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The goal of this study is to evaluate the effectiveness of a short-term (4 weeks) pharmacological blockade of sympathetic nerve activity (clonidine) on anxiety symptoms, vascular function, inflammation, muscle sympathetic nerve activity, and oxidant stress in individuals with moderate-to-high anxiety. Individuals who are interested in the study will be identified by an online screening survey and will be contacted by the research team; advertisements, flyers and mass emails will direct individuals to the online screening survey. Those deemed eligible to participate will be randomized to either the clonidine intervention or hydrochlorothiazide as a blood-pressure lowering control condition. If eligible participants are currently being treated with blood pressure-lowering medications, they will be asked to go off these medications for 2 weeks prior to and during the course of the study. During the 2 week washout of blood pressure-lowering medications, participants will have safety visits (2 additional visits) that include measurements of blood pressure at 4 days and 7 days after the beginning of the washout period before the intervention. Assessments of anxiety symptoms via various surveys, vascular function (via non-invasive, well-established techniques), inflammation, muscle sympathetic nerve activity, and oxidant stress will be performed at baseline and at the post intervention session. Similar baseline measurements will be performed in control subjects with low or no anxiety for comparison, but these individuals will not undergo the intervention.
Participants with moderate-to-high anxiety will have a total of 6 visits to the laboratory, which includes the screening and consent (visit 1). Visit 2 (baseline measurements) and visit 6 (post-intervention measurements) will be more extensive (~4.5 hours) compared to the other visits (~30 min). Participants completing the washout will have an additional 2 visits (~30 min each) before "visit 2." Control subjects with low or no anxiety will only participate in visit 1 (screening and consent ) and visit 2 (baseline measurements).
Anxiety disorders are the most common mental health problems in the United States, occurring in about 18% of adults per year, and a lifetime prevalence of approximately 28% (25). Importantly, anxiety disorders are associated with increased risk for sudden cardiac death and non-fatal myocardial infarction (27, 46) independent of other mood disorders (13, 15). However, establishing a clear consensus on the mechanism(s) by which chronic anxiety confers cardiovascular disease (CVD) risk has proven difficult. Previous studies examining the potential role of vascular dysfunction in subjects with anxiety have been confounded by co-morbidities (e.g., hypertension, smoking, obesity) (31, 38) and added psychiatric disorders (63). Additionally, studies focusing on the relation between anxiety and robust predictors of CVD mortality, such as large elastic artery (e.g., aortic, carotid) stiffness, have been lacking.
Anxiety is experienced as negative feelings of threat, restlessness, tension and irritability, and somatic symptoms, such as palpitations, sweating, trembling, and dry mouth (57). Patients with clinically diagnosed anxiety disorder demonstrate more than 2-fold increase in future CVD events (23). Despite the strong association between anxiety and CVD risk, there is currently a gap in knowledge describing potential mechanisms by which anxiety leads to CVD. Evidence suggests that chronically high levels of anxiety may be associated with the progression of subclinical atherosclerosis such as carotid artery intima-media thickness (38) and elevated inflammation (5, 44). Symptoms of anxiety may also lead to impairment in resistance vessel dilator function (53). However, few studies have examined large elastic artery stiffness in subjects with high levels of anxiety. This is clinically important because large elastic artery stiffness (i.e., carotid and aortic) is a robust independent risk factor for CVD events such as stroke and myocardial infarction (6, 19, 59, 61). Interestingly, greater large elastic artery stiffness (aortic) is observed with higher resting muscle sympathetic nerve activity (MSNA) in healthy individuals even after adjusting for BP (9, 55). In this regard, numerous studies have shown that high MSNA independent of any increase in blood pressure can have deleterious vascular (7, 17, 32), metabolic (2, 20), cardiac (50, 52), and renal effects (1, 14, 54). Higher tonic MSNA is an independent determinant of aortic artery stiffness as assessed by the gold standard carotid-femoral pulse wave velocity (PWV) in healthy humans (55). Even acute increases in MSNA, such as during mental stress which is a potent stimulus for increases in MSNA (3), can lead to transiently greater large elastic artery stiffness (40). Furthermore, in healthy humans, acute mental stress induces transient endothelial dysfunction (16), an important modulator of arterial stiffness. Given findings from previous studies (22) showing that anxiety symptoms are associated with indices of elevated sympathetic nerve activity (e.g., elevated circulating norepinephrine), lead us to our overall hypothesis that anxiety-induced sympathetic overactivity leads to increased large elastic artery (carotid and aortic) stiffness in subjects with chronic anxiety.
The purpose of this study is to 1) determine the extent to which measures of vascular and autonomic function (large elastic artery stiffness, vascular inflammation and baroreflex function) is impaired in subjects with moderate-to-high anxiety, and 2) test the magnitude by which short-term (4 weeks) sympathetic nerve activity blockade (clonidine) improves large elastic artery stiffness, vascular inflammation and baroreflex function in subjects with moderate-to-high levels of anxiety.
In healthy subjects, chronic anxiety has been associated with increased risk of cardiac events (13, 15, 23). Interestingly, evidence suggests baroreflex function is reduced in subjects with anxiety (48, 60), thus adding additional cardiac risk burden to this population. Consistent with this, impairment in cardiac baroreflex sensivity (BRS) is a significant predictor of cardiac arrhythmias and myocardial infarction mortality (29, 56). Moreover, reduced cardiac BRS is a sensitive predictor of mortality after myocardial infarction (28, 30), particularly in subjects with anxiety (47). Reduced baroreflex activation can be attributed, in part, to reduced distensibility of baroreceptor regions within the elastic carotid and aortic arteries as a result of increased arterial stiffness (8). Given the associated risk of cardiac BRS impairment with anxiety, and the increase in large elastic artery stiffness in this population, there is a critical need to examine whether reductions in SNA and large elastic artery stiffness ameliorates cardiac BRS impairment in subjects with anxiety, thus providing experimental support for the novel idea that anxiety leads to increased CVD risk at least in part through elevated large artery stiffness.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clonidine | Experimental | To test the magnitude by which short-term (4 weeks) sympathetic nerve activity blockade (clonidine) improves large elastic artery stiffness, vascular inflammation and baroreflex function in subjects with moderate-to-high levels of anxiety |
|
| Hydrochlorothiazide | Active Comparator | Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clonidine Pill | Drug | sympathetic nerve activity blockade |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Aortic Stiffness | Aortic stiffness as determined by the carotid-femoral pulse wave velocity technique | 4 weeks |
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Inclusion Criteria for participants with moderate-to-high anxiety to undergo drug intervention:
Age is > or = 18 and < or = 79 years
No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), or peripheral arterial disease.
Non-smokers, defined as no history of smoking or no smoking for at least the past 3 months.
Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Blood chemistries indicative of normal renal (creatinine <2.0mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L) or on stable thyroid medication with no dose change for 3 months.
Exclusion Criteria:
Current use of antihypertensive medications for reasons other than hypertension (e.g., hydrochlorothiazide for leg edema or kidney stone prevention, beta-blockers for tremor)
Difficult to control hypertension (e.g., on 2 or 3 antihypertensive medications)
Low blood pressure (e.g., systolic BP < 110 mmHg)
Hypertensive and have not been stable on their current antihypertensive medication regimen for at least 6 months
Blood pressure not controlled either on or off antihypertensive medications (e.g., BP > 150/100)
Current diagnosis or history of cancer, liver disease, HIV/AIDS
History of brain tumor, aneurysm or injury
Clinical diagnosis of mental health disorders such as bipolar disorder or schizophrenia
History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without LV ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, atherosclerosis.
Current tobacco user or history of tobacco use within the past 3 months (cigarettes, cigars, chewing tobacco, Hookah).
History of lung emphysema, chronic bronchitis or chronic obstructive pulmonary disease (COPD).
Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Serious neurologic disorders including seizures.
History of renal failure, dialysis or kidney transplant.
Use of any investigational products or investigational medical devices within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Recent flu-like symptoms within the past 2 weeks.
Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
History of rheumatoid arthritis, Grave's disease, systemic lupus erythamatosis, and Wegener's granulomatosis.
Taking anticoagulation, anti-seizure, or antipsychotic agents.
Start of or dose change to an antidepressant or anti-anxiety medication within the past 3 months (if no change in medication or dose in past 3 month, then subject will be eligible).
Immunodeficiency or systemic autoimmune disease.
History of bleeding disorders or conditions of the microcirculation (i.e. von Willebrand disease, Raynaud's disease).
History of co-morbid condition that would limit life expectancy to <1 year.
Taking chronic non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin, naproxen, acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®) and not able or willing to go off of for 2 weeks prior to each study visit.
Taking cox-2 inhibitors (Celebrex®, Vioxx®, etc) or allopurinol (Zyloprim®, Lopurin®, Aloprim®).
Taking steroids or biologics: corticosteroids (prednisone); methotrexate, infliximib (Remicade®), etaneracept (Enbrel®); anakinra (Kineret®).
Those who are currently donating blood, platelets, or plasma at the time of screening.
Vulnerable populations (prisoners, etc.) will not be eligible to participate in this study.
On weight loss drugs (i.e. orilistat (Xenical®), sibutramine (Meridia®), phenylpropanol-amine (Acutrim®)), or similar over-the-counter medications within 3 months of screening.
Any surgery within 30 days of screening
Those who currently donate blood, platelets, or plasma
Any condition that, in the view of the PI or Co-I, places the subject at high risk or poor treatment and study compliance.
We will also enroll 36 participants ages 18-79 years (50% men, 50% women) with low or no anxiety as control subjects to participate in only baseline testing (not participate in the drug intervention).
Inclusion criteria:
Willing and able to provide written, signed consent after the nature of the study has been explained, and prior to any research-related procedures.
Age is > or = 18 and < or = 79 years
No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), or peripheral arterial disease.
Non-smokers, defined as no history of smoking or no smoking for at least the past 3 months.
Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Blood chemistries indicative of normal renal (creatinine <2.0mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L) or on stable thyroid medication with no dose change for 3 months.
Exclusion Criteria:
Current use of clonidine or beta-blockers
Current use of antihypertensive medications for reasons other than hypertension (e.g., hydrochlorothiazide for leg edema or kidney stone prevention, beta-blockers for tremor)
Difficult to control hypertension (e.g., on 2 or 3 antihypertensive medications)
Low blood pressure (e.g., systolic BP < 110 mmHg)
Hypertensive and have not been stable on their current antihypertensive medication regimen for at least 6 months
Blood pressure not controlled either on or off antihypertensive medications (e.g., BP > 150/100)
Current diagnosis or history of cancer, liver disease, HIV/AIDS
History of brain tumor, aneurysm or injury
Clinical diagnosis of mental health disorders such as bipolar disorder or schizophrenia
History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without LV ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, atherosclerosis.
Current tobacco user or history of tobacco use within the past 3 months (cigarettes, cigars, chewing tobacco, Hookah).
History of lung emphysema, chronic bronchitis or chronic obstructive pulmonary disease (COPD).
Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Serious neurologic disorders including seizures.
History of renal failure, dialysis or kidney transplant.
Use of any investigational products or investigational medical devices within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Recent flu-like symptoms within the past 2 weeks.
Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
History of rheumatoid arthritis, Grave's disease, systemic lupus erythamatosis, and Wegener's granulomatosis.
Taking anticoagulation, anti-seizure, or antipsychotic agents.
Start of or dose change to an antidepressant or anti-anxiety medication within the past 3 months (if no change in medication or dose in past 3 month, then subject will be eligible).
Immunodeficiency or systemic autoimmune disease.
History of bleeding disorders or conditions of the microcirculation (i.e. von Willebrand disease, Raynaud's disease).
History of co-morbid condition that would limit life expectancy to <1 year.
Taking chronic non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin, naproxen, acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®) and not able or willing to go off of for 2 weeks prior to each study visit.
Taking cox-2 inhibitors (Celebrex®, Vioxx®, etc) or allopurinol (Zyloprim®, Lopurin®, Aloprim®).
Taking steroids or biologics: corticosteroids (prednisone); methotrexate, infliximib (Remicade®), etaneracept (Enbrel®); anakinra (Kineret®).
Those who are currently donating blood, platelets, or plasma at the time of screening.
Vulnerable populations (prisoners, etc.) will not be eligible to participate in this study.
On weight loss drugs (i.e. orilistat (Xenical®), sibutramine (Meridia®), phenylpropanol-amine (Acutrim®)), or similar over-the-counter medications within 3 months of screening.
Any surgery within 30 days of screening
Those who currently donate blood, platelets, or plasma
Any condition that, in the view of the PI or Co-I, places the subject at high risk or poor treatment and study compliance.
We will also enroll 36 participants ages 18-79 years (50% men, 50% women) with low or no anxiety as control subjects to participate in only baseline testing (not participate in the drug intervention). These subjects will be either lean (body mass index < 25) or on the obesity spectrum (body mass index > 30).
Because obesity is linked with hypertension and type 2 diabetes, enrollment of subjects may include those with pre-hypertension or hypertension (systolic blood pressure >/= 120 - <180 mmHg- average of at least 3 measurements 2 min apart after 10 min seated resting position), and/or pre-diabetes (defined as fasting blood glucose between 100-126 mg/dl, fasting blood glucose of 140-199 mg/dl at 120 min of an oral glucose tolerance test, or HbA1C of 6-6.5%) or type 2 diabetes (defined as fasting blood glucose between >126 mg/dl, fasting blood glucose of >199 mg/dl at 120 min of an oral glucose tolerance test, or HbA1C > 6.5%). These subjects may be taking anti-hypertensive and/or diabetes (anti-hyperglycemic) medications. Subjects will be asked to refrain from medications the morning of the study visit, and to bring their medications with them to take immediately following their study visit.
Inclusion criteria:
Willing and able to provide written, signed consent after the nature of the study has been explained, and prior to any research-related procedures.
Age is > or = 18 and < or = 79 years
No history of cardiovascular disease (e.g., heart attack, stroke, heart failure, valvular heart disease, cardiomyopathy), or peripheral arterial disease.
Non-smokers, defined as no history of smoking or no smoking for at least the past 3 months.
Normal resting 12-lead ECG (no evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Blood chemistries indicative of normal renal (creatinine <2.0mg/dl), liver (<3 times upper limit for ALT, AST), and thyroid function (TSH between 0.4 - 5.0 mU/L) or on stable thyroid medication with no dose change for 3 months.
Exclusion Criteria:
Current diagnosis or history of cancer, liver disease, HIV/AIDS
History of brain tumor, aneurysm or injury
Clinical diagnosis of mental health disorders such as bipolar disorder or schizophrenia
History of cardiovascular disease such as heart angioplasty/stent or bypass surgery, myocardial infarction, stroke, heart failure with or without LV ejection fraction <40%, cardiomyopathy, valvular heart disease, cardiomyopathy, heart transplantation, atherosclerosis.
Current tobacco user or history of tobacco use within the past 3 months (cigarettes, cigars, chewing tobacco, Hookah).
History of lung emphysema, chronic bronchitis or chronic obstructive pulmonary disease (COPD).
Abnormal resting 12-lead ECG (e.g., evidence of myocardial infarction, left ventricular hypertrophy, left-bundle branch block, 2nd or 3rd degree AV block, atrial fibrillation/flutter, atherosclerosis).
Serious neurologic disorders including seizures.
History of renal failure, dialysis or kidney transplant.
Use of any investigational products or investigational medical devices within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Recent flu-like symptoms within the past 2 weeks.
Pregnant or breastfeeding at screening, or planning to become pregnant (self or partner) at any time during the study. A urinary pregnancy test will be done on all females. If test is positive, the subject will be excluded.
History of rheumatoid arthritis, Grave's disease, systemic lupus erythamatosis, and Wegener's granulomatosis.
Taking anticoagulation, anti-seizure, or antipsychotic agents.
Start of or dose change to an antidepressant or anti-anxiety medication within the past 3 months (if no change in medication or dose in past 3 month, then subject will be eligible).
Immunodeficiency or systemic autoimmune disease.
History of bleeding disorders or conditions of the microcirculation (i.e. von Willebrand disease, Raynaud's disease).
History of co-morbid condition that would limit life expectancy to <1 year.
Taking chronic non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin, naproxen, acetaminophen (Tylenol®), ibuprofen (Advil®, Motrin®) and not able or willing to go off of for 2 weeks prior to each study visit.
Taking cox-2 inhibitors (Celebrex®, Vioxx®, etc) or allopurinol (Zyloprim®, Lopurin®, Aloprim®).
Taking steroids or biologics: corticosteroids (prednisone); methotrexate, infliximib (Remicade®), etaneracept (Enbrel®); anakinra (Kineret®).
Those who are currently donating blood, platelets, or plasma at the time of screening.
Vulnerable populations (prisoners, etc.) will not be eligible to participate in this study.
On weight loss drugs (i.e. orilistat (Xenical®), sibutramine (Meridia®), phenylpropanol-amine (Acutrim®)), or similar over-the-counter medications within 3 months of screening.
Any surgery within 30 days of screening
Those who currently donate blood, platelets, or plasma
Any condition that, in the view of the PI or Co-I, places the subject at high risk or poor treatment and study compliance.
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| Name | Affiliation | Role |
|---|---|---|
| Seth W Holwerda, PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10906160 | Background | Amann K, Rump LC, Simonaviciene A, Oberhauser V, Wessels S, Orth SR, Gross ML, Koch A, Bielenberg GW, VAN Kats JP, Ehmke H, Mall G, Ritz E. Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria in subtotally nephrectomized rats. J Am Soc Nephrol. 2000 Aug;11(8):1469-1478. doi: 10.1681/ASN.V1181469. | |
| 2040704 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Clonidine | To test the magnitude by which short-term (4 weeks) sympathetic nerve activity blockade (clonidine) improves large elastic artery stiffness, vascular inflammation and baroreflex function in subjects with moderate-to-high levels of anxiety Clonidine Pill: sympathetic nerve activity blockade |
| FG001 | Hydrochlorothiazide | Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine Hydrochlorothiazide: Blood pressure-lowering control condition |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Study was terminated before any participants were randomized
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Clonidine | To test the magnitude by which short-term (4 weeks) sympathetic nerve activity blockade (clonidine) improves large elastic artery stiffness, vascular inflammation and baroreflex function in subjects with moderate-to-high levels of anxiety Clonidine Pill: sympathetic nerve activity blockade |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Aortic Stiffness | Aortic stiffness as determined by the carotid-femoral pulse wave velocity technique | Study was terminated before any participant was randomized to groups. | Posted | 4 weeks |
|
Study terminated before randomization
Study terminated before randomization
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Clonidine | To test the magnitude by which short-term (4 weeks) sympathetic nerve activity blockade (clonidine) improves large elastic artery stiffness, vascular inflammation and baroreflex function in subjects with moderate-to-high levels of anxiety Clonidine Pill: sympathetic nerve activity blockade |
Not provided
Not provided
Study was terminated before any participants were randomized because of lack of funding.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor | University of Iowa | 319-335-9487 | gary-pierce@uiowa.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 13, 2020 | Jun 29, 2024 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003000 | Clonidine |
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D048288 | Imidazolines |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
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Randomized, parallel, double-blind
Not provided
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| Hydrochlorothiazide |
| Drug |
Blood pressure-lowering control condition |
|
| Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991 Jun;87(6):2246-52. doi: 10.1172/JCI115260. |
| 3596778 | Background | Anderson EA, Wallin BG, Mark AL. Dissociation of sympathetic nerve activity in arm and leg muscle during mental stress. Hypertension. 1987 Jun;9(6 Pt 2):III114-9. doi: 10.1161/01.hyp.9.6_pt_2.iii114. |
| 22659156 | Background | Arch JJ, Wolitzky-Taylor KB, Eifert GH, Craske MG. Longitudinal treatment mediation of traditional cognitive behavioral therapy and acceptance and commitment therapy for anxiety disorders. Behav Res Ther. 2012 Aug;50(7-8):469-78. doi: 10.1016/j.brat.2012.04.007. Epub 2012 May 7. |
| 18603621 | Background | Bankier B, Barajas J, Martinez-Rumayor A, Januzzi JL. Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. Eur Heart J. 2008 Sep;29(18):2212-7. doi: 10.1093/eurheartj/ehn326. Epub 2008 Jul 4. |
| 24239664 | Background | Ben-Shlomo Y, Spears M, Boustred C, May M, Anderson SG, Benjamin EJ, Boutouyrie P, Cameron J, Chen CH, Cruickshank JK, Hwang SJ, Lakatta EG, Laurent S, Maldonado J, Mitchell GF, Najjar SS, Newman AB, Ohishi M, Pannier B, Pereira T, Vasan RS, Shokawa T, Sutton-Tyrell K, Verbeke F, Wang KL, Webb DJ, Willum Hansen T, Zoungas S, McEniery CM, Cockcroft JR, Wilkinson IB. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol. 2014 Feb 25;63(7):636-646. doi: 10.1016/j.jacc.2013.09.063. Epub 2013 Nov 13. |
| 6394491 | Background | Bevan RD. Trophic effects of peripheral adrenergic nerves on vascular structure. Hypertension. 1984 Nov-Dec;6(6 Pt 2):III19-26. doi: 10.1161/01.hyp.6.6_pt_2.iii19. |
| 22934037 | Background | Bruno RM, Ghiadoni L, Seravalle G, Dell'oro R, Taddei S, Grassi G. Sympathetic regulation of vascular function in health and disease. Front Physiol. 2012 Jul 24;3:284. doi: 10.3389/fphys.2012.00284. eCollection 2012. |
| 21242459 | Background | Casey DP, Curry TB, Joyner MJ, Charkoudian N, Hart EC. Relationship between muscle sympathetic nerve activity and aortic wave reflection characteristics in young men and women. Hypertension. 2011 Mar;57(3):421-7. doi: 10.1161/HYPERTENSIONAHA.110.164517. Epub 2011 Jan 17. |
| 7543454 | Background | Chapleau MW, Cunningham JT, Sullivan MJ, Wachtel RE, Abboud FM. Structural versus functional modulation of the arterial baroreflex. Hypertension. 1995 Aug;26(2):341-7. doi: 10.1161/01.hyp.26.2.341. |
| 22728646 | Background | Dindo L, Recober A, Marchman JN, Turvey C, O'Hara MW. One-day behavioral treatment for patients with comorbid depression and migraine: a pilot study. Behav Res Ther. 2012 Sep;50(9):537-43. doi: 10.1016/j.brat.2012.05.007. Epub 2012 May 27. |
| 23292718 | Background | Fairfax ST, Padilla J, Vianna LC, Davis MJ, Fadel PJ. Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans. Am J Physiol Heart Circ Physiol. 2013 Mar 1;304(5):H759-66. doi: 10.1152/ajpheart.00842.2012. Epub 2013 Jan 4. |
| 21262417 | Background | Fiedorowicz JG, He J, Merikangas KR. The association between mood and anxiety disorders with vascular diseases and risk factors in a nationally representative sample. J Psychosom Res. 2011 Feb;70(2):145-54. doi: 10.1016/j.jpsychores.2010.07.010. Epub 2010 Sep 18. |
| 19268634 | Background | Fisher JP, Young CN, Fadel PJ. Central sympathetic overactivity: maladies and mechanisms. Auton Neurosci. 2009 Jun 15;148(1-2):5-15. doi: 10.1016/j.autneu.2009.02.003. Epub 2009 Mar 6. |
| 18180430 | Background | Frasure-Smith N, Lesperance F. Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease. Arch Gen Psychiatry. 2008 Jan;65(1):62-71. doi: 10.1001/archgenpsychiatry.2007.4. |
| 11076819 | Background | Ghiadoni L, Donald AE, Cropley M, Mullen MJ, Oakley G, Taylor M, O'Connor G, Betteridge J, Klein N, Steptoe A, Deanfield JE. Mental stress induces transient endothelial dysfunction in humans. Circulation. 2000 Nov 14;102(20):2473-8. doi: 10.1161/01.cir.102.20.2473. |
| 7635545 | Background | Grassi G, Giannattasio C, Failla M, Pesenti A, Peretti G, Marinoni E, Fraschini N, Vailati S, Mancia G. Sympathetic modulation of radial artery compliance in congestive heart failure. Hypertension. 1995 Aug;26(2):348-54. doi: 10.1161/01.hyp.26.2.348. |
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| Hydrochlorothiazide |
Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine Hydrochlorothiazide: Blood pressure-lowering control condition |
| BG002 | Total | Total of all reporting groups |
|
| Age, Continuous |
| Sex: Female, Male |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. |
| Region of Enrollment | participants |
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Hydrochlorothiazide | Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine Hydrochlorothiazide: Blood pressure-lowering control condition | 0 | 0 | 0 | 0 | 0 | 0 |
Not provided
Not provided
| D006571 |
| Heterocyclic Compounds |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |