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

NCT ID: NCT06274164

Last Updated: 2025-05-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

90 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-03-13

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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20 SMS (Smith-Magenis syndrome) patients and 20 PTLS (Potocki-Lupski Syndrome) patients will be enrolled in the study. Additionally, up to 50 healthy controls will be enrolled among family members of patients.

All the assessments may be completed during a one-time visit at the hospital which includes an overnight stay for the sleep study for selected individuals. In case all the procedures could not be completed during the one-time visit, subjects may be asked to come again for the remaining procedure.

Tests, procedures and samples to be completed or collected:

* Demographics will be collected
* History and physical examination: A detailed birth, medical, surgical and medication history will be collected as well as seizure and movement disorder histories. Subject chart will be reviewed to complete this data collection. A general physical examination and detailed neurological examination will be performed.
* Vitals: blood pressure, temperature, respiratory rate, weight and height will be collected.
* Polysomnography/electroencephalography (PSG/EEG): clinician Investigator will determine if subject is candidate for the procedure. A sleep study records the brain electrical waves, the oxygen level in the blood, heart rate and breathing, as well as eye and leg movements. Subject will need to be admitted overnight for the sleep study. The exam is video recorded.
* Blood samples: A single blood sample of 15 cc (not exceeding 3 cc per kg) (\~3 teaspoons) will be collected for research purposes. Samples will be kept up to 2 years after the study results are published.
* Optional skin biopsy: a skin biopsy from the upper, inner arm, lateral upper thigh, or another area, may be performed for research purposes. 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.

Conditions

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RAI1 Gene 17P11.2 Deletion+Duplication

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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).

Electroencephalography/Polysomnography (EEG/PSG)

Intervention Type 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.

Skin Biopsy

Intervention Type 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.

Blood draw

Intervention Type 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

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.

Blood draw

Intervention Type 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.

Interventions

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Electroencephalography/Polysomnography (EEG/PSG)

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.

Intervention Type DIAGNOSTIC_TEST

Skin Biopsy

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.

Intervention Type PROCEDURE

Blood draw

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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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sleep study

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

1 Month

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Doris Duke Charitable Foundation

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Davut Pehlivan

MD, Assistant Professor, Pediatrics-Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Davut Pehlivan, MD

Role: PRINCIPAL_INVESTIGATOR

Texas Children's Hospital - Baylor College of Medicine

Locations

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Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Davut Pehlivan, MD

Role: CONTACT

(713) 798-6970

Facility Contacts

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Davut Pehlivan, MD

Role: primary

(713) 798-6970

Other Identifiers

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H-54820 / RAI1

Identifier Type: -

Identifier Source: org_study_id

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