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Anxiety-mediated Impairments in Large Elastic Artery Function and the Autonomic Nervous System (ATLAS)

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ClinicalTrials.gov Identifier: NCT03109795
Recruitment Status : Recruiting
First Posted : April 12, 2017
Last Update Posted : March 12, 2018
Sponsor:
Information provided by (Responsible Party):
Seth Holwerda, University of Iowa

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Anxiety Hypertension Drug: Clonidine Pill Drug: Hydrochlorothiazide Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, parallel, double-blind
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Anxiety-mediated Impairments in Large Elastic Artery Function and the Autonomic Nervous System
Actual Study Start Date : April 10, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: 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
Drug: Clonidine Pill
sympathetic nerve activity blockade

Active Comparator: Hydrochlorothiazide
Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine
Drug: Hydrochlorothiazide
Blood pressure-lowering control condition




Primary Outcome Measures :
  1. Aortic stiffness [ Time Frame: 4 weeks ]
    Aortic stiffness as determined by the carotid-femoral pulse wave velocity technique



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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for participants with moderate-to-high anxiety to undergo drug intervention:

  • 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).

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03109795


Contacts
Contact: Seth W Holwerda, PhD 319-353-5650 seth-holwerda@uiowa.edu
Contact: Allene Gremaud, MS (319) 353-3037 allene-gremaud@uiowa.edu

Locations
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Allene Gremaud, MS    319-353-3037    allene-gremaud@uiowa.edu   
Sponsors and Collaborators
Seth Holwerda
Investigators
Principal Investigator: Seth W Holwerda, PhD University of Iowa

Publications:

Responsible Party: Seth Holwerda, Postdoctoral Research Fellow, University of Iowa
ClinicalTrials.gov Identifier: NCT03109795     History of Changes
Other Study ID Numbers: 201701762
First Posted: April 12, 2017    Key Record Dates
Last Update Posted: March 12, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Anxiety Disorders
Mental Disorders
Hydrochlorothiazide
Clonidine
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents