Cohort Study of Adult Patients With Down Syndrome at Risk of Developing Alzheimer's Disease (TriAL21)

Sponsor

Institut Jerome Lejeune (Other)

Overall Status

Recruiting

CT.gov ID

NCT03901261

Collaborator

(none)

200

Enrollment

Location

Arm

47.1

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

TriAL21 study is an interventional, open, one arm, prospective, national and single center study.

A total of 200 patients with Down syndrome, aged 35 years and over, without diagnosis of Alzheimer's disease will be enrolled into the study.

Participating centre is Institut Jérôme Lejeune; outpatient's clinic dedicated to treating patients with cognitive deficiencies of genetic origin including patients with Down syndrome.

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome Alzheimer Disease	Procedure: Neuro-imaging, Lumbar puncture	N/A

Detailed Description

The aim of the study is to describe and follow a cohort of patients with Down syndrome without diagnosis of Alzheimer's disease at inclusion, in order to identify factors influencing the age of onset of the disease.

The total study duration will be approximately 4 years.

Inclusion period : 2 years
Follow-up period per patient : 2 years

Patients will be then followed during 10 years for routine medical follow-up. In case of Alzheimer's disease onset during this period, all data regarding diagnosis of AD will be collected for the study. Data about dementia evolution and mortality in case of AD diagnosis during the study will also be collected during this follow-up period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Interventional prospective monocentric, national open study with single armInterventional prospective monocentric, national open study with single arm

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Cohort Study of Adult Patients With Down Syndrome at Risk of Developing Alzheimer's Disease

Actual Study Start Date :

Apr 26, 2019

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Down syndrome patients	Procedure: Neuro-imaging, Lumbar puncture Optional Lumbar Puncture will be performed at inclusion visit Optional Neuro-Imaging (MRI (Magnetic Resonance Imaging) will be performed within 3 months after inclusion visit

Arm

Intervention/Treatment

Experimental: Down syndrome patients

Procedure: Neuro-imaging, Lumbar puncture

Optional Lumbar Puncture will be performed at inclusion visit Optional Neuro-Imaging (MRI (Magnetic Resonance Imaging) will be performed within 3 months after inclusion visit

Outcome Measures

Primary Outcome Measures

Age of onset of Alzheimer's disease [2 years]
age (year)
Gender that could influence the age of onset of the disease as determined by medical record review [2 years]
Level of intellectual diasability that could influence the age of onset of the disease as determined by medical record review [2 years]
Family history of Alzheimer's disease that could influence the age of onset of the disease as determined by medical record review [2 years]
Cardio-vascular risk factors that could influence the age of onset of the disease as determined by medical record review [2 years]
Down syndrome comorbidies that could influence the age of onset of the disease as determined by medical record review [2 years]
Genetic's factor other than APP that could influence the age of onset of the disease as determined by medical record review [2 years]
Head trauma that could influence the age of onset of the disease as determined by medical record review [2 years]
Age of menopause that could influence the age of onset of the disease as determined by medical record review [2 years]

Secondary Outcome Measures

Evaluation of neuropsychological evolution using Katz Index of Independence in Activities of Daily Living (Katz ADL) score [2 years]
Questionnaire about Activities of Daily Living such as bathing, toileting, continence, dressing, transferring and feeding Scoring : Independence: 1 point - Partial dependence 0.5 point - Full dependence: 0 point
Evaluation of neuropsychological evolution using Lawton-Brody Instrumental Activities of Daily Living scale ( IADL) [2 years]
Questionnaire about strumental Activities of Daily Living such as ability to use telephone, responsibility for taking medication, travels independently on public transportation, ability to handle finances Scoring : 0 or 1
Evaluation of neuropsychological evolution using Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) score [2 years]
Dementia Screening for Individuals with Intellectual Disabilities Questionnary is a autonomy and psychobeahavioral questionnaire to gather information from carers of people with Down's syndrome about the symptoms of dementia
Evaluation of neuropsychological evolution using Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities score [2 years]
Camdex-Ds. Based on an informant interview to aid the diagnosis of dementia in people with DS according to the DSM-IV et ICD criteria for dementia.
Evaluation of neuropsychological evolution using Cambridge Cognition Examination score [2 years]
It is part of the CAMDEX-DS. Section 2 involves the direct assessment of patient. It contains seven different subscales and has 46 items. it gives a total score of 108. Decline between assessment at Time 1 and assessment at time 2 in association with CAMDEX confirm or evoque the AD diagnosis.
Evaluation of neuropsychological evolution using Cued Recall test score [2 years]
It is a memory task. It consists in 12 items accompanied by a unique category cue, presented four a time in three trials. It generates two measures respectively for learning phase and delayed recall: a free recall score/12 and a total score/36 (FRS plus items recalled with cue) for the learnig phase. A free recall (FRS/12) and a total score (FRS plus items recalled with cue /12) for the delayed recall. Number of intrusions will be also recorded.
Evaluation of neuropsychological evolution using Cancellation task [2 years]
Measure of task accuracy (total number of correct responses, range score 0-16) and total time performance (in seconds) were included in the analyses.
Evaluation of neuropsychological evolution using Leiter III assessment score [2 years]
It is a nonverbal measure of intelligence & cognitive abilities. It includes four subtests whose raw scores are converted to normalised scaled scores (mean [M] = 10, standard deviation [SD] = 3). It gives an IQ standard score (M = 100; SD = 15).
Identification of prodromal Alzheimer's disease markers using brain imaging [2 years]
Whole brain volumetry calculation, hippocampus volume calculation, white matter lesions volumetry calculation
Identification of prodromal Alzheimer's disease markers using dosage (pg/mL) of biomarkers in cerebrospinal fluid [2 years]
1-40 beta-amyloid, 1-42 beta-amyloid, tau, phosphorylated tau
Number of adverse event and serious adverse events related to trial procedures [2 years]
Adverse events graded 3-4-5 according to CTCAE v5.0
Evaluation of survival assessed by vital status [2 years]
Date and cause of death

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female 35 years old and over ;
Clinical diagnosis of Down syndrome ;
Patient attending the geriatric outpatient clinic
Patient without diagnosis of Alzheimer's disease;
Patient covered by social welfare;
Patient himself or legal guardian/representative willing and consenting to participate to the study by giving written informed consent;
Patients must have a parent, or / and other reliable caregiver who agrees to accompany him/her to all visits, provide information about the patient as required by the protocol. The parent or caregiver must be a constant and reliable informant with sufficient contact with the patient to have detailed knowledge of the patient's adaptive functioning in order to be able to complete the assessments accurately.

Exclusion Criteria:

Patient presenting a contraindication to MRI in particular carrier of metal implants such as pacemakers;
Patient presenting a serious, severe or unstable pathology (left to the investigator's discretion) whose nature may interfere with the evaluation parameters;
Patient without Alzheimer's disease diagnosis but with severe dementia;
Participation in other clinical trials in the last 3 months prior to the study;
Pregnant woman.