다운 증후군 환자의 교감 신경계 기능 탐구 (DIVE)
다운 증후군 환자의 자율신경계 이상 조사: DIVE 연구
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
Evolution has equipped each species with instinctual defense mechanisms to cope with environmental stressors, ensuring survival. Many of these mechanisms are driven by activation of the sympathetic nervous system (SNS), which orchestrates the "fight or flight" response. Systemic SNS activation extends across all organ systems, triggering the release of catecholamines to elevate heart rate (HR) and increase blood pressure (BP) to meet the heightened metabolic demands of the stressor and ensure the delivery of oxygen-rich blood to active tissues. Exercise, a potent sympathoexcitatory stressor, poses a major challenge to the oxygen transport system, requiring coordinated organ system function to increase both HR and BP. Dysregulated SNS activation can impair oxygen delivery, leading to reduced work capacity, quality of life, and is an independent predictor of morbidity and premature mortality. Therefore, experimental approaches to understand SNS activation in populations with reduced work capacity and premature morbidity, mortality is of upmost importance for improving health outcomes and quality of life on a population level.
Down syndrome (DS) is the most common chromosomal abnormality in the human population, with widespread effects across numerous tissues and organ systems, including accelerated biological aging. Individuals with DS exhibit reduced work capacity, with maximal HRs ~30 beats below normal, and face higher rates of premature morbidity and mortality than the general population. Notably, individuals with DS demonstrate blunted catecholamine response to the sympathetic stressor of maximal exercise, suggesting diminished SNS activation. Recent literature from this PI suggests altered peripheral blood flow and BP regulation among individuals with DS during large muscle mass exercise which immolates walking, or running- critical for survival. These findings align with recent evidence of hypoxic signaling, elevated heme metabolism, and stress erythropoiesis across the lifespan in this population. Together, these data suggest that impaired oxygen delivery, potentially linked to SNS dysregulation, may be more widespread in DS than previously recognized.
However, the role of SNS activation in the context of daily stressors which elevate both HR and BP, remains unclear. Understanding the mechanisms underlying SNS dysfunction in DS is crucial, as it likely contributes to many clinical and developmental challenges, including the underlying reduced work capacity and suggested autonomic dysfunction observed in this population. Addressing this gap may enable targeted therapies to enhance survival, longevity, and quality of life for individuals with DS. The investigators aim to systematically evaluate SNS activation through four stressors which mimic common stressors faced to any individual over the course of a day or lifespan. Through evaluation of plasma catecholamines, the investigators hope to elucidate the mechanisms and impact of catecholamine responses in individuals with DS compared typical responses observed among individuals without DS.
Aim 1. Characterize the catecholamine response to physiological stressors among individuals with DS. The investigators will assess SNS responses in individuals with DS and age- and sex-matched controls. Beat-to-beat HR and BP, along with plasma catecholamine levels will be collected in response to the following sympathetic stressors: A) Cold Stress, B) Handgrip with Post-Exercise Muscle Ischemia, C) Head-up Tilt, and D) Maximal Dynamic Exercise (VO2peak). Metabolomics and proteomics will be performed on the plasma samples and these efforts will help define the manifestations of hormonal SNS dysfunction in individuals with DS.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 3단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Sara R Sherman, PhD
- 전화번호: 303-724-0598
- 이메일: sara.r.sherman@cuanschutz.edu
연구 연락처 백업
- 이름: Constance Brecl
- 이메일: DSResearch@cuanschutz.edu
연구 장소
-
-
Colorado
-
Aurora, Colorado, 미국, 80045
- 모병
- Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus
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연락하다:
- Joaquin M Espinosa, PhD
- 전화번호: 303-724-7389
- 이메일: DSResearch@cuanschutz.edu
-
연락하다:
- Angela Rachubinski, PhD
- 이메일: DSResearch@cuanschutz.edu
-
-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: 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. |
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.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
|
|
실험적: 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. |
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.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
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.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Seated Baseline Concentration of Plasma Catecholamines
기간: Seated baseline blood draw, prior to stressors
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Seated baseline blood draw, prior to stressors
|
|
Standing Baseline Concentration of Plasma Catecholamines
기간: Blood draw will occur in standing position, prior to head up tilt table testing
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Blood draw will occur in standing position, prior to head up tilt table testing
|
|
Concentration of Plasma Catecholamines During Cold Pressor Test
기간: During the cold stress test, around or up to 5 minutes
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
During the cold stress test, around or up to 5 minutes
|
|
Concentration of Plasma Catecholamines During Handgrip Test
기간: Blood draws occur around or up to 2-3 minutes into handgrip test
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Blood draws occur around or up to 2-3 minutes into handgrip test
|
|
Concentration of Plasma Catecholamines During Post Exercise Muscle Ischemia
기간: Seated blood draw to occur, around or about 2-3 minutes into post exercise muscle ischemia
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Seated blood draw to occur, around or about 2-3 minutes into post exercise muscle ischemia
|
|
Supine Concentration of Plasma Catecholamines
기간: Blood draws during or around 10 minutes of supine rest
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Blood draws during or around 10 minutes of supine rest
|
|
Supine Concentration of Plasma Catecholamines, 5 Minutes into Head-Up Tilt
기간: At or around 5 minutes into the head-up tilt table stimulus
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
At or around 5 minutes into the head-up tilt table stimulus
|
|
Supine Concentration of Plasma Catecholamines, 10 Minutes into Head-Up Tilt
기간: At or around 10 minutes into the head-up tilt table stimulus
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
At or around 10 minutes into the head-up tilt table stimulus
|
|
Baseline Standing Concentration of Plasma Catecholamines Prior to Maximal Exercise Test
기간: Standing baseline blood draw, prior to maximal exercise test
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
Standing baseline blood draw, prior to maximal exercise test
|
|
Standing Concentration of Plasma Catecholamines at End of Maximal Exercise Test
기간: This blood draw will occur at the very end or immediately following the maximal exercise test on the treadmill
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
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
기간: This blood draw will occur around 30 minutes following the maximal exercise test on the treadmill
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
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
기간: This blood draw will occur at the around 60 minutes following the maximal exercise test on the treadmill
|
Investigators will use metabolomic techniques to quantify plasma concentrations of epinephrine, norepinephrine, and dopamine in all participants before, during (in some stressors), and after the four stressor tests. These metabolites will provide insight into sympathetic nervous system activation in individuals with Down syndrome compared to those without Down syndrome. |
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
기간: Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
|
Investigators will collect beat-to-beat heart rate recordings in all participants before, during (in some stressors), and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
|
|
Heart Rate Collected During Cold Pressor Test
기간: Collected throughout the Cold Pressor Test, around 6 minutes in total
|
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Collected throughout the Cold Pressor Test, around 6 minutes in total
|
|
Heart Rate, Maximal Exercise Test
기간: Continuous heart rate recordings will take place throughout the maximal aerobic exercise test on the treadmill, up to or around 20 minutes
|
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
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
기간: Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
|
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Resting seated baseline, prior to cold pressor test, up to or around 5 minutes
|
|
Blood Pressure Collected During Cold Pressor Test
기간: Collected throughout the Cold Pressor Test, around 6 minutes in total
|
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Collected throughout the Cold Pressor Test, around 6 minutes in total
|
|
Heart Rate Collected During Handgrip with Post-Exercise Muscle Ischemia
기간: Collected throughout the Handgrip tests with Post-Exercise Muscle Ischemia, around 12 minutes in total
|
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Collected throughout the Handgrip tests with Post-Exercise Muscle Ischemia, around 12 minutes in total
|
|
Heart Rate Collected During Head-Up Tilt Table Test
기간: Collected throughout the Head-Up Tilt Table Test, around 25 minutes in total
|
Investigators will collect beat-to-beat heart rate recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Collected throughout the Head-Up Tilt Table Test, around 25 minutes in total
|
|
Blood Pressure Collected During Handgrip Test with Post-Exercise Muscle Ischemia
기간: Collected throughout the handgrip test with post-exercise muscle ischemia, up to or around 12 minutes
|
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
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
기간: Collected throughout the head-up tilt table test, around 25 minutes in total
|
Investigators will collect beat-to-beat blood pressure recordings in all participants before, during, and after the four stressor tests. These cardiovascular perturbations will provide insight into sympathetic nervous system modulation in individuals with Down syndrome compared to those without Down syndrome. |
Collected throughout the head-up tilt table test, around 25 minutes in total
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Facial Affective Scale Score, Baseline Assessment
기간: Baseline Assessment of Facial Affective Scale, this will occur prior to any stressors.
|
Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score. This will take up to or around approximately 5 minutes to complete. |
Baseline Assessment of Facial Affective Scale, this will occur prior to any stressors.
|
|
Facial Affective Scale Score, Cold Pressor Test, 1.5 Minutes
기간: Assessment occurs around or up to 90 seconds (1.5 minutes) into cold water immersion
|
Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score. |
Assessment occurs around or up to 90 seconds (1.5 minutes) into cold water immersion
|
|
Facial Affective Scale Score, Cold Pressor Test, Finale
기간: Assessment occurs immediately following or during the last minute of the Cold Pressor Test, up to or around 6 minutes following placement of arm into cold
|
Investigators will use the validated 'Facial Affective Scale', which uses a series of nine drawn faces showing various degrees of emotional distress to help participants assess their emotional state. The nine faces represent a range of negative to positive affect, and each face having a specific value between 0.04 (maximum positive affect) and 0.97 (maximum negative affect). The chosen face's corresponding value is the Facial Affective Score. |
Assessment occurs immediately following or during the last minute of the Cold Pressor Test, up to or around 6 minutes following placement of arm into cold
|
공동 작업자 및 조사자
협력자
협력자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- 25-0503
- T32AG000279 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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