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

NCT03109795 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 201701762
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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).

Conditions

Anxiety; Hypertension

Outcome Measures

Primary Outcomes (1)

• Aortic Stiffness

  Aortic stiffness as determined by the carotid-femoral pulse wave velocity technique

  4 weeks

Study Arms (2)

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

Drug: Clonidine Pill

Hydrochlorothiazide

ACTIVE COMPARATOR

Hydrochlorothiazide is a blood pressure-lowering control condition to compare to the effects of clonidine

Drug: Hydrochlorothiazide

Interventions

Clonidine Pill DRUG

sympathetic nerve activity blockade

Clonidine

Hydrochlorothiazide DRUG

Blood pressure-lowering control condition

Hydrochlorothiazide

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

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MeSH Terms

Conditions

Anxiety Disorders; Hypertension

Interventions

Clonidine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Mental Disorders; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Study was terminated before any participants were randomized because of lack of funding.

Results Point of Contact

• Title: Professor
• Organization: University of Iowa

gary-pierce@uiowa.edu

319-335-9487

Study Officials

• Seth W Holwerda, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, parallel, double-blind

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 12, 2017
• Study Start: April 10, 2017
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: July 29, 2024
• Results First Posted: July 29, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)