Circadian Rhythm and Other Factors in Memory Clinic Patients

Dementia Clinical Trial

— CIRCAME  

Official title:

Circadian Rhythm and Other Individual Factors Among Memory Clinic Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05977712
• Other study ID #: APHP230740
• Secondary ID: 2023-A01469-36
• Status: Recruiting
• Start date: March 6, 2024
• Est. completion date: March 2042

Study information

• Verified date: March 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Claire PAQUET, MDPhD
• Phone: 0140054313
• Email: claire.paquet[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The CIRCAME study is a bicentric study of patients from 2 memory clinics in Paris. The main objective is to identify circadian rhythm components and other individual risk factors (sociodemographic, behavioral, and health related factors) associated with the diagnosis of subtypes (AD, Lewy bodies, vascular, frontotemporal dementia) and stages (cognitively healthy, mild cognitive impairment, clinical dementia) of dementia, independent of known risk factors (sociodemographic and genetic) and assess the relevance of use of these factors in primary care for screen of dementia including subtypes and stages. A secondary objective is to determine factors associated with progression of the disease, in terms of cognitive decline and limitations in activities of daily living, as well as progression to dementia among cognitively healthy controls and patients with mild cognitive impairment, up to 15 years after the inclusion period.

Description:

The diagnosis of Alzheimer's disease and other related dementias is mainly based on assessment of cognitive, behavioral and neuropsychological symptoms, functional limitations and imaging data/cerebrospinal fluid (CSF) biomarkers in some cases. These measures are primarily used in specialized clinics leading to a potential large number of dementia cases not being diagnosed. With population ageing, the number of people living with dementia is increasing and there is an urgent need for cost-effective, scalable tool for early, accurate screening of dementia cases, including both AD and other types of dementia, in primary care. Furthermore, the factors associated with the progression of the different types of dementia are still poorly understood, limiting the prospects for intervention to improve the quality of life of patients and their caregivers and to slow the progression of the disease.

This project aims to identify circadian rhythm components and other individual risk factors that could be used in primary care for dementia diagnosis (including its subtypes: AD, Lewy bodies, vascular, frontotemporal dementia) and stages (cognitively healthy, mild cognitive impairment, clinical dementia). A secondary objective is to determine factors associated with progression of the disease, in terms of cognitive decline and limitations in activities of daily living, as well as progression to dementia among cognitively healthy controls and patients with mild cognitive impairment.

This will be achieved using data from 1500 patients from 2 memory clinics in Paris from who data on sociodemographic, behavioral, and health related factors (such as reported sleep disturbance, plasma biomarkers, retina measures (in a subsample, CIRCAME-EYE)) will be measured at inclusion interview. Baseline examination will also include a wrist-mounted device for a measure of circadian rhythm and its related behaviors (physical activity and sleep), for which disruptions are thought to characterize dementia subtypes and stages. Information on dementia diagnosis and stages will come from memory clinic routine visits at the time of the inclusion; they will include subtypes (AD, Lewy bodies, vascular, frontotemporal dementia), cognitive stages (cognitively healthy, mild cognitive impairment, clinical dementia) and AD stages based on CSF biomarkers and clinical measures. Information on progression of the disease (change in cognitive function using the mini-mental status examination, change in limitations in activity of daily living) and incidence of dementia, institutionalization and mortality will be retrieved from patients' routine visits at memory clinics up to 15 years after the inclusion period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: March 2042
• Est. primary completion date: March 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient of legal age (18 or over)

• Signed informed consent form

• Patient affiliated to the french social security system

Exclusion Criteria:

• Skin allergy to plastic

• Diagnosis of psychiatric disorder that can explain all cognitive symptoms

• Inability to come accompanied for patients with a Mini-Mental State Examination (MMSE) cognitive score =20 or a clinician assessment indicating the need to be accompanied (e.g. wheelchair use, agitation)

• Patient of legal age and subject to a legal protection measure (guardianship, curatorship)

• Participation at the time of inclusion and during the 9-day period of wearing the accelerometer in interventional research with potential impact on circadian rhythm

Related Conditions & MeSH terms

• Dementia

Intervention

Other:
• Questionnaire
The questionnaire includes information on socio-demographics (age, sex, education, occupation, marital status), behavioural (smoking, alcohol consumption, social functioning), and health-related factors (morbidities, treatment, sleep disturbance, eye diseases, frailty, falls).
• Clinical examination
This includes earing test, cognitive tests (mini-mental status examination, MemScreen), body mass index, waist circumference, blood pressure and blood tests (biomarkers of Alzheimer's disease, neurodegeneration, and other dementias).
• Accelerometer port
Participants will be wearing an accelerometer for 9 days.
• Eye examination
Eye fundus photo, OCT and OCT-A exams

Locations

Country	Name	City	State
France	Centre de neurologie Cognitive / CMRR	Paris
France	Hôpital de Jour Gériatrique et consultation mémoire	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fondation Rothschild Paris, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dementia subtypes and stages	Dementia subtypes and stages will be defined on routine visits at the memory center and categorised as: Alzheimer's disease, vascular dementia, Lewy body dementia, frontotemporal dementia), as having mild cognitive impairment (differentiating AD form of MCI and others), or being cognitively healthy.; This outcome will be examined cross-sectionally first (at inclusion) and, among those with MCI and healthy controls, prospectively over time (up to 15 years after the inclusion period).	At inclusion (2024-2025), in 2026 and every 3 years up to 2042
Primary	Alzheimer's disease stages	AD stages will be based on CSF Aß peptide level (Aß42/40 ratio) to assess the A+ criterion, p-Tau 181 to assess the T+ criterion, and clinical examination to assess the CogFI+ criterion (cognitive impairment and/or neurobehavioural symptoms with functional impact on daily life).; This analysis will be among those with CSF biomarkers measured as part of their routine visit at the memory clinics.	At inclusion (2024-2025), in 2026 and every 3 years up to 2042
Secondary	Fluid based biomarkers of dementia	Association of the different exposure variables with plasma and csf biomarkers of dementia will be examined.; Plasma biomarkers include 1) Amyloid ß 42/40 ratio, a marker of AD pathology, although probably less robust than the CSF Aß 42/40 ratio; 2) phosphorylated tau (p-tau) for detection of early AD-related tauopathy and disease staging; 3) neurofilament light (NfL), a marker of neurodegeneration in all neurodegenerative diseases, and 4) glial fibrillary acidic protein (GFAP), a marker of astrocytosis, found as early as in pre-amyloid AD disease stages.; CSF biomarkers include Aß42 and Aß40 peptides, total and phosphorylated tau proteins (when done in routine care).	At inclusion
Secondary	Cognitive function	Cognitive tests include the mini-mental status examination test and the MemScreen test. They will be evaluated at inclusion and during routine visit at the memory clinics. Association with scores at inclusion and changes between inclusion and several time points will be examined.	At inclusion (2024-2025), and change between inclusion and 2026 and every 3 years up to 2042
Secondary	Limitations in activity of daily living (ADL) and instrumental activity of daily living (IADL)	Limitations in ADL (dressing, walking, bathing, eating, continence, using toilet) and IADL (cooking, shopping for grocery, telephone calls, taking medication, using transports, managing money).	At inclusion (2024-2025), and change between inclusion and 2026 and every 3 years up to 2042
Secondary	Institutionalization, hospitalization and death	Information will come from memory clinics and electronic health records.	Incidence between inclusion and 2026 and every 3 years up to 2042