How the sympathetic (fight-or-flight) system works in adults with Down syndrome

Dysautonomia InVestigation in Individuals With Down SyndromE: DIVE Study

Phase 3 Interventional University of Colorado, Denver · NCT07238465

This study will test how the sympathetic nervous system responds to stressors like exercise, cold, pain, fear, and caffeine in adults with Down syndrome to see if their heart rate and blood pressure responses are reduced or altered.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment200 (estimated)
Ages18 Years to 50 Years
SexAll
SponsorUniversity of Colorado, Denver Academic / other
Locations1 site (Aurora, Colorado)
Trial IDNCT07238465 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional study will provoke sympathetic activation in adults with Down syndrome using standardized stressors including exercise, cold exposure, pain stimuli, fear responses, and caffeine. Investigators will record beat-to-beat heart rate and blood pressure, collect blood samples for catecholamine measurements, and use catheter-based monitoring when needed. Eligible participants are adults 18–50 years old without recent cardiovascular, pulmonary, inflammatory, or metabolic disease and must tolerate repeated blood draws and procedures after a 12-hour fast. Data will be compared to expected physiological responses to characterize whether sympathetic responses are blunted or otherwise different in this population.

Who should consider this trial

Good fit: Ideal candidates are adults with Down syndrome aged 18–50 who are apparently healthy (no recent cardiovascular/pulmonary/inflammatory/metabolic disease), euthyroid or on a stable thyroid dose, have BMI below 45 kg/m2, can tolerate repeated blood draws and catheter placement, and can bring a study partner to all visits.

Not a fit: People taking heart-rate–altering medications, with uncontrolled hypertension or hypotension, recent cancer, active cardiovascular disease, or who cannot tolerate blood draws or travel to the site are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the study could identify specific autonomic deficits in people with Down syndrome that guide targeted interventions to improve exercise tolerance and reduce cardiovascular risk.

How similar studies have performed: Small prior studies have reported blunted maximal heart-rate responses to exercise in Down syndrome, but comprehensive testing of sympathetic responses across multiple stressors is largely novel.

Eligibility criteria

Show full inclusion / exclusion criteria
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 this trial is running

Aurora, Colorado

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Down SyndromeAutonomic DysfunctionCold StressPain ResponsesFearExerciseBlood PressureHeart Rate
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.