About this trial

Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with widespread organ dysfunction, including abnormalities in the autonomic nervous system (ANS). The ANS regulates critical functions such as heart rate (HR) and blood pressure (BP), both essential for maintaining homeostasis and supporting physical activity. Individuals with DS often exhibit blunted HR responses to exercise-typically \~30 beats per minute below expected levels-suggesting reduced sympathetic nervous system (SNS) activity. The SNS governs rapid changes in HR and BP during stress by releasing catecholamines: epinephrine (from the adrenal medulla) and norepinephrine (from sympathetic nerve endings). Despite its importance, SNS function has not been comprehensively assessed among individuals with DS.

This study addresses a critical knowledge gap by evaluating SNS responses to physiological stressors in individuals with DS. The investigators will measure beat-to-beat HR and BP, along with plasma catecholamine levels, in response to sympathetic activation, comparing individuals with DS to age- and sex-matched controls. Understanding the mechanisms of SNS dysfunction in DS is vital, as it likely underlies reduced exercise capacity and contributes to broader clinical challenges. These insights may guide targeted interventions to improve cardiovascular function, physical capacity, and overall quality of life in this understudied population.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

18-50 yrs old and apparently healthy individuals

Ability to understand the study and give assent to participate

Has a study partner who can attend all visits for the individuals with DS, and answer questionnaires, provide consent when necessary

Corrected or non-existent congenital heart disease

Disqualifiers

Hypertension (resting systolic blood pressure [SBP] ≥140 and/or diastolic blood pressure [DBP] ≥90 mmHg) this includes those on medications to treat hypertension

Hypotension (resting BP of <90/60 mmHg)

Cancer in the last six months

Any heart-rate-altering medications or any other medication that may modify metabolic responses

Trial design

Design model

Parallel

Treatments tested in this trial

Cold Stress
Other intervention
Cold triggers the sympathetic nervous system, known as the 'fight-or-flight' response, which prepares the body to respond to a perceived threat by increasing heart rate, blood pressure, and releasing catecholamines. These measurements will be taken to examine how individuals with DS will respond during a cold stress test. The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during a cold stress test in individuals with Down syndrome, who have proposed autonomic dysfunction. This study will compare responses among individuals with Down syndrome to a control group without Down syndrome.
Maximal Dynamic Exercise
Other intervention
The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during a treadmill maximal exercise test in individuals with Down syndrome, who have proposed autonomic dysfunction. This study will compare responses among individuals with Down syndrome to a control group without Down syndrome.
Isometric Handgrip Exercise with Post-Exercise Muscle Ischemia
Other intervention
The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during a isometric handgrip exercise followed by an ischemic period which will be induced by a blood pressure cuff in individuals with Down syndrome, who have proposed autonomic dysfunction. This study will compare responses among individuals with Down syndrome to a control group without Down syndrome.
Head-up Tilt Table Test
Other intervention
The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during passive head-up tilt testing which is a standardized, noninvasive clinical and research procedure used to characterize cardiovascular autonomic responses to orthostatic stress, among individuals with Down syndrome, who have proposed autonomic dysfunction.

Treatment groups

200 Participants

are divided into 2 treatment groups

Group A: Individuals with Down syndromeExperimental treatment 4 interventions

Group B: Individuals without Down syndromeExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Seated Baseline Concentration of Plasma Catecholamines

Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

Time frame

Seated baseline blood draw, prior to stressors

2

Standing Baseline Concentration of Plasma Catecholamines

Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

Time frame

Blood draw will occur in standing position, prior to head up tilt table testing

3

Concentration of Plasma Catecholamines During Cold Pressor Test

Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

Time frame

During the cold stress test, around or up to 5 minutes

4

Concentration of Plasma Catecholamines During Handgrip Test

Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

Time frame

Blood draws occur around or up to 2-3 minutes into handgrip test

Secondary outcomes

1

Facial Affective Scale Score, Baseline Assessment

Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score. This will take up to or around approximately 5 minutes to complete.

Time frame

Baseline Assessment of Facial Affective Scale, this will occur prior to any stressors.

2

Facial Affective Scale Score, Cold Pressor Test, 1.5 Minutes

Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score.

Time frame

Assessment occurs around or up to 90 seconds (1.5 minutes) into cold water immersion

3

Facial Affective Scale Score, Cold Pressor Test, Finale

Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score.

Time frame

Assessment occurs immediately following or during the last minute of the Cold Pressor Test, up to or around 6 minutes following placement of arm into cold

Exploring Sympathetic Nervous System Function in Individuals With Down Syndrome

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

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