Down Syndrome Clinical Trials - Study of Alzheimer's Disease in Down Syndrome (LIFE-DSR)

The Down Syndrome Clinical Trials Network (DS-CTN) Study of Alzheimer's Disease in Down Syndrome

The primary objective is to characterize trajectories of change on the primary outcome measures in this study population through longitudinal collection of measures of cognition, function, behavior, and health status.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer's Disease in Down Syndrome

Detailed Description

The DS-CTN will engage in rigorous, high quality research to better understand AD-DS and the medical needs of this population. The LIFE-DSR study will utilize the DS-CTN network to achieve these goals through evidence-based research and a combination of proven and novel methodologies. The network will initially recruit and employ experts and clinical trial sites who have access to adults with DS and whose focus is on AD-DS.

This trial also aims to develop sensitive and well-validated assessment instruments of cognition, behavior and function appropriate for future clinical trials directed at AD-DS in adults with DS ages 25 and older.

In addition, this LIFE-DSR study will serve as a parent protocol that includes one or more sub-studies, each of which has its own protocol and consent form. These sub-studies will recruit from eligible participants enrolled in this LIFE-DSR protocol.

• Study Type: Observational
• Enrollment (Actual): 252

Contacts and Locations

• Study Contact: Name: Tashia Harris, MS; Phone Number: 781-825-1279; Email: tharris@lumindidsc.org
• Study Contact Backup: Name: Lois Kelly; Phone Number: 7818251262; Email: lkelly@lumindidsc.org

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
  • California
    • Irvine, California, United States, 92697
      • University California Irvine
    • La Jolla, California, United States, 92093
      • University of California, San Diego
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Park Ridge, Illinois, United States, 60068
      • Advocate Health
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Kansas University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 044106
      • Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Males and females, aged 25 and older, with a diagnosis of DS, typically supported by karyotype analysis documenting full trisomy for chromosome 21 or complete unbalanced translocation of chromosome 21.

Description

Inclusion Criteria:

1. Age 25 years or older
2. Diagnosis of DS, typically supported by karyotype analysis documenting full trisomy for chromosome 21 or complete unbalanced translocation of chromosome 21. Karyotype analysis is not required for study entry
3. Participants, or Legal Authorized Representative, and their study partner if applicable, in the opinion of the investigator, are able to understand and willing to sign written informed consent.
4. Participants must have a study partner who has frequent interaction with the participant on a regular basis, will agree to participate in annual clinic visits, can provide accurate responses to questions about the participant, and facilitate participation in the study visits, in the opinion of site PI or study coordinator.
5. Participant and study partner must be capable of reliably completing study assessments.

Exclusion Criteria Participants and study partners who, in the opinion of the site PI, are not able to complete trial procedures or adhere to the schedule of study assessments will be excluded from study participation.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Measure	Severe Impairment Battery (SIB) with Shoebox Test. If the participant achieves a score 60 or above on the SIB, the Down Syndrome Mental Status Examination (DS-MSE) will also be administered. Subscale Ranges: Social Interaction - 0 - 6 Orientation - 0 - 8 Visuospatial Ability - 0 - 8 Construction - 0 - 12 Language - 0 - 56 Memory - 0 - 16 Praxis - 0 - 8 Attention - 0 - 15 Orienting to name - 0 - 4 Higher scores reflect better performance for each subscale. Scores above 60 mean the participant completes the Shoebox Memory Test.	through study completion, an average of 2 years
Functional Measure	The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) Vineland-3 is an adaptive behavior measure used to assess intellectual/developmental/other disabilities. Total score range: 0 - 140 Expressive Communication: 0 - 98 49 questions - range: 0 - 2 per Q Written Communication: 0 - 76 38 questions - range: 0 - 2 per Q Personal Daily Living Skills - 0 - 110 55 questions - range: 0 - 2 per Q	through study completion, an average of 2 years
Behavioral Measure	Dementia Questionnaire for People with Learning Disabilities (DLD) - Measures specific cognitive and functional deterioration as a result of dementia, and functional deterioration as a result of severe sensory or psychiatric problems. Range of total possible scores: 0 - 100 50 Questions with a possible range of 0 - 2 per question. Higher scores reflect worse performance. Score Calculation: Categories are mixed throughout the questionnaire. To calculate the score at the end, scores on each page are added up and categorizes into Cognitive Scores, or SCS (categories 1 - 3: Short-term memory, Long-term memory, and Spatial & Temporal Orientation) and Social Scores, or SOS (Categories 4 - 8: Speech, Practical Skills, Mood, Activity & Interest, Behavioral Disturbance).	through study completion, an average of 2 years
Health Measures	New-onset seizures or significantly increased frequency of seizures	through study completion, an average of 2 years
Behavioral Measure	Neuropsychiatric Inventory (NPI) - Neuropsychiatric Inventory (NPI) evaluates both the frequency and severity of 10 neuropsychiatric features, including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability and lability, and aberrant motor behavior, as well as evaluates sleep and appetite/eating disorders. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously). Severity assessments range from 1 (mild) to 3 (severe). The score for each subscale is the product of severity and frequency and the total score is the sum of all subscales.	through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome Measure Preliminary composite measure from the scales being used in LIFE-DSR	To derive a preliminary composite measure from the scales being used in LIFE-DSR that is most sensitive to change in this population and which can be validated in a future prospective study. If the participant achieves a score 60 or above on the SIB, the Down Syndrome Mental Status Examination (DS-MSE) will also be administered. The maximum score is 100.	through study completion, an average of 2 years
Exploratory Outcome Measure Novel multi-domain instrument for AD-DS development	To integrate and further validate a novel and highly sensitive multidomain instrument for AD-DS upon its completion (Professor A. Strydom, Kings College, London). This instrument is being developed under a separate protocol and upon its validation will be integrated into LIFE-DSR to evaluate its responsiveness to change in clinically important domains.	through study completion, an average of 2 years
Exploratory Outcome Measure Potential Screening Measures	Individual subscales from the larger test batteries included in the LIFE-DSR Primary Outcome Measures, Severe Impairment Battery (SIB) with Shoebox Test, the Down Syndrome Mental Status Examination (DS-MSE), NPI, and Vineland3. These could then be further validated in a future prospective study. SIB - Social Interaction - 0 - 6 Orientation - 0 - 8 Visuospatial Ability - 0 - 8 Construction - 0 - 12 Language - 0 - 56 Memory - 0 - 16 Praxis - 0 - 8 Attention - 0 - 15 Orienting to name - 0 - 4 Scores above 60 mean the participant completes the Shoebox Memory Test. Vineland-3 -Total score range: 0 - 140 DLD - Questions with a possible range of 0 - 2 per question. Higher scores reflect worse performance. NPI - The score for each subscale is the product of severity and frequency and the total score is the sum of all subscales.	through study completion, an average of 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Outcome Measure Obtain and bank plasma sample for future development translational biomarkers	The biomarkers are those such as those related to amyloid or tau, Nfl, gene expression, genotype (including ApoE), that may be useful for trial enrichment and to provide evidence of target engagement and pharmacodynamic, as well as biologic, effects.	through study completion, an average of 2 years
Exploratory Outcome Measure	To derive potential screening measures, from the larger test batteries, that might be best used for screening of significant AD dementia risk. These could then be further validated in a future prospective study.	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: LuMind IDSC Foundation
• Collaborators: Alzheimer's Disease Cooperative Study (ADCS)
• Investigators: Study Director: Lois Kelly, LuMind IDSC Foundation

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2019
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Down Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Intellectual Disability; Dementia; Tauopathies; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Alzheimer Disease; Down Syndrome
• Other Study ID Numbers: ADC-059-LIFE-DSR

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