Clinical trial NCT04950946: GNAO1 Natural History Study
Official title: Natural History of GNAO1-associated Neurodevelopmental Disorder
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: GNAO1
Keywords: Natural History Study
pediatric
neurology
movement disorder
epilepsy
GNAO1
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: The Bow Foundation
First posted: 2021-07-06
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Inability to obtain informed consent from parents or adult subjects.
* Inability to obtain medical records.

Primary outcomes:
measure: Chorea
timeFrame: March 2019; May-Oct 2020
measure: Dystonia
timeFrame: March 2019; May-Oct 2020
measure: Gross motor development, mobility
timeFrame: March 2019; May-Oct 2020
measure: Spasticity
timeFrame: March 2019
measure: Fine motor development
timeFrame: March 2019
measure: Quality of Life and Caregiver Burden
timeFrame: March 2019; May-Oct 2020
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Amy Viehoever, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Feng 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.
citation: Saitsu 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.
citation: Narayanan 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.