Clinical trial NCT05262543: PREdictive Risk Factors of Conversion Into Idiopathic RBD. Italian Study
Official title: Redictive Risk Factors of Conversion Into Idiopathic RBD. Italian Study [FAttori di Rischio PREdittivi di Conversione Nell'RBD Idiopatico. STudio ItalianO
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: REM Sleep Behavior Disorder
Keywords: atonia
neurodegeneration
Lead sponsor: University of Cagliari
Sponsor class: OTHER
Collaborators: name: University of Bologna
name: University of Genova
name: University of Pavia
name: Istituto Auxologico Italiano
First posted: 2022-03-02
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients, aged major of 18 years old, diagnosed with iRBD, that can provide informed consent referring to centers participating in the FARPRESTO study

Brief summary: REM Sleep Behavior Disorder (RBD) is a REM sleep parasomnia first described in 1986 and characterized by the loss of physiological muscle atonia typical of REM sleep and by the presence of abnormal, sometimes violent, motor activity often related to dream content The observed motor behaviors are often associated to vivid dreams, characterized by an aggressive-defensive content, even if pleasant dreams have been described, resulting in non-violent behaviors. Diagnosis of RBD requires video-polysomnographic recording (vPSG) at a Sleep Center, essential to identify and quantify the complete or intermittent loss of physiological muscle atonia during REM sleep (REM sleep without atonia, RSWA) and record any related motor behaviors. The exact prevalence of RBD in the general population is not known and it seems underrated, but is estimated to be 0.3-1.15%. RBD is defined as idiopathic or isolated (iRBD) when it is not associated with other neurological diseases. The so-called symptomatic RBD, on the other hand, can occur in association with neurodegenerative diseases of the spectrum of alpha-synucleinopathies which include Parkinson's Disease (PD), Multiple System Atrophy (AMS), and Lewy Body Dementia (DLB). In recent years, several follow-up studies on large cohorts of iRBD patients have shown that the idiopathic form evolves towards a symptomatic form in most cases. More precisely, the risk of developing an alpha-synucleinopathies increases over time, with a conversion rate of up to 90% in some studies at 14 years. RBD represents an early marker of neurodegeneration, like a unique open window on the initial, pre-symptomatic phase of alpha-synucleinopathies, which could allow the use of neuroprotective therapies, as soon as they are available. Several longitudinal studies indicated older age, presence of hyposmia, abnormal color vision, minimal extrapyramidal motor signs, mild cognitive impairment, autonomic disturbances, and severity of loss of RSWA as risk factors for neurodegeneration. However, most studies investigated biomarkers separately, with retrospective study designs, in small cohorts or without a rigorous harmonization between centers in the case of multicenter studies.

To date, however, there is no reliable pool of biomarkers that predict the phenoconversion into α-synucleinopathy, the timing in which this can occur, and the phenotype of α-synucleinopathy. Furthermore, despite clinical and research evidence suggesting that iRBD is a heterogeneous disorder little attention was paid to different iRBD phenotypes and currently, there are no relevant data on the impact of iRBD on quality of life.

Actually, through neural network analysis approaches, it is possible to find out complex correlations between data from different sources (i.e., clinical examinations, questionnaires, biological data, imaging and neurophysiological techniques, etc.) and to identify subgroups of patients sharing the same substantial characteristics. Identifying different iRBD phenotypes through established as well as innovative biomarkers and standardized measures of wellbeing is crucial to better understanding alpha-synucleinopathies, developing targeted interventions, and reducing the disease burden.

To this aim, clinical, biological, neurophysiological, neuropsychological and imaging biomarkers need to be prospectively collected, according to standardized and harmonized procedures. This would significantly increase our understanding of the physiopathological processes of alpha-synucleinopathy from the prodromal phase. Indeed, identifying phenotype clusters with both consolidated and innovative biomarkers may lay the groundwork for a reliable characterization of iRBD patients, likely providing the basis for an efficient stratification of patients longitudinally followed.

Several disease-modifying therapies are now in development, including but not limited to monoclonal antibodies against alpha-synucleinopathy. Prodromal synucleinopathy patients, such as those with iRBD, are the ideal target to test disease-modifying therapies because the neurodegeneration is still in an early stage and the likelihood to rescue both brain structures and function is higher. The last aim of the FarPResto study is to have a trial-ready cohort of iRBD patients, collected with standardized and harmonized procedures, to be enrolled in upcoming disease-modifying trials.

The FARPRESTO project is endorsed by the Italian Association of Sleep Medicine (AIMS) and by The RBD_Patients society (www.sonnomed.it)


Eligibility criteria: Inclusion Criteria:

* Age: major of 18 years old
* iRBD diagnosis, according to diagnostic criteria of the ICSD second and third edition

Exclusion Criteria:

* Impossibility to provide or withdraw informed consent and inability to read, write and understand the purpose and modality of the study.

Primary outcomes:
measure: Identification of predictive risk factors of phenoconversion in patients with iRBD
timeFrame: May 25, 2020 - January 31, 2035
Secondary outcomes:
measure: Description of the socio-demographic and clinical characteristics of patients diagnosed with iRBD
timeFrame: May 25, 2020 - January 31, 2035
measure: Collection of longitudinal data about the development of alpha-synucleinopathies and estimation of the conversion rate at 3, 5, 7, and 10 years
timeFrame: May 25, 2020 - January 31, 2035
measure: Evaluation of the impact of iRBD on the quality of life and sleep
timeFrame: May 25, 2020 - January 31, 2035
measure: Assessment of the correlation between phenoconversion, cognitive performance and loss of normal muscle atony during REM sleep
timeFrame: May 25, 2020 - January 31, 2035
measure: Identification of RBD phenotypes through different biomarkers
timeFrame: May 25, 2020 - January 31, 2035
measure: Validation of vPSG criteria for RBD diagnosis
timeFrame: May 25, 2020 - January 31, 2035
Other outcomes:
Locations:
city: Oggebbio
country: Italy
facility: IRCCS Auxologico Piancavallo
state: Verbania
city: Cagliari
country: Italy
facility: Centro Interdipartimentale di Medicina del Sonno, Università degli studi di Cagliari
Study officials:
affiliation: University of Cagliari
name: Monica Puligheddu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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