Alpha-synuclein Rt-quic and Neurologic Symptoms in Persons With idiOpathic anosMiA (AROMA)

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

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Anosmia; Idiopathic Hyposmia; Idiopathic Olfactory Dysfunction
• Intervention / Treatment: Diagnostic test: RT-QuiC

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Oskar McWilliam; Phone Number: +4535458759; Email: oskar.mcwilliam@regionh.dk
• Study Contact Backup: Name: Kristian S Frederiksen; Email: Kristian.Steen.Frederiksen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Danish Dementia Research Centre
    • Contact: Steen Gregers Hasselbalch, DMSc; Phone Number: +45 35 45 69 22; Email: steen.gregers.hasselbalch@regionh.dk
    • Contact: Kristian Steen Frederiksen, MD, PhD; Phone Number: +4535456922; Email: kristian.steen.frederiksen@regionh.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Oskar McWilliam
    • Contact: Gunhild Waldemar; Email: Gunhild.Waldemar.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
People with idiopathic olfactory dysfunction	Diagnostic test: RT-QuiC; RT-QuIC measures the ability of aSyn to misfold other aSyn proteins and is an amplification technique.
People without olfactory dysfunction	Diagnostic test: RT-QuiC; RT-QuIC measures the ability of aSyn to misfold other aSyn proteins and is an amplification technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-time quaking-induced conversion (RT-QuIC) positive for alpha-synuclein (aSyn)		24 months
Diagnosis of Parkinson's disease (PD) or dementia	A diagnosis of PD or dementia in national databases.	8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smell test	Sniffin Sticks identification test (SIT16)	24 months
Smell test	Sniffin Sticks 48	24 months
Motor function	Unified Parkinson's Rating Scale (UPDRS-III)	24 months
Dysautonomia	Unified Parkinson's Rating Scale (UPDRS-I)	24 months

Collaborators and Investigators

• Sponsor: Danish Dementia Research Centre
• Collaborators: Danish Reference Center for Prion Diseases, Rigshospitalet; Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Rigshospitalet
• Investigators: Principal Investigator: Kristian S Frederiksen, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Oskar McWilliam, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Steen G Hasselbalch, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Gunhild Waldemar, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Marie Brunn, Danish Dementia Research Centre, Rigshospitalet, Capital Region; Principal Investigator: Anja H Simmonsen, Danish Dementia Research Centre, Rigshospitalet, Capital Region

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): December 1, 2032
• Study Completion (Anticipated): December 1, 2032

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: alpha-synuclein; RT-QuIC; Idiopathic anosmia; Idiopathic hyposmia; Idiopathic olfactory dysfunction; Prodromal Parkinsons disease; Prodromal dementia with Lewy bodies
• Additional Relevant MeSH Terms: Nervous System Diseases; Sensation Disorders; Olfaction Disorders; Neurologic Manifestations; Anosmia
• Other Study ID Numbers: H-22053428

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No