from the visit with qualitative literature/retrospective chart review synthesis, to prioritize measures for inclusion in a panel of candidate biomarkers. Investigators expect to find a clinical exam finding such as tremor which can be measurable objectively or behavior which can be relied on caregiver's report.

  2029

• Rate of electroencephalogram (EEG) and/or sleep abnormalities

  Identify biomarkers which have suitable stability for use in clinical settings by combining quantitative comparisons from the visit with qualitative literature/retrospective chart review synthesis, to prioritize measures for inclusion in a panel of candidate biomarkers. To identify candidate oscillatory circuitry biomarkers of Smith-Magenis syndrome (SMS) and Potocki-Lupski Syndrome (PTLS), investigators will use EEG and sleep metrics.

  2029

• Concentration of downstream molecular pathway interactors of RAI1

  Identify biomarkers which have suitable stability for use in clinical settings by combining quantitative comparisons from the visit with qualitative literature synthesis, to prioritize measures for inclusion in a panel of candidate biomarkers. There are no biomarkers that trace disease stage and severity in RAI1-related disorders. Towards this goal, investigators aimed to identify molecular biomarkers from patients' plasma by quantifying metabolites.

  2029

Study Arms (2)

Patient group

Subject enrollment: patients with RAI1-related disorders will be enrolled and will complete the following assessments: * Clinical studies: vitals, history and physical examinations. * Neurophysiological studies: sleep/EEG study (for a selected patient population). * Molecular (biomarkers) studies: blood (required) and skin biopsy (optional).

Diagnostic Test: Electroencephalography/Polysomnography (EEG/PSG); Procedure: Skin Biopsy; Diagnostic Test: Blood draw

Control group

Subject enrollment: healthy family members of the patients with RAI1-related disorders who are willing to give a blood sample. Molecular (biomarkers) studies: blood samples will be used as healthy control for biomarker studies.

Diagnostic Test: Blood draw

Interventions

Electroencephalography/Polysomnography (EEG/PSG) DIAGNOSTIC_TEST

Instigators will determine if subjects are candidate for the procedure. A sleep study records the brain electrical waves, the oxygen level in the blood, heart rate breathing, as well as eye and leg movements. Subjects will need to be admitted overnight for the sleep study.

Also known as: sleep study

Patient group

Skin Biopsy PROCEDURE

A special 3-4 mm (0.12 inches) wide circular tool will be used to remove a small section of skin including deeper layers. A numbing cream or injectable anesthetic (i.e. lidocaine) will be applied to the area before the procedure. Sample will be used to create a cell line. This means that investigators would treat the cells from the sample in a way that allows to grow them in the laboratory. Investigators will then use these cells in research.

Patient group

Blood draw DIAGNOSTIC_TEST

A single blood sample of 15 cc (not exceeding 3 cc per kg) (\~3 teaspoons) will be collected for metabolomics (biomarker) study. From available family members, same amount of blood will be obtained to use as a control sample.

Control group; Patient group

Eligibility Criteria

• Age: 1 Month - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with RAI1-related disorders who are willing to participate in clinical, neurophysiological and molecular studies, will be enrolled, as well as healthy family controls. Subjects will have to travel to Texas Children's Hospital to complete study activities.

You may qualify if:

• Patient group:
• Patients who have RAI1-related disorder confirmed by genetic testing including karyotyping, fluorescence in situ hybridization (FISH), array Comparative Genomic Hybridization (aCGH), single nucleotide polymorphism (SNP) array and next generation sequencing performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
• Grossly intact hearing and vision as per parent report
• Age between 1 month to 60 years old
• Able to complete the study (i.e., travel to site and spend 1 day in Houston)
• Caregiver with spoken and written English at a level adequate to give informed assent (consent on behalf of the patient) for participation.
• Control group:
• Healthy family member, not having a RA1-related disorder
• Age between 5 years to 80 years old

You may not qualify if:

• Patient group:
• Contraindication for blood draw or skin biopsy as determined by the enrolling provider (e.g., bleeding diathesis)
• Patients who are at high risk including ventilator/tracheostomy dependent, poorly controlled endocrine disorders, and unstable seizures (will be assessed by neurologist), end-stage renal disease.
• Participation in any investigational treatment study
• Control group:
• Patients who have RAI1-related disorder confirmed by genetic testing.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Optional Skin biopsy will performed and used to generate cell lines.

MeSH Terms

Conditions

Smith-Magenis Syndrome; Potocki-Lupski syndrome

Interventions

Electroencephalography; Polysomnography; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Chronobiology Disorders; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Monitoring, Physiologic; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Davut Pehlivan, MD

  Texas Children's Hospital - Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Davut Pehlivan, MD

CONTACT

(713) 798-6970; pehlivan@bcm.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Assistant Professor, Pediatrics-Neurology

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: February 23, 2024
• Study Start: March 13, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)