Sympathetic Nervous System Function for Down Syndrome

(DIVE Trial)

CB
SR
Overseen BySara R Sherman, PhD
Age: 18 - 65
Sex: Any
Trial Phase: Phase 3
Sponsor: University of Colorado, Denver
Must be taking: Thyroid medications
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the sympathetic nervous system (SNS), which regulates heart rate and blood pressure during stress, functions in individuals with Down syndrome. Researchers aim to understand why these individuals often experience lower heart rates during exercise. The study will measure heart rate, blood pressure, and stress-related blood chemicals. Ideal candidates are adults with Down syndrome who have stable thyroid levels and no recent heart disease. Understanding these SNS differences could lead to improved treatments for enhancing exercise ability and quality of life. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

If you are taking any heart-rate-altering medications or medications that affect metabolic responses, you will need to stop taking them to participate in this trial.

What prior data suggests that this protocol is safe for individuals with Down syndrome?

Research shows that people with Down syndrome often experience issues with their autonomic nervous system (ANS), which regulates heart rate and blood pressure. One study found that individuals with Down syndrome have lower levels of a specific enzyme in their blood, potentially affecting their sympathetic nervous system (SNS). The SNS helps the body manage stress by adjusting heart rate and blood pressure.

Limited information exists about the safety of specifically testing SNS function in people with Down syndrome. However, the study's late phase suggests that earlier research has demonstrated the procedures' safety. The study focuses on measuring heart rate and blood pressure responses, which are generally safe and non-invasive. Participation involves comparing responses to stressors in a controlled setting, minimizing risks.

Overall, while direct safety data from the sources is lacking, the study's later phase often indicates that these methods have been well-tolerated in earlier studies.12345

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover how the sympathetic nervous system operates differently in individuals with Down syndrome. Unlike current approaches that often focus on managing symptoms, this study digs deeper into physiological responses to stress. By understanding these unique responses, the trial could pave the way for more targeted therapies that address the root causes of health issues in people with Down syndrome. This approach could lead to breakthroughs in personalized treatment and improved quality of life.

What evidence suggests that exploring sympathetic nervous system function might be effective for Down syndrome?

This trial will compare sympathetic nervous system function between individuals with and without Down syndrome. Research has shown that people with Down syndrome (DS) often have a less active sympathetic nervous system (SNS), which helps control heart rate and blood pressure. Studies have found that individuals with DS have a lower heart rate response to exercise, about 30 beats per minute less than expected. This indicates that their SNS, which helps the body quickly adjust during stress, doesn't function as well. Additionally, an enzyme linked to SNS function, called plasma dopamine beta-hydroxylase, is significantly lower in people with DS. These findings suggest a clear pattern of SNS issues in DS, potentially leading to reduced exercise capacity and affecting overall quality of life.12346

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
See 5 more

Exclusion Criteria

Hypotension (resting BP of <90/60 mmHg)
Tobacco products, including vaping, or marijuana use
Currently pregnant
See 10 more

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?

2

Treatment groups

Experimental Treatment

Group I: Individuals without Down syndromeExperimental Treatment6 Interventions
Group II: Individuals with Down syndromeExperimental Treatment6 Interventions

Find a Clinic Near You

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

Citations

Exploring Sympathetic Nervous System Function in ...

Dysregulated SNS activation can impair oxygen delivery, leading to reduced work capacity, quality of life, and is an independent predictor of ...

Down syndrome and the autonomic nervous system, an ...

Down syndrome is also associated with autonomic nervous system dysfunction, a comorbidity that is overlooked in discussions of perioperative care.

Evaluation of the sympathetic nervous system in trisomy-21 ...

Plasma DBH activity was significantly (p < 0·005) diminished in the Down's patients when compared to their parents, to age-matched controls or adult controls.

Exploring Sympathetic Nervous System Function in ...

Individuals with DS often exhibit blunted HR responses to exercise-typically ~30 beats per minute below expected levels-suggesting reduced ...

Cardiac and Sympathetic Activation are Reduced in Children ...

Compared to TD children, those with DS had significantly reduced HR changes post-event during NREM (DS: 21.4% ± 1.8%, TD: 26.6% ± 1.6%, change from late to post ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35156260/

Down Syndrome and the autonomic nervous system, an ...

Down syndrome is also associated with autonomic nervous system dysfunction, a comorbidity that is overlooked in discussions of perioperative care.