Sympathetic Nervous System Function for Down Syndrome

(DIVE Trial)

Overseen By Sara R Sherman, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Colorado, Denver

Must be taking: Thyroid medications

Must not be taking: Heart-rate medications, Glucose-lowering

Disqualifiers: Hypertension, Hypotension, Cancer, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Are You a Good Fit for This Trial?

This trial is for individuals with Down syndrome who may have issues with their autonomic nervous system, affecting heart rate and blood pressure. Participants should be able to undergo various stress tests like fasting, exercise, and cold exposure without pre-existing conditions that could interfere.

Inclusion Criteria

Has a study partner who can attend all visits for the individuals with DS, and answer questionnaires, provide consent when necessary

BMI <45kg/m2

Ability to tolerate repeated blood draws / catheter placement

Exclusion Criteria

Hypotension (resting BP of <90/60 mmHg)

Tobacco products, including vaping, or marijuana use

Currently pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sympathetic Stressor Testing

Participants undergo testing for sympathetic nervous system responses to six stressors: Cold Stress, Fear, Pain, Caffeine, 12-Hour Fast, and Maximal Dynamic Exercise.

6 sessions

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after stressor testing

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exploring Sympathetic Nervous System Function

Trial Overview The study investigates how the sympathetic nervous system of those with Down syndrome responds to stress. It involves measuring heart rate, blood pressure, and hormone levels during different challenges such as fasting, caffeine intake, fear response tests, pain response evaluation, dynamic exercise, and cold exposure.

How Is the Trial Designed?

Group I: Individuals without Down syndrome Experimental Treatment 6 Interventions

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.

Group II: Individuals with Down syndrome Experimental Treatment 6 Interventions

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.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

GLOBAL Down Syndrome Foundation

Collaborator

Trials

1

Recruited

2,500+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Linda Crnic Institute for Down Syndrome

Collaborator

Trials

2

Recruited

103,000+

University of Colorado Colorado Clinical and Translational Sciences Institute

Collaborator