NCT07238465 · University of Colorado, Denver
Exploring Sympathetic Nervous System Function in Individuals With Down Syndrome
(DIVE)
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
Cold Stress
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.
OTHER
Maximal Dynamic Exercise
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.
OTHER
Isometric Handgrip Exercise with Post-Exercise Muscle Ischemia
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.
OTHER
Head-up Tilt Table Test
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.
Primary outcome measures
Seated Baseline Concentration of Plasma Catecholamines
Time frame: Seated baseline blood draw, prior to stressors
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.
Standing Baseline Concentration of Plasma Catecholamines
Time frame: Blood draw will occur in standing position, prior to head up tilt table testing
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.
Concentration of Plasma Catecholamines During Cold Pressor Test
Time frame: During the cold stress test, around or up to 5 minutes
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.
Concentration of Plasma Catecholamines During Handgrip Test
Time frame: Blood draws occur around or up to 2-3 minutes into 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.
Concentration of Plasma Catecholamines During Post Exercise Muscle Ischemia
Time frame: Seated blood draw to occur, around or about 2-3 minutes into post exercise muscle ischemia
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.
Supine Concentration of Plasma Catecholamines
Time frame: Blood draws during or around 10 minutes of supine rest
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.
Supine Concentration of Plasma Catecholamines, 5 Minutes into Head-Up Tilt
Time frame: At or around 5 minutes into the head-up tilt table stimulus
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.
Supine Concentration of Plasma Catecholamines, 10 Minutes into Head-Up Tilt
Time frame: At or around 10 minutes into the head-up tilt table stimulus
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.
Baseline Standing Concentration of Plasma Catecholamines Prior to Maximal Exercise Test
Time frame: Standing baseline blood draw, prior to maximal exercise 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.
Standing Concentration of Plasma Catecholamines at End of Maximal Exercise Test
Time frame: This blood draw will occur at the very end or immediately following the maximal exercise test on the treadmill
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.
Standing Concentration of Plasma Catecholamines, 30 Minutes Post Maximal Exercise
Time frame: This blood draw will occur around 30 minutes following the maximal exercise test on the treadmill
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.
Standing Concentration of Plasma Catecholamines, 60 Minutes Post Maximal Exercise
Time frame: This blood draw will occur at the around 60 minutes following the maximal exercise test on the treadmill
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.
Seated Baseline Heart Rate, Prior to Cold Pressor Test
Time frame: Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
Investigators will collect beat-to-beat heart rate recordings in all participants before, during (in some stressors), and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Heart Rate Collected During Cold Pressor Test
Time frame: Collected throughout the Cold Pressor Test, around 6 minutes in total
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Heart Rate, Maximal Exercise Test
Time frame: Continuous heart rate recordings will take place throughout the maximal aerobic exercise test on the treadmill, up to or around 20 minutes
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Seated Baseline Blood Pressure, Prior to Cold Pressor Test
Time frame: Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Blood Pressure Collected During Cold Pressor Test
Time frame: Collected throughout the Cold Pressor Test, around 6 minutes in total
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Heart Rate Collected During Handgrip with Post-Exercise Muscle Ischemia
Time frame: Collected throughout the Handgrip tests with Post-Exercise Muscle Ischemia, around 12 minutes in total
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Heart Rate Collected During Head-Up Tilt Table Test
Time frame: Collected throughout the Head-Up Tilt Table Test, around 25 minutes in total
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Blood Pressure Collected During Handgrip Test with Post-Exercise Muscle Ischemia
Time frame: Collected throughout the handgrip test with post-exercise muscle ischemia, up to or around 12 minutes
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Blood Pressure Collected During Head-Up Tilt Table Test
Time frame: Collected throughout the head-up tilt table test, around 25 minutes in total
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
- Euthyroid or on stable thyroid medication dose for at least 6 months
- Free from cardiovascular, pulmonary, inflammatory, or metabolic disease in the past 6 months that would prevent participation in study procedures
- BMI \<45kg/m2
- Ability to tolerate repeated blood draws / catheter placement
Exclusion criteria
- 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
- Self-reported diabetes or use of glucose-lowering medication
- Tobacco products, including vaping, or marijuana use
- Currently pregnant
- Post-menopausal women Specific Exclusion Criteria for Certain Stressors:
- Orthopedic limitations that would prohibit exercise or movement for exercise
- Fracture of limb to be immersed for CPT
- Open cut or sore on hand to be immersed for CPT
- Raynaud's syndrome for CPT
- Chronic caffeine drinkers for caffeine stressor (consumption of caffeine in the last 7 days)
Where
- Aurora, Colorado
Collaborators
National Institute on Aging (NIA), Linda Crnic Institute for Down Syndrome, GLOBAL Down Syndrome Foundation, University of Colorado Colorado Clinical and Translational Sciences Institute
Related conditions & keywords
Frequently asked questions
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Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
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Data: ClinicalTrials.gov · synced Oct 13, 2026 · Source of record for eligibility and locations