Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS)
Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-023-09494-w |
| _version_ | 1797769676390924288 |
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| author | Jorrit Tjeertes Carlos A. Bacino Terry Jo Bichell Lynne M. Bird Mariana Bustamante Rebecca Crean Shafali Jeste Robert W. Komorowski Michelle L. Krishnan Meghan T. Miller David Nobbs Cesar Ochoa-Lubinoff Kimberly A. Parkerson Alexander Rotenberg Anjali Sadhwani Mark D. Shen Lisa Squassante Wen-Hann Tan Brenda Vincenzi Anne C. Wheeler Joerg F. Hipp Elizabeth Berry-Kravis |
| author_facet | Jorrit Tjeertes Carlos A. Bacino Terry Jo Bichell Lynne M. Bird Mariana Bustamante Rebecca Crean Shafali Jeste Robert W. Komorowski Michelle L. Krishnan Meghan T. Miller David Nobbs Cesar Ochoa-Lubinoff Kimberly A. Parkerson Alexander Rotenberg Anjali Sadhwani Mark D. Shen Lisa Squassante Wen-Hann Tan Brenda Vincenzi Anne C. Wheeler Joerg F. Hipp Elizabeth Berry-Kravis |
| author_sort | Jorrit Tjeertes |
| collection | DOAJ |
| description | Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms. Methods Fifty-five individuals with AS (aged < 5 years: n = 16, 5–12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1–12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits. Results The participants achieved high completion rates for the clinical outcome assessments (adherence: 89–100% [Clinic Visit 1]; 76–91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health technologies. The coronavirus disease 2019 (COVID-19) pandemic impacted participants’ uptake of and/or adherence to some measures. It also potentially impacted the at-home PSG/EEG recordings, which were otherwise feasible. Participants achieved Bayley-III results comparable to the available natural history data, showing similar scores between individuals aged ≥ 18 and 5–12 years. Also, participants without a deletion generally scored higher on most clinical outcome assessments than participants with a deletion. Furthermore, the observed AS EEG phenotype of excess delta-band power was consistent with prior reports. Conclusions Although feasible clinical outcome assessments and digital health technologies are reported herein, further improved assessments of meaningful AS change are needed. Despite the COVID-19 pandemic, remote assessments facilitated high adherence levels and the results suggested that at-home PSG/EEG might be a feasible alternative to the in-clinic EEG assessments. Taken altogether, the combination of in-clinic/at-home clinical outcome assessments, digital health technologies, and PSG/EEG may improve protocol adherence, reduce patient burden, and optimize study outcomes in AS and other rare disease populations. |
| first_indexed | 2024-03-12T21:12:28Z |
| format | Article |
| id | doaj.art-ef450fe783de498baf723d4e7e4e74fb |
| institution | Directory Open Access Journal |
| issn | 1866-1955 |
| language | English |
| last_indexed | 2024-03-12T21:12:28Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-ef450fe783de498baf723d4e7e4e74fb2023-07-30T11:08:02ZengBMCJournal of Neurodevelopmental Disorders1866-19552023-07-0115112110.1186/s11689-023-09494-wEnabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS)Jorrit Tjeertes0Carlos A. Bacino1Terry Jo Bichell2Lynne M. Bird3Mariana Bustamante4Rebecca Crean5Shafali Jeste6Robert W. Komorowski7Michelle L. Krishnan8Meghan T. Miller9David Nobbs10Cesar Ochoa-Lubinoff11Kimberly A. ParkersonAlexander Rotenberg12Anjali Sadhwani13Mark D. Shen14Lisa Squassante15Wen-Hann Tan16Brenda Vincenzi17Anne C. Wheeler18Joerg F. Hipp19Elizabeth Berry-Kravis20F. Hoffmann-La Roche LtdDepartment of Molecular and Human Genetics, Baylor College of MedicineCOMBINEDBrainDepartment of Pediatrics, University of California San DiegoF. Hoffmann-La Roche LtdIonis Pharmaceuticals IncChildren’s Hospital Los AngelesIonis Pharmaceuticals IncF. Hoffmann-La Roche LtdF. Hoffmann-La Roche LtdF. Hoffmann-La Roche LtdDepartments of Pediatrics, Division of Developmental-Behavioral Pediatrics, Rush University Medical CenterDepartment of Neurology, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Psychiatry and Behavioral Services, Boston Children’s Hospital, Harvard Medical SchoolCarolina Institute for Developmental Disabilities & UNC Neuroscience Center, University of North CarolinaF. Hoffmann-La Roche LtdDivision of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical SchoolF. Hoffmann-La Roche LtdCarolina Institute for Developmental DisabilitiesF. Hoffmann-La Roche LtdDepartments of Pediatrics, Neurological Sciences, Anatomy and Cell Biology, Rush University Medical CenterAbstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms. Methods Fifty-five individuals with AS (aged < 5 years: n = 16, 5–12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1–12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits. Results The participants achieved high completion rates for the clinical outcome assessments (adherence: 89–100% [Clinic Visit 1]; 76–91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health technologies. The coronavirus disease 2019 (COVID-19) pandemic impacted participants’ uptake of and/or adherence to some measures. It also potentially impacted the at-home PSG/EEG recordings, which were otherwise feasible. Participants achieved Bayley-III results comparable to the available natural history data, showing similar scores between individuals aged ≥ 18 and 5–12 years. Also, participants without a deletion generally scored higher on most clinical outcome assessments than participants with a deletion. Furthermore, the observed AS EEG phenotype of excess delta-band power was consistent with prior reports. Conclusions Although feasible clinical outcome assessments and digital health technologies are reported herein, further improved assessments of meaningful AS change are needed. Despite the COVID-19 pandemic, remote assessments facilitated high adherence levels and the results suggested that at-home PSG/EEG might be a feasible alternative to the in-clinic EEG assessments. Taken altogether, the combination of in-clinic/at-home clinical outcome assessments, digital health technologies, and PSG/EEG may improve protocol adherence, reduce patient burden, and optimize study outcomes in AS and other rare disease populations.https://doi.org/10.1186/s11689-023-09494-wAngelman syndromeEndpoint developmentEEGSleepDigital health technologyClinical outcome assessments |
| spellingShingle | Jorrit Tjeertes Carlos A. Bacino Terry Jo Bichell Lynne M. Bird Mariana Bustamante Rebecca Crean Shafali Jeste Robert W. Komorowski Michelle L. Krishnan Meghan T. Miller David Nobbs Cesar Ochoa-Lubinoff Kimberly A. Parkerson Alexander Rotenberg Anjali Sadhwani Mark D. Shen Lisa Squassante Wen-Hann Tan Brenda Vincenzi Anne C. Wheeler Joerg F. Hipp Elizabeth Berry-Kravis Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) Journal of Neurodevelopmental Disorders Angelman syndrome Endpoint development EEG Sleep Digital health technology Clinical outcome assessments |
| title | Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) |
| title_full | Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) |
| title_fullStr | Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) |
| title_full_unstemmed | Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) |
| title_short | Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) |
| title_sort | enabling endpoint development for interventional clinical trials in individuals with angelman syndrome a prospective longitudinal observational clinical study freesias |
| topic | Angelman syndrome Endpoint development EEG Sleep Digital health technology Clinical outcome assessments |
| url | https://doi.org/10.1186/s11689-023-09494-w |
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