GO-DS21: Elucidating Age-related Comorbidity Patterns in Down Syndrome (DS)

Sponsor

King's College London (Other)

Overall Status

Recruiting

CT.gov ID

NCT05310552

Collaborator

Fondation Jérôme Lejeune (Other), Parc de Salut Mar (Other)

300

Enrollment

Locations

48.7

Anticipated Duration (Months)

100

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a non-drug, multicenter, prospective cohort study. It will be conducted in 300 volunteers from 12 to 45 years of age (inclusive) with a diagnosis of Down syndrome from 3 countries (France, Spain, United Kingdom (UK)). The basic hypotheses of the study are the following:

Diseases (and comorbidity) arise from one or more biological networks perturbed by the genetic disorder (trisomy 21) through interaction with environmental risks factors and epigenetic changes.
Health comorbidity patterns in DS individuals (particularly of obesity and related conditions) will likely vary by age and sex.
Obesity comorbidity patterns will relate to variation in factors including lifestyle, stress-response, severity of intellectual disability (ID) and variation in cognitive domains such as executive functioning.
Stress responses, as measured with cortisol concentrations, will differentiate individuals with DS who are obese and those who are not. Extremes in phenotype (Obese vs. Non-obese) will be related to differences in the metabolomic, transcriptomic, and microbiome concentrations.

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome	Other: No interventions - observational study

Detailed Description

The study will be conducted in n= 300 volunteers with DS from 3 countries (France, Spain, UK); equal numbers in 3 age groups (12 - 18 years; 19 - 34 years; 35 - 45 years). The total number of volunteers expected to be included in each country is n = 100.

From the initial cross-sectional cohort, individuals will be selected on the basis of obesity status and invited to participate in a nested case-control study (n = 30 for normal weight DS individuals and n = 30 DS individuals with extreme phenotype). In adults, normal weight is defined as BMI 18.5 to 24.9 and significant obesity as BMI > 35 kg/m2. In children under age 18, the research team will use the International Obesity Task Force (IOTF) curves which are international norms) with IOTF > 30 for obese and IOTF 18.5 - 25 for the normal weight group. The research team will monitor allocation using monthly eCRF recruitment reports for central allocation of recruits to ensure balance between age, sex and BMI between the "cases" and the "controls".

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Elucidating Age-related Comorbidity Patterns in Down Syndrome (DS): Prospective Cohort (GO-DS21 Cohort Study)

Actual Study Start Date :

Jun 10, 2021

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2025

Outcome Measures

Primary Outcome Measures

Body Mass Index [1 year]
Height and weight measurements will be aggregated to arrive at one reported value: Body Mass Index (BMI), in kg/m^2
Food Frequency Questionnaire [1 year]
Average daily nutrient intake
Short Minnesota Leisure Time Physical Activity Questionnaire [1 year]
Energy expenditure in 14 days
Mental health questionnaire [1 year]
Reiss Screen for Maladaptive Behaviour - composite outcome measure consisting of the following multiple sub-measures: Aggressive behavior Autism Psychosis Paranoia Depression (behavioural signs) Depression (physical signs) Dependent personality disorder Avoidant disorder

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 45 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

Males and females aged 12 to 45 years
With established genetic diagnosis of Down syndrome (full trisomy 21; based on karyotype results - not exclusion if not available but will need to confirm karyotype if not done previously)
Availability of parent/caregiver to accompany the subject to clinical visits and to be willing to give written informed consent, when necessary

Exclusion Criteria:

Confirmed mosaic trisomy 21, partial trisomy 21, or translocation
Comorbid conditions - Participation is allowed as long as the condition(s) are considered stable and it do not interfere with the participation of the study
Subjects with evidence of dementia or meeting clinical diagnoses for dementia
Participation in a medication treatment trial in the last 3 months prior to the study

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institute Jérôme Lejeune	Paris	France	75015
2	Institut Hospital del Mar d'Investigacions Mèdiques	Barcelona	Spain	08003
3	King's College London	London	United Kingdom	SE5 8AB