Clinical trial NCT05740683: Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA
Official title: Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Idiopathic Anosmia
Idiopathic Hyposmia
Idiopathic Olfactory Dysfunction
Keywords: RT-QuIC
alpha-synuclein
Idiopathic anosmia
Idiopathic hyposmia
Idiopathic olfactory dysfunction
Prodromal Parkinsons disease
Prodromal dementia with Lewy bodies
Lead sponsor: Danish Dementia Research Centre
Sponsor class: NETWORK
Collaborators: name: Danish Reference Center for Prion Diseases, Rigshospitalet
name: Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
First posted: 2023-02-23
Enrollment: 100
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Fifty patients with idiopathic olfactory dysfunction (iOD) will be recruited from an anosmia clinic and community with posters in relevant newspapers and clinics. Also, 50 controls will be recruited from the community with posters in relevant newspapers and clinics.

Brief summary: Test of early warning signs and RT-QuIC in patients with idiopathic olfactory dysfunction

Detailed description: Background. The number of persons living with dementia is increasing in Denmark and worldwide because the population is generally growing older. Dementia with Lewy bodies (DLB) is the second most prevalent etiology among the neurodegenerative diseases that give rise to dementia.

DLB is characterized by many prodromal symptoms years before dementia is evident. Currently, little is known about the course of symptoms in the prodromal phase, and furthermore, the diagnosis of DLB can be clinically challenging, especially in the early stages. DLB is like Parkinson's disease (PD), characterized by the accumulation of alpha-synuclein, which misfolds and aggregates within neurons in so-called Lewy Bodies; this assumably drives the neurodegeneration. A novel technique for the measurement of misfolded alpha-synuclein is Real-Time Quaking-Induced Conversion (RT-QuIC), which may be able to support the diagnostic process as well as aid in identifying patients with prodromal DLB. This would enable earlier symptomatic relief and care and potentially promote the search for disease-modifying therapies, which is currently absent.

Objectives. The overarching objective of this project is to identify early clinical warning signs and biomarkers in prodromal DLB.

Method. Study 1: Exploratory cross-sectional case-control study of patients with olfactory dysfunction versus individuals without olfactory dysfunction assessing pathological alpha-synuclein by RT-QuIC and prodromal symptoms of DLB and Parkinson's Disease.

Study 2: Longitudinal follow-up in Danish registries on diagnosing PD and dementia.

Eligibility criteria: Inclusion criteria with patients iOD:

* Age 55 -75 years of age
* Slowly progressing and non-fluctuating iOD
* Able to give informed consent and to cooperate as evaluated by the PI

Exclusion criteria with patients iOD:

* Diagnosed with a neurodegenerative disease or major neurological/psychiatric condition.
* Anosmia/hyposmia caused by sino-nasal disease (including chronic rhinitis and allergy), after trauma, infection, congenial, olfactory dysfunction due to surgery, or toxins/drugs affecting the olfactory function.
* Olfactory dysfunction with response to systemic or local corticosteroids if tried
* Severe nasal cavity abnormalities or infections.
* Overt signs of dementia or PD
* Current alcohol or drug abuse
* Terminal illness
* Diagnosed with neurodegenerative disease or major neurological/psychiatric condition.

Inclusion criteria controls:

* Age 55 -75 years of age
* Able to give informed consent
* Able to cooperate as evaluated by the PI

Exclusion criteria controls:

* Olfactory dysfunction on clinical test
* Overt signs of dementia or PD
* Severe nasal cavity abnormalities or infections.
* Current alcohol or drug abuse
* Diagnosed with neurodegenerative disease or major neurological/psychiatric condition.

Primary outcomes:
measure: Real-time quaking-induced conversion (RT-QuIC) positive for alpha-synuclein (aSyn)
timeFrame: 24 months
measure: Diagnosis of Parkinson's disease (PD) or dementia
timeFrame: 8 years
Secondary outcomes:
measure: Smell test
timeFrame: 24 months
measure: Smell test
timeFrame: 24 months
measure: Motor function
timeFrame: 24 months
measure: Dysautonomia and non-motor symptoms
timeFrame: 24 months
measure: Subjective motor symptoms
timeFrame: 24 months
measure: Cognition
timeFrame: 24 months
measure: Prodromal PD
timeFrame: 24 months
measure: REM-sleep
timeFrame: Ever
measure: Color vision
timeFrame: Now
measure: Co-morbidities and medication
timeFrame: 10 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Dementia Research Centre
city: Copenhagen
country: Denmark
facility: Oskar McWilliam
Study officials:
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Kristian S Frederiksen
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Oskar McWilliam
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Steen G Hasselbalch
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Gunhild Waldemar
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Marie Brunn
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Capital Region
name: Anja H Simmonsen
role: PRINCIPAL_INVESTIGATOR
References: