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

Cold Stress

Maximal Dynamic Exercise

Isometric Handgrip Exercise with Post-Exercise Muscle Ischemia

Head-up Tilt Table Test

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

Sep, 2026

Completion date

Dec, 2030

Anticipated

Primary completion date

Dec, 2029

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

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 four 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 four sympathetic stressors.

Interventions

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.

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.

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.

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 measure

  • Seated Baseline Concentration of Plasma Catecholamines [ Time Frame: Seated baseline blood draw, prior to stressors ]
  • Standing Baseline Concentration of Plasma Catecholamines [ Time Frame: Blood draw will occur in standing position, prior to head up tilt table testing ]
  • Concentration of Plasma Catecholamines During Cold Pressor Test [ Time Frame: During the cold stress test, around or up to 5 minutes ]
  • Concentration of Plasma Catecholamines During Handgrip Test [ Time Frame: Blood draws occur around or up to 2-3 minutes into handgrip test ]
  • 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 ]
  • Supine Concentration of Plasma Catecholamines [ Time Frame: Blood draws during or around 10 minutes of supine rest ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Heart Rate Collected During Head-Up Tilt Table Test [ Time Frame: Collected throughout the Head-Up Tilt Table Test, around 25 minutes in total ]
  • 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 ]
  • Blood Pressure Collected During Head-Up Tilt Table Test [ Time Frame: Collected throughout the head-up tilt table test, around 25 minutes in total ]

Central Contacts and Locations

Central contacts

Sara R Sherman, PhD

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

Constance Brecl

DSResearch@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

303-724-7389DSResearch@cuanschutz.edu

Angela Rachubinski, PhD

DSResearch@cuanschutz.edu

More Information

Sponsor

University of Colorado, Denver

Last update posted

Oct 13, 2026

Last verified

Sep, 2026

Keywords

  • Cold Stress
  • Exercise
  • Blood Pressure
  • Heart Rate
  • Catecholamines
  • Epinephrine
  • Norepinephrine
  • Dopamine
  • Stress
  • Post-Exercise Muscle Ischemia
  • Handgrip
  • Head Up Tilt Table

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by University of Colorado, Denver on 2026-10-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.