Exploring Sympathetic Nervous System Function in Individuals With Down Syndrome

NCT07238465 | Recruiting Phase 3

• 2 other identifiers: 25-0503T32AG000279
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Down Syndrome; Autonomic Dysfunction

Keywords

Cold Stress; Pain Responses; Fear; Exercise; Blood Pressure; Heart Rate; Caffeine; 12-Hour Fast; Catecholamines; Epinephrine; Norepinephrine; Dopamine

Outcome Measures

Primary Outcomes (43)

• 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 six 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 blood draw, prior to stressors

• 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

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

• Baseline Standing 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 six 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 blood draws, prior to fear simulation

• First Fear Simulation, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  During the first virtual reality fear stressor, around 5 minutes

• Second Fear Simulation, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  During the second fear simulation, around 15 minutes into the test

• First Minute of Pain Patch, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will take place within 1-minute of the application of the pain patch.

• 15 Minutes into Pain Patch Application, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will occur about 15 minutes after the application of the pain patch.

• 12-Hour Fast, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will occur following a 12-hour fast inducing hypoglycemia

• Seated Baseline Blood Draw, 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will occur prior to ingestion of caffeine pill

• 30 Minutes Following Ingestion of Caffeine Pill(s), 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will occur around 30 minutes following participant ingestion of caffeine pill(s)

• 60 Minutes Following Ingestion of Caffeine Pill(s), 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  Blood draw will occur around 60 minutes following participant ingestion of caffeine pill(s)

• Baseline Standing Concentration of Plasma Catecholamines 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 six 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 blood draw, prior to maximal exercise test

• Standing Concentration of Plasma Catecholamines at End of 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 six stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome.

  This blood draw will occur at the very end or immediately following the maximal exercise test on the treadmill

• Seated Baseline Heart Rate, Prior to Cold Pressor Test

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during (in some stressors), and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting seated baseline, prior to cold pressor test, up to or around 5 minutes

• Heart Rate Collected During Cold Pressor Test

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Collected throughout the Cold Pressor Test, around 6 minutes in total

• Standing Baseline Heart Rate, Prior to Fear Simulations

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Standing baseline, prior to fear simulations, up to or around 5 minutes

• Heart Rate, First Fear Simulation

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate will be collected during the first fear simulation, which will last around or up to 10 minutes

• Heart Rate, First Calming Simulation

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate will be recorded during the first calming simulation, which will follow the first fear simulation and will last up to or around 10 minutes.

• Heart Rate, Second Fear Simulation

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate will be recorded during the second fear simulation, which will follow the first calming simulation and will last up to or around 10 minutes.

• Heart Rate, Second Calming Simulation

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate will be recorded during the second calming simulation, which will follow the second fear simulation and will last up to or around 10 minutes.

• Heart Rate, Baseline Prior to Pain Patch

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Baseline seated heart rate recordings will occur prior to application of pain patch, up to or around 5 minutes

• Heart Rate, During Pain Patch

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate will be recorded following the application of the capsaicin pain patch, up to or around 15 minutes

• Heart Rate, Baseline 12-Hour Fast

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting baseline will be recorded prior (and on a separate day from) the 12-hour fast, up to or around 5 minutes.

• Heart Rate, 12-Hour Fast

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six 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 heart rate recordings will occur following a 12-hour fast, up to or around 15 minutes.

• Heart Rate, Seated Baseline, Caffeine Consumption

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting baseline heart rate will be recording prior to caffeine consumption, up to or around 5 minutes

• Heart Rate, Following Caffeine Consumption

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate recordings will occur immediately following caffeine consumption, up to or around 60 minutes.

• Heart Rate, Baseline Prior to Maximal Exercise Test

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Baseline heart rate recordings will occur prior to the maximal exercise test, up to or around 5 minutes.

• Heart Rate, Maximal Exercise Test

  Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous heart rate recordings will take place throughout the maximal aerobic exercise test on the treadmill, up to or around 20 minutes

• Seated Baseline Blood Pressure, Prior to Cold Pressor Test

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting seated baseline, prior to cold pressor test, up to or around 5 minutes

• Blood Pressure Collected During Cold Pressor Test

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Collected throughout the Cold Pressor Test, around 6 minutes in total

• Standing Baseline Blood Pressure, Prior to Fear Simulations

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Standing baseline, prior to fear simulations, up to or around 5 minutes

• Blood Pressure, First Fear Simulation

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure will be recorded during the first fear simulation, which will last up to or around 10 minutes.

• Blood Pressure, First Calming Simulation

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure will be recorded during the first calming simulation, which will follow the first fear simulation and will last up to or around 10 minutes.

• Blood Pressure, Second Fear Simulation

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure will be recorded during the second fear simulation, which will follow the first calming simulation and will last up to or around 10 minutes.

• Blood Pressure, Second Calming Simulation

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure will be recorded during the second calming simulation, which will follow the second fear simulation and will last up to or around 10 minutes.

• Blood Pressure, Baseline Prior to Pain Patch

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Baseline seated blood pressure recordings will occur prior to application of pain patch, up to or around 5 minutes

• Blood Pressure, During Pain Patch

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure will be recorded following the application of the capsaicin pain patch, up to or around 15 minutes

• Blood Pressure, Baseline 12-Hour Fast

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting baseline will be recorded prior (and on a separate day from) the 12-hour fast, up to or around 5 minutes.

• Blood Pressure, 12-Hour Fast

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six 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 blood pressure recordings will occur following a 12-hour fast, up to or around 15 minutes.

• Blood Pressure, Seated Baseline, Caffeine Consumption

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Resting baseline blood pressure will be recording prior to caffeine consumption, up to or around 5 minutes

• Blood Pressure, Following Caffeine Consumption

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure recordings will occur immediately following caffeine consumption, up to or around 60 minutes.

• Blood Pressure, Baseline Prior to Maximal Exercise Test

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Baseline blood pressure recordings will occur prior to the maximal exercise test, up to or around 5 minutes.

• Blood Pressure, Maximal Exercise Test

  Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the six stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome.

  Continuous blood pressure recordings will take place throughout the maximal aerobic exercise test on the treadmill, up to or around 20 minutes

Secondary Outcomes (9)

• Facial Affective Scale Score, Baseline Assessment

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

• Facial Affective Scale Score, Cold Pressor Test, 1.5 Minutes

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

• Facial Affective Scale Score, Cold Pressor Test, Finale

  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

• Facial Affective Scale Score, During Pain Response, 1-Minute

  Assessment will take place approximately 1-minute following administration of the pain patch

• Facial Affective Scale Score, Pain Response, 5 Minutes

  Up to or around 5 minutes into pain patch

Study Arms (2)

Individuals with Down syndrome

EXPERIMENTAL

The investigators will be recruiting participants between the ages of 18-50 for the study investigating responses to six sympathetic stressors compared to age and sex matched individuals without Down syndrome.

Other: Fear Response; Other: Cold Stress; Other: Pain Response; Other: Caffeine; Other: 12-Hour Fast; Other: Maximal Dynamic Exercise

Individuals without Down syndrome

EXPERIMENTAL

The investigators will be recruiting individuals without Down syndrome between the ages of 18-50 to serve as the comparisons for individuals with Down syndrome across the six sympathetic stressors.

Other: Fear Response; Other: Cold Stress; Other: Pain Response; Other: Caffeine; Other: 12-Hour Fast; Other: Maximal Dynamic Exercise

Interventions

Fear Response OTHER

Fear 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 the cardiovascular physiology of how individuals with DS will respond during a scary simulation. The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during a fear simulation using virtual reality goggles 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.

Also known as: Physiological Fear Response, Virtual Reality Simulation

Individuals with Down syndrome; Individuals without Down syndrome

Cold Stress OTHER

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.

Also known as: Cold Pressor Test, Cold Water

Individuals with Down syndrome; Individuals without Down syndrome

Pain Response OTHER

Pain triggers the sympathetic nervous system, known as the 'fight-or-flight' response, which prepares the body to respond to the perceived threat (i.e., hurt) by increasing heart rate, blood pressure, and releasing catecholamines. These measurements will be taken to examine how individuals with DS will respond during application of a painful patch. The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed during application of a pain patch in individuals with Down syndrome, who have proposed autonomic dysfunction. This pain patch is similar to what someone would buy at the drug store for sore muscles. This study will compare responses among individuals with Down syndrome to a control group without Down syndrome.

Also known as: Capsaicin Patch

Individuals with Down syndrome; Individuals without Down syndrome

Caffeine OTHER

Caffeine acts as a stimulant to the sympathetic nervous system leading to an increase in blood pressure, heart rate, and release of catecholamines. The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed following ingestion of a caffeine pill (similar to \~2 cups of coffee) 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.

Also known as: Caffeine Pill, Coffee

Individuals with Down syndrome; Individuals without Down syndrome

12-Hour Fast OTHER

Fasting-induced hypoglycemia triggers a 'fight-or-flight' response as the body attempts to raise low blood glucose levels to bring them back to 'normal'. These measurements will be taken to examine how individuals with DS will respond following a 12-hour abstinence from food, inducing low blood sugar. The investigators are looking at how plasma catecholamines (i.e., Epinephrine, Norepinephrine, and Dopamine), blood pressure, and heart rate are expressed following a 12-hour fast 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.

Also known as: Low Blood Sugar, Hypoglycemia

Individuals with Down syndrome; Individuals without Down syndrome

Maximal Dynamic Exercise OTHER

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.

Also known as: VO2peak, Treadmill Exercise

Individuals with Down syndrome; Individuals without Down syndrome

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator
• Linda Crnic Institute for Down Syndrome: collaborator
• GLOBAL Down Syndrome Foundation: collaborator
• University of Colorado Colorado Clinical and Translational Sciences Institute: collaborator

Study Sites (1)

Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Down Syndrome; Primary Dysautonomias; Motor Activity

Interventions

Cold-Shock Response; Caffeine; Coffee; Hig1 protein, mouse

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Autonomic Nervous System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Stress, Physiological; Physiological Phenomena; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Food and Beverages

Central Study Contacts

Sara R Sherman, PhD

CONTACT

303-724-0598; sara.r.sherman@cuanschutz.edu

Constance Brecl

CONTACT

constance.brecl@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2025
• First Posted: November 20, 2025
• Study Start: April 6, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)