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

Primary Purpose

Down Syndrome, Alzheimer Disease

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Neuro-imaging, Lumbar puncture

About this trial

This is an interventional diagnostic trial for Down Syndrome focused on measuring Down Syndrome, Alzheimer Disease, Marker, Neuropsychological, Prodromal, Risk factors

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Institut Jérôme LejeuneRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Down syndrome patients

Arm Description

Outcomes

Primary Outcome Measures

Age of onset of Alzheimer's disease

age (year)

Gender that could influence the age of onset of the disease as determined by medical record review

Level of intellectual diasability that could influence the age of onset of the disease as determined by medical record review

Family history of Alzheimer's disease that could influence the age of onset of the disease as determined by medical record review

Cardio-vascular risk factors that could influence the age of onset of the disease as determined by medical record review

Down syndrome comorbidies that could influence the age of onset of the disease as determined by medical record review

Genetic's factor other than APP that could influence the age of onset of the disease as determined by medical record review

Head trauma that could influence the age of onset of the disease as determined by medical record review

Age of menopause that could influence the age of onset of the disease as determined by medical record review

Secondary Outcome Measures

Evaluation of neuropsychological evolution using Katz Index of Independence in Activities of Daily Living (Katz ADL) score

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)

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

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

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

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

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

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

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

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

1-40 beta-amyloid, 1-42 beta-amyloid, tau, phosphorylated tau

Number of adverse event and serious adverse events related to trial procedures

Adverse events graded 3-4-5 according to CTCAE v5.0

Evaluation of survival assessed by vital status

Date and cause of death

Full Information

NCT ID

NCT03901261

First Posted

February 4, 2019

Last Updated

February 7, 2023

Sponsor

Institut Jerome Lejeune

1. Study Identification

Unique Protocol Identification Number

NCT03901261

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 26, 2019 (Actual)

Primary Completion Date

March 31, 2023 (Anticipated)

Study Completion Date

March 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut Jerome Lejeune

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Down Syndrome, Alzheimer Disease

Keywords

Down Syndrome, Alzheimer Disease, Marker, Neuropsychological, Prodromal, Risk factors

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Interventional prospective monocentric, national open study with single arm

Masking

None (Open Label)

Allocation

N/A

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Down syndrome patients

Arm Type

Experimental

Intervention Type

Procedure

Intervention Name(s)

Neuro-imaging, Lumbar puncture

Intervention Description

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

Primary Outcome Measure Information:

Title

Age of onset of Alzheimer's disease

Description

age (year)

Time Frame

2 years

Title

Gender that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Level of intellectual diasability that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Family history of Alzheimer's disease that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Cardio-vascular risk factors that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Down syndrome comorbidies that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Genetic's factor other than APP that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Head trauma that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Title

Age of menopause that could influence the age of onset of the disease as determined by medical record review

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Evaluation of neuropsychological evolution using Katz Index of Independence in Activities of Daily Living (Katz ADL) score

Description

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Lawton-Brody Instrumental Activities of Daily Living scale ( IADL)

Description

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) score

Description

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities score

Description

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.

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Cambridge Cognition Examination score

Description

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Cued Recall test score

Description

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Cancellation task

Description

Measure of task accuracy (total number of correct responses, range score 0-16) and total time performance (in seconds) were included in the analyses.

Time Frame

2 years

Title

Evaluation of neuropsychological evolution using Leiter III assessment score

Description

Time Frame

2 years

Title

Identification of prodromal Alzheimer's disease markers using brain imaging

Description

Whole brain volumetry calculation, hippocampus volume calculation, white matter lesions volumetry calculation

Time Frame

2 years

Title

Identification of prodromal Alzheimer's disease markers using dosage (pg/mL) of biomarkers in cerebrospinal fluid

Description

1-40 beta-amyloid, 1-42 beta-amyloid, tau, phosphorylated tau

Time Frame

2 years

Title

Number of adverse event and serious adverse events related to trial procedures

Description

Adverse events graded 3-4-5 according to CTCAE v5.0

Time Frame

2 years

Title

Evaluation of survival assessed by vital status

Description

Date and cause of death

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anne-Sophie REBILLAT, MD, PhD

Phone

+33 1 56 58 63 00

annesophie.rebillat@institutlejeune.org

Facility Information:

Facility Name

Institut Jérôme Lejeune

City

Paris

ZIP/Postal Code

75015

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anne-Sophie REBILLAT, MD, PhD

Phone

+33 1 56 58 63 00

annesophie.rebillat@institutlejeune.org

First Name & Middle Initial & Last Name & Degree

Anne-Sophie REBILLAT, MD

First Name & Middle Initial & Last Name & Degree

Anne HIANCE-DELAHAYE, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

29226868

Citation

Sinai A, Mokrysz C, Bernal J, Bohnen I, Bonell S, Courtenay K, Dodd K, Gazizova D, Hassiotis A, Hillier R, McBrien J, McCarthy J, Mukherji K, Naeem A, Perez-Achiaga N, Rantell K, Sharma V, Thomas D, Walker Z, Whitham S, Strydom A. Predictors of Age of Diagnosis and Survival of Alzheimer's Disease in Down Syndrome. J Alzheimers Dis. 2018;61(2):717-728. doi: 10.3233/JAD-170624.

Results Reference

background

PubMed Identifier

28664561

Citation

McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2017 Sep;61(9):843-852. doi: 10.1111/jir.12390. Epub 2017 Jun 29.

Results Reference

background

PubMed Identifier

2971602

Citation

Mann DM. Alzheimer's disease and Down's syndrome. Histopathology. 1988 Aug;13(2):125-37. doi: 10.1111/j.1365-2559.1988.tb02018.x.

Results Reference

background

PubMed Identifier

16961706

Citation

Coppus A, Evenhuis H, Verberne GJ, Visser F, van Gool P, Eikelenboom P, van Duijin C. Dementia and mortality in persons with Down's syndrome. J Intellect Disabil Res. 2006 Oct;50(Pt 10):768-77. doi: 10.1111/j.1365-2788.2006.00842.x.

Results Reference

background

PubMed Identifier

28289920

Citation

Lautarescu BA, Holland AJ, Zaman SH. The Early Presentation of Dementia in People with Down Syndrome: a Systematic Review of Longitudinal Studies. Neuropsychol Rev. 2017 Mar;27(1):31-45. doi: 10.1007/s11065-017-9341-9. Epub 2017 Mar 13.

Results Reference

background

PubMed Identifier

29159043

Citation

Neale N, Padilla C, Fonseca LM, Holland T, Zaman S. Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome. Neuroimage Clin. 2017 Nov 6;17:263-271. doi: 10.1016/j.nicl.2017.10.022. eCollection 2018.

Results Reference

background

PubMed Identifier

20807454

Citation

Vemuri P, Jack CR Jr. Role of structural MRI in Alzheimer's disease. Alzheimers Res Ther. 2010 Aug 31;2(4):23. doi: 10.1186/alzrt47.

Results Reference

background

PubMed Identifier

25511894

Citation

Lleo A, Cavedo E, Parnetti L, Vanderstichele H, Herukka SK, Andreasen N, Ghidoni R, Lewczuk P, Jeromin A, Winblad B, Tsolaki M, Mroczko B, Visser PJ, Santana I, Svenningsson P, Blennow K, Aarsland D, Molinuevo JL, Zetterberg H, Mollenhauer B. Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases. Nat Rev Neurol. 2015 Jan;11(1):41-55. doi: 10.1038/nrneurol.2014.232. Epub 2014 Dec 16.

Results Reference

background

PubMed Identifier

10331678

Citation

Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology. 1999 May 12;52(8):1555-62. doi: 10.1212/wnl.52.8.1555.

Results Reference

background

PubMed Identifier

14044222

Citation

KATZ S, FORD AB, MOSKOWITZ RW, JACKSON BA, JAFFE MW. STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. JAMA. 1963 Sep 21;185:914-9. doi: 10.1001/jama.1963.03060120024016. No abstract available.

Results Reference

background

PubMed Identifier

5349366

Citation

Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969 Autumn;9(3):179-86. No abstract available.

Results Reference

background

PubMed Identifier

17470960

Citation

Deb S, Hare M, Prior L, Bhaumik S. Dementia screening questionnaire for individuals with intellectual disabilities. Br J Psychiatry. 2007 May;190:440-4. doi: 10.1192/bjp.bp.106.024984.

Results Reference

background

PubMed Identifier

15312062

Citation

Ball SL, Holland AJ, Huppert FA, Treppner P, Watson P, Hon J. The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome. J Intellect Disabil Res. 2004 Sep;48(Pt 6):611-20. doi: 10.1111/j.1365-2788.2004.00630.x.

Results Reference

background

PubMed Identifier

19679070

Citation

Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron. 2009 Aug 13;63(3):287-303. doi: 10.1016/j.neuron.2009.06.026.

Results Reference

background

PubMed Identifier

27858714

Citation

Carmona-Iragui M, Santos T, Videla S, Fernandez S, Benejam B, Videla L, Alcolea D, Blennow K, Blesa R, Lleo A, Fortea J. Feasibility of Lumbar Puncture in the Study of Cerebrospinal Fluid Biomarkers for Alzheimer's Disease in Subjects with Down Syndrome. J Alzheimers Dis. 2017;55(4):1489-1496. doi: 10.3233/JAD-160827.

Results Reference

background

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

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