Clinical trial NCT05175664: Novel Diagnostic and Disease Stage Biomarkers in AD
Official title: TRacking Alzheimer´s Disease: a Study of Disease trajeCtory and Development of Diagnostic and Disease Stage biomarKers in AD (TRACK-AD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Neuro-Degenerative Diseases
Vascular Dementia
Dementia With Lewy Bodies
Healthy Controls
Keywords: Biomarkers
Pupillometry
Actigraphy
Blood-based biomarkers
Lead sponsor: Danish Dementia Research Centre
Sponsor class: NETWORK
First posted: 2022-01-04
Enrollment: 350
Sex: ALL
Minimum age (years): 30
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: In the longitudinal study (1) the investigators will include 100 patients diagnosed with mild cognitive impairment due to Alzheimer's disease or diagnosed with mild to moderate Alzheimer's disease. In the short-term study (2) the investigators will include 40 patients who are under investigation of a neurodegenerative disease. In the cross-sectional study (3) the investigatorswill include 50 patients with Alzheimer's disease, 50 healthy controls without brain disease, and 100 patients with other forms of dementia (dementia with Lewy body, vascular dementia, normal pressure hydrocephalus, frontotemporal dementia).

Brief summary: This study will investigate the efficacy of novel biomarkers, namely blood-based biomarkers, pupillometry and actigraphy to track and predict progression of Alzheimer's disease (AD). Furthermore, the study will investigate the diagnostic value of pupillometry and actigraphy for AD.

Detailed description: This study consist of three sub-studies.

In study 1, participants diagnosed with mild cognitive impairment due to AD or mild to moderate AD will be followed for up to 24 months with repeated blood samples, pupillometry, actigraphy, cognitive tests and a control brain scan.

In study 2, patients under investigation of a neurodegenerative disease who have a planned lumbar puncture in the Memory clinic will be invited to this study. Participants will undergo pupillometry and blood samples two times approximately one and four weeks after the lumbar puncture.

In study 3, participants with a dementia diagnosis will undergo pupillometry and actigraphy at a single visit.

Eligibility criteria: 1. Longitudinal study:

   Inclusion criteria:
   * MCI due to AD, or mild or moderate AD dementia according to the National Institute on Aging and Alzheimer's Association (NIA-AA) diagnostic criteria
   * Caregiver willing to participate as an informant
   * MMSE \>19 at inclusion
   * Brain FDG-PET/MRI or FDG/PET-CT
   * Able to cooperate to the investigations and give informed consent

   Exclusion criteria:
   * Other neurological or psychiatric illness that may affect neurofilament light (NfL) levels (severe neuropathy, multiple sclerosis (MS), stroke within the last 3 months, Wernicke encephalopathy)
   * Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
   * Excessive alcohol intake or substance abuse within the last 2 years
   * Ophthalmological disorders that may affect pupillometry
   * Participating in drug trials or other intervention trials
2. Short-term study:

   Inclusion criteria:
   * Patients under investigation of a neurodegenerative disease
   * MMSE \>19
   * Scheduled lumbar puncture/lumbar puncture performed within the last week prior to inclusion
   * Written consent form to the Danish Dementia Biobank
   * Able to cooperate to the investigations

   Exclusion criteria:
   * Other neurological or psychiatric illness that may affect NfL levels (severe neuropathy, MS, stroke within the last 3 months, Wernicke encephalopathy)
   * Excessive alcohol intake or substance abuse within the last 2 years
   * Ophthalmological disorders that may affect pupillometry
   * Participating in drug trials or other intervention trials
3. Cross-sectional study:

Inclusion criteria - Patients:

* A diagnosis of a dementia disorder
* Caregiver willing to participate as an informant
* MMSE \>15 at inclusion
* Able to cooperate to the investigations
* Able to give informed consent

Exclusion criteria - Patients:

* Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
* Excessive alcohol intake or substance abuse within the last 2 years
* Other known brain disorder
* Ophthalmological disorders that may affect pupillometry
* Participating in drug trials or other intervention trials

Inclusion criteria - Healthy Controls:

* Able to cooperate to the investigations
* Normal cognition
* Age 50-90 year

Exclusion criteria - Healthy Controls:

* Diagnosis of previous or current major psychiatric disorder (schizophrenia, bipolar disorder, psychosis) within last 2 years
* Excessive alcohol intake or substance abuse within the last 2 years
* Other known brain disorder
* Ophthalmological disorders that may affect pupillometry

Primary outcomes:
measure: Changes in CDR
timeFrame: Two years
Secondary outcomes:
measure: Changes in MMSE
timeFrame: Two years
measure: Changes in MR brain scan
timeFrame: 12 months
measure: FDG-PET brain scan
timeFrame: 12 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Dementia Research Centre
Study officials:
affiliation: Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark
name: Frederikke Kragh Clemmensen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark
name: Mathias Holsey Gramkow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark
name: Kristian Steen Frederiksen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark
name: Steen Gregers Hasselbalch, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark
name: Anja Hviid Simonsen, MSc Pharm PhD
role: PRINCIPAL_INVESTIGATOR
References: