Recruiting
Phase 3

SNS Assessment

Sponsor:

University of Colorado, Denver

Code:

NCT07238465

Conditions

Down Syndrome

Autonomic Dysfunction

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Accepted

Interventions

Fear Response

Cold Stress

Pain Response

Caffeine

12-Hour Fast

Study Details

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

Study ID

NCT07238465

Start date

Apr 6, 2026

Status verified date

Apr, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Accepted

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)

Study Design

Enrollment

200 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: Individuals with Down syndrome

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.

experimental: Individuals without Down syndrome

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.

Interventions

Fear Response

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.

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.

Pain Response

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.

Caffeine

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.

12-Hour Fast

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.

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.

Primary outcome measure

  • Seated Baseline Concentration of Plasma Catecholamines [ Time Frame: Seated baseline blood draw, prior to stressors ]
  • Concentration of Plasma Catecholamines During Cold Pressor Test [ Time Frame: During the cold stress test, around or up to 5 minutes ]
  • Baseline Standing Concentration of Plasma Catecholamines [ Time Frame: Standing baseline blood draws, prior to fear simulation ]
  • First Fear Simulation, Concentration of Plasma Catecholamines [ Time Frame: During the first virtual reality fear stressor, around 5 minutes ]
  • Second Fear Simulation, Concentration of Plasma Catecholamines [ Time Frame: During the second fear simulation, around 15 minutes into the test ]
  • First Minute of Pain Patch, Concentration of Plasma Catecholamines [ Time Frame: 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 [ Time Frame: Blood draw will occur about 15 minutes after the application of the pain patch. ]
  • 12-Hour Fast, Concentration of Plasma Catecholamines [ Time Frame: Blood draw will occur following a 12-hour fast inducing hypoglycemia ]
  • Seated Baseline Blood Draw, Concentration of Plasma Catecholamines [ Time Frame: Blood draw will occur prior to ingestion of caffeine pill ]
  • 30 Minutes Following Ingestion of Caffeine Pill(s), Concentration of Plasma Catecholamines [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Standing baseline blood draw, prior to maximal exercise test ]
  • 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 ]
  • 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 ]
  • Heart Rate Collected During Cold Pressor Test [ Time Frame: Collected throughout the Cold Pressor Test, around 6 minutes in total ]
  • Standing Baseline Heart Rate, Prior to Fear Simulations [ Time Frame: Standing baseline, prior to fear simulations, up to or around 5 minutes ]
  • Heart Rate, First Fear Simulation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline seated heart rate recordings will occur prior to application of pain patch, up to or around 5 minutes ]
  • Heart Rate, During Pain Patch [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Seated heart rate recordings will occur following a 12-hour fast, up to or around 15 minutes. ]
  • Heart Rate, Seated Baseline, Caffeine Consumption [ Time Frame: Resting baseline heart rate will be recording prior to caffeine consumption, up to or around 5 minutes ]
  • Heart Rate, Following Caffeine Consumption [ Time Frame: Continuous heart rate recordings will occur immediately following caffeine consumption, up to or around 60 minutes. ]
  • Heart Rate, Baseline Prior to Maximal Exercise Test [ Time Frame: Baseline heart rate recordings will occur prior to the maximal exercise test, up to or around 5 minutes. ]
  • 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 ]
  • 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 ]
  • Blood Pressure Collected During Cold Pressor Test [ Time Frame: Collected throughout the Cold Pressor Test, around 6 minutes in total ]
  • Standing Baseline Blood Pressure, Prior to Fear Simulations [ Time Frame: Standing baseline, prior to fear simulations, up to or around 5 minutes ]
  • Blood Pressure, First Fear Simulation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline seated blood pressure recordings will occur prior to application of pain patch, up to or around 5 minutes ]
  • Blood Pressure, During Pain Patch [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Seated blood pressure recordings will occur following a 12-hour fast, up to or around 15 minutes. ]
  • Blood Pressure, Seated Baseline, Caffeine Consumption [ Time Frame: Resting baseline blood pressure will be recording prior to caffeine consumption, up to or around 5 minutes ]
  • Blood Pressure, Following Caffeine Consumption [ Time Frame: Continuous blood pressure recordings will occur immediately following caffeine consumption, up to or around 60 minutes. ]
  • Blood Pressure, Baseline Prior to Maximal Exercise Test [ Time Frame: Baseline blood pressure recordings will occur prior to the maximal exercise test, up to or around 5 minutes. ]
  • Blood Pressure, Maximal Exercise Test [ Time Frame: Continuous blood pressure recordings will take place throughout the maximal aerobic exercise test on the treadmill, up to or around 20 minutes ]

Central Contacts and Locations

Central contacts

Sara R Sherman, PhD

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

Constance Brecl

constance.brecl@cuanschutz.edu

Locations

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

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Joaquin M Espinosa, PhD

303-724-7389joaquin.espinosa@cuanschutz.edu

Angela Rachubinski, PhD

angela.rachubinski@cuanschutz.edu

More Information

Sponsor

University of Colorado, Denver

Last update posted

May 4, 2026

Last verified

Apr, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Colorado, Denver on 2026-05-04.