GNAO1GNAO1NCT04950946
GNAO1 Natural History Study
An observational study of GNAO1, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of the GNAO1 Natural History Study is to establish the clinical phenotype of GNAO1 associated neurologic disease, its association with genotype, and areas of clinical importance within the disease. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- GNAO1
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Feb 2019to Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Minors and adults who have a confirmed pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 (e.g. global developmental delay, movement disorder, seizures) as determined by study physicians.
Who may be able to join
- Enrollment in the Bow Foundation GNAO1 registry.
- Evidence of a known pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 as determined by study physicians.
Who cannot join
- Inability to obtain informed consent from parents or adult subjects.
- Inability to obtain medical records.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Natural History of GNAO1-associated Neurodevelopmental Disorder
The purpose of the GNAO1 Natural History Study is to establish the clinical phenotype of GNAO1 associated neurologic disease, its association with genotype, and areas of clinical importance within the disease.
Read the detailed description
GNAO1 associated neurologic disease is a rare autosomal dominant neurodevelopmental disorder characterized genetically by heterozygous de novo mutations in GNAO1 gene which encodes Gαo, the α subunit of Go, a G protein signal transducer. Phenotypically, it is characterized by developmental delay, epilepsy and/or movement disorder. Medical therapy is symptomatic and often ineffective for many patients. While there are basic and translational studies underway to develop more mechanistic treatments aimed at developing disease modifying treatments, our general knowledge of the natural history of GNAO1 associated neurologicis is extremely limited, making it difficult to select the best measures for identifying changes over time. Without this information,it will be difficult to detect any potential therapeutic efficacy in future trials of novel therapies. To address this critical void in our understanding, we propose to retrospectively and prospectively examine symptom progression(short-and long-term)and developmental outcomes in patients with GNAO1 associated neurologic disease. Retrospective data will be collected on a cohort of 50 patients. Standardized historical clinical information will be received from the physicians and care-givers of these patients, in collaboration with the Bow Foundation Registry. These data will provide an overview of the onset and severity of symptoms over development. In addition, prospective data will be acquired during in-person clinical evaluations of a cohort of 15-20 patients who are not receiving any experimental interventions. In combination, these two approaches will provide critical information about the natural history of GNAO1 associated neurologic disease in children, identify metrics that track change most reliably over time, and collect pilot data for larger future studies.
- Conditions
- GNAO1
- Keywords
- Natural History Study, pediatric, neurology, movement disorder, epilepsy, GNAO1
- Medical subject headings
- Movement Disorders, Epilepsy
What is being measured
The primary outcome is the main question the study is designed to answer.
Chorea
The Abnormal Involuntary Movement Scale (AIMS) assesses the severity of dyskinesias, as well as the overall severity, incapacitation, and the subject's level of awareness of the movements, and distress associated with them.
Measured: March 2019; May-Oct 2020
Dystonia
The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) assesses the severity of dystonia in nine body regions. The scale takes into account the severity and frequency of the dystonic movements.
Measured: March 2019; May-Oct 2020
Gross motor development, mobility
The Gross Motor Function Measure (GMFM-88) is a standardized observational instrument designed and validated to measure changes in gross motor function over time in children with cerebral palsy.
Measured: March 2019; May-Oct 2020
Spasticity
The Modified Ashworth Scale (MAS) is a muscle tone assessment scale used to assess the resistance experienced during passive range of motion. The MAS is the current standard for clinical assessment of extremity spasticity.
Measured: March 2019
Fine motor development
The Peabody Developmental Motor Scales 2nd Edition (PDMS-2) is an early childhood motor development program that provides both in-depth assessment and training or remediation of gross and fine motor skills. The assessment is composed of six subtests that measure interrelated motor abilities that develop early in life. We are mainly interested in two subtests: Grasping and Visual-Motor Integration.
Measured: March 2019
Quality of Life and Caregiver Burden
The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire attempts to understand and quantitate the quality of life of patients and caregiver burden.
Measured: March 2019; May-Oct 2020
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2021
- Study start18 Feb 2019
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for GNAO1Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Bow Foundation
- Responsible party
- Sponsor
- Investigators
- Amy Viehoever, MD, Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04950946
- Sponsor's protocol ID
- 201901128
- Acronym
- GNAO1
- Status last verified
- Jun 2021
- First submitted
- 25 Jun 2021
- Last updated
- 6 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ananth AL, Robichaux-Viehoever A, Kim YM, Hanson-Kahn A, Cox R, Enns GM, Strober J, Willing M, Schlaggar BL, Wu YW, Bernstein JA. Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder. Pediatr Neurol. 2016 Jun;59:81-4. doi: 10.1016/j.pediatrneurol.2016.02.018. Epub 2016 Mar 17.
PubMed 27068059Feng H, Sjogren B, Karaj B, Shaw V, Gezer A, Neubig RR. Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology. 2017 Aug 22;89(8):762-770. doi: 10.1212/WNL.0000000000004262. Epub 2017 Jul 26.
PubMed 28747448Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina M, Ogata K, Matsumoto N. Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay. Eur J Hum Genet. 2016 Jan;24(1):129-34. doi: 10.1038/ejhg.2015.92. Epub 2015 May 13.
PubMed 25966631Narayanan UG, Fehlings D, Weir S, Knights S, Kiran S, Campbell K. Initial development and validation of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Dev Med Child Neurol. 2006 Oct;48(10):804-12. doi: 10.1017/S0012162206001745.
PubMed 16978459
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History of GNAO1-associated Neurodevelopmental Disorder
- ClinicalTrials.gov ID
- NCT04950946
- Acronym / sponsor ID
- GNAO1 / 201901128
- Conditions
- GNAO1
- Keywords
- Natural History Study, pediatric, neurology, movement disorder, epilepsy, GNAO1
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- The Bow Foundation
- Study start
- 18 Feb 2019 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 6 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the GNAO1 Natural History Study is to establish the clinical phenotype of GNAO1 associated neurologic disease, its association with genotype, and areas of clinical importance within the disease.
Detailed description
GNAO1 associated neurologic disease is a rare autosomal dominant neurodevelopmental disorder characterized genetically by heterozygous de novo mutations in GNAO1 gene which encodes Gαo, the α subunit of Go, a G protein signal transducer. Phenotypically, it is characterized by developmental delay, epilepsy and/or movement disorder. Medical therapy is symptomatic and often ineffective for many patients. While there are basic and translational studies underway to develop more mechanistic treatments aimed at developing disease modifying treatments, our general knowledge of the natural history of GNAO1 associated neurologicis is extremely limited, making it difficult to select the best measures for identifying changes over time. Without this information,it will be difficult to detect any potential therapeutic efficacy in future trials of novel therapies. To address this critical void in our understanding, we propose to retrospectively and prospectively examine symptom progression(short-and long-term)and developmental outcomes in patients with GNAO1 associated neurologic disease. Retrospective data will be collected on a cohort of 50 patients. Standardized historical clinical information will be received from the physicians and care-givers of these patients, in collaboration with the Bow Foundation Registry. These data will provide an overview of the onset and severity of symptoms over development. In addition, prospective data will be acquired during in-person clinical evaluations of a cohort of 15-20 patients who are not receiving any experimental interventions. In combination, these two approaches will provide critical information about the natural history of GNAO1 associated neurologic disease in children, identify metrics that track change most reliably over time, and collect pilot data for larger future studies.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Minors and adults who have a confirmed pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 (e.g. global developmental delay, movement disorder, seizures) as determined by study physicians.
Key inclusion criteria (2 listed)
- Enrollment in the Bow Foundation GNAO1 registry.
- Evidence of a known pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 as determined by study physicians.
Key exclusion criteria (2 listed)
- Inability to obtain informed consent from parents or adult subjects.
- Inability to obtain medical records.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Chorea
Time frame: March 2019; May-Oct 2020
The Abnormal Involuntary Movement Scale (AIMS) assesses the severity of dyskinesias, as well as the overall severity, incapacitation, and the subject's level of awareness of the movements, and distress associated with them.
Dystonia
Time frame: March 2019; May-Oct 2020
The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) assesses the severity of dystonia in nine body regions. The scale takes into account the severity and frequency of the dystonic movements.
Gross motor development, mobility
Time frame: March 2019; May-Oct 2020
The Gross Motor Function Measure (GMFM-88) is a standardized observational instrument designed and validated to measure changes in gross motor function over time in children with cerebral palsy.
Spasticity
Time frame: March 2019
The Modified Ashworth Scale (MAS) is a muscle tone assessment scale used to assess the resistance experienced during passive range of motion. The MAS is the current standard for clinical assessment of extremity spasticity.
Fine motor development
Time frame: March 2019
The Peabody Developmental Motor Scales 2nd Edition (PDMS-2) is an early childhood motor development program that provides both in-depth assessment and training or remediation of gross and fine motor skills. The assessment is composed of six subtests that measure interrelated motor abilities that develop early in life. We are mainly interested in two subtests: Grasping and Visual-Motor Integration.
Quality of Life and Caregiver Burden
Time frame: March 2019; May-Oct 2020
The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire attempts to understand and quantitate the quality of life of patients and caregiver burden.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Background: PubMed 27068059Ananth AL, Robichaux-Viehoever A, Kim YM, Hanson-Kahn A, Cox R, Enns GM, Strober J, Willing M, Schlaggar BL, Wu YW, Bernstein JA. Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder. Pediatr Neurol. 2016 Jun;59:81-4. doi: 10.1016/j.pediatrneurol.2016.02.018. Epub 2016 Mar 17.
- Background: PubMed 28747448Feng H, Sjogren B, Karaj B, Shaw V, Gezer A, Neubig RR. Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology. 2017 Aug 22;89(8):762-770. doi: 10.1212/WNL.0000000000004262. Epub 2017 Jul 26.
- Background: PubMed 25966631Saitsu H, Fukai R, Ben-Zeev B, Sakai Y, Mimaki M, Okamoto N, Suzuki Y, Monden Y, Saito H, Tziperman B, Torio M, Akamine S, Takahashi N, Osaka H, Yamagata T, Nakamura K, Tsurusaki Y, Nakashima M, Miyake N, Shiina M, Ogata K, Matsumoto N. Phenotypic spectrum of GNAO1 variants: epileptic encephalopathy to involuntary movements with severe developmental delay. Eur J Hum Genet. 2016 Jan;24(1):129-34. doi: 10.1038/ejhg.2015.92. Epub 2015 May 13.
- Background: PubMed 16978459Narayanan UG, Fehlings D, Weir S, Knights S, Kiran S, Campbell K. Initial development and validation of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Dev Med Child Neurol. 2006 Oct;48(10):804-12. doi: 10.1017/S0012162206001745.
- The Bow Foundation websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Viehoever, MD, Ph.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of GNAO1, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chorea (time frame: March 2019; May-Oct 2020). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04950946, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2021.