Blood Flow and Blood Pressure Investigation in Down Syndrome

NCT05528549 | Completed Phase 3

• 1 other identifier: 2022-0310
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Down syndrome (DS) is a chromosomal condition that occurs in approximately 1 in 800 births worldwide, and causes impairments in physical function, including a reduced work capacity (as measured by VO2peak or aerobic capacity). Work capacity is important for activities of daily living, in order to live longer, healthier lives. Reduced work capacity stems in large part from autonomic dysfunction, which has been described in individuals with DS. Individuals with DS experience reduced sympathetic and parasympathetic control, which results in alterations in resting heart rate, blood pressure, and attenuated responses to sympathoexcitatory stimuli. Autonomic dysfunction may impair the ability to regulate blood flow and blood pressure to working muscles during exercise, which may cause a mismatch between oxygen supply and demand, further compromising the already reduced work capacity observed in individuals with DS. Utilization of a large muscle mass exercise, such as lower-limb dynamic exercise (similar to walking), requires a large shift in blood flow to match metabolic demand and allows the opportunity to evaluate blood flow regulation. Conversely, examination of the large changes in pressure in response to isometric exercise (i.e., a sustained contraction), allows for examination of the exercise pressor reflex as evoked by the isometric contraction. Thus, by comprehensively evaluating blood flow and blood pressure regulation, our work will further elucidate the mechanisms that underlay the reduced work capacity in individuals with DS. Improvement of overall work capacity for a population with reduced work capacity will guide future studies and exercise interventions aimed at helping to improve independence and quality of life, ultimately allowing individuals with DS to live longer, healthier lives. Aim 1 (Dynamic Exercise): To examine the effects of an acute bout of dynamic leg kicking at both relative and absolute intensity workloads on femoral blood flow to both exercising and non-exercising muscle, in individuals with and without DS. Aim 2 (Isometric Exercise): To examine the exercise pressor response to lower limb isometric exercise in individuals with and without DS.

Conditions

Down Syndrome

Keywords

Exercise; Blood Flow; Blood Pressure

Outcome Measures

Primary Outcomes (2)

• Blood Flow

  The investigators will use a Doppler ultrasound machine to assess lower limb blood flow during repeated leg contractions.

  During study visit 1, lower limb blood flow will be measured as a change from baseline to blood flow during leg contraction. It will also be measured as a change from baseline to post leg contraction blood flow.

• Blood Pressure

  The investigators will continuously measure blood pressure during a static leg contraction.

  During study visit 2, blood pressure will be measured as a change from baseline blood pressure to leg contraction blood pressure. It will also be measured as a change in baseline blood pressure to post leg contraction blood flow.

Study Arms (2)

Dynamic Exercise

EXPERIMENTAL

The investigators will look at leg blood flow during a seated leg-kicking test that is similar to biking. Leg blood flow will be measured in both the active and inactive legs. These measurements will be taken to examine how blood is directed (or controlled) during exercise.

Other: Exercise

Static Exercise

EXPERIMENTAL

The investigators will look at blood pressure responses to a sustained leg kick. Blood pressure should increase during the sustained contraction for people without Down syndrome.

Other: Exercise

Interventions

Exercise OTHER

The investigators are looking at how blood flow and blood pressure are regulated in individuals with Down syndrome, who have a reduced ability to do work. This study will compare individuals with Down syndrome to a control group without Down syndrome.

Dynamic Exercise; Static Exercise

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• yrs old and apparently healthy individuals
• Mild to moderate intellectual disability for individuals with DS
• Corrected congenital heart disease for individuals with DS
• Euthyroid or on stable thyroid medication for at least 6 months
• Free from cardiovascular, pulmonary, inflammatory, or metabolic disease
• BMI \<40kg/m2

You may not qualify if:

• 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 blood pressure \[BP\] of \<90/60 mmHg)
• Cancer in the last 6 months
• Any heart-rate-altering medications or any other medication that may modify metabolic responses
• Anti-inflammatory medication for 7 days prior to testing
• Self-reported diabetes or use of glucose lowering medication
• Tobacco products, including vaping, or marijuana use
• Premenopausal women who use non-oral contraceptives
• Non-English speakers
• Currently pregnant
• Inability to perform leg extension exercises or any orthopedic limitations that would prohibit seated, stationary leg kicking

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• American College of Sports Medicine: collaborator

Study Sites (1)

Disability, Health & Social Policy Building; Integrative Physiology Lab

Chicago, Illinois, 60612, United States

Location

Related Publications (2)

• Sherman SR, Jackson RE, Hibner BA, Lima NS, Cloud RM, Fernhall B, Baynard T. Blunted exercise hyperemic response to lower limb exercise in individuals with Down syndrome. Am J Physiol Heart Circ Physiol. 2025 Aug 1;329(2):H374-H387. doi: 10.1152/ajpheart.00080.2025. Epub 2025 Jun 30.

  PMID: 40588365 DERIVED

• Sherman SR, Jackson R, Lima NS, Hibner BA, Fernhall BO, Baynard T. Blunted Exercise Pressor Response to Isometric Knee Extension and Post-Exercise Ischemia in Individuals with Down Syndrome. Med Sci Sports Exerc. 2025 Apr 1;57(4):876-883. doi: 10.1249/MSS.0000000000003619. Epub 2024 Dec 3.

  PMID: 39625363 DERIVED

MeSH Terms

Conditions

Down Syndrome; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Robert Motl, Ph.D.

  University of Illinois at Chicago

  STUDY CHAIR

• Tracy Baynard, Ph.D.

  University of Massachusetts at Boston

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Graduate Student

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: September 6, 2022
• Study Start: September 1, 2022
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)