Clinical trial NCT02915874: Does Treating Anxiety Symptoms With ACT Improve Vascular Inflammation and Function?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anxiety
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2016-09-27
Enrollment: 72
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the effectiveness of a brief, intensive 1-day psychotherapy group intervention (Acceptance and Commitment Therapy, ACT), compared to a 12 week time control group on anxiety symptoms, vascular function, inflammation, muscle sympathetic nerve activity (mSNA), and oxidant stress. Similar measures will be performed at baseline in individuals with low or no anxiety for comparison. 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 the ACT intervention or a control group. Assessments of anxiety symptoms (via various surveys) and vascular function (via non-invasive, well-established techniques) will be performed at baseline and 12 weeks post-ACT group intervention session. In addition, reassessment of anxiety symptoms via aforementioned surveys will take place 6 weeks post-ACT group session. After 12 weeks, anxiety and vascular assessments will be repeated to re-evaluate severity of anxiety symptoms, vascular function, inflammation, and oxidant stress.

Detailed description: The investigators hypothesize that reducing the burden of anxiety symptoms using Acceptance and Commitment Therapy (ACT) will improve vascular function, inflammation, mSNA, and oxidant stress.

The investigation also explore other secondary endpoints related to oxidant stress and inflammation in vascular endothelial cells. If anxiety increases inflammation, then we predict that ACT will reduce circulating pro-inflammatory cytokines, and produce a phenotype of endothelial cell proteins reflecting decreased inflammation compared to pre-treatment. And if anxiety increases oxidative stress, then ACT should produce a phenotype of endothelial cell proteins reflecting decreased oxidant stress and increased nitric oxide synthase activity.

Eligibility criteria: 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 = 25 and \< or = 65 years of age.
* Healthy, as determined by health history questionnaire, blood chemistries, and 12-lead ECG.
* 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.
* If currently receiving treatment with or taking any of the following supplements, must be willing and able to discontinue taking for 2 weeks prior to each study visit and/or throughout the treatment period: Vitamin C, E or other multivitamins containing vitamin C or E; omega-3 fatty acids; Phosphodiesterase (PDE) 5 inhibitors (i.e. Viagra®, Cialis®, Levitra®, or Revatio®); PDE 3 inhibitors (e.g., cilostazol (Pletal®), milrinone, or vesnarinone).
* 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).

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 erythematosis, 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).
* Intention to start or current psychotherapy for anxiety and/or depression while enrolled in study.
* 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, infliximab (Remicade®), etanercept (Enbrel®); anakinra (Kineret®).
* Vulnerable populations (prisoners, etc.) will not be eligible to participate in this study.
* Current alcohol abuse.
* On weight loss drugs (i.e. orlistat (Xenical®), sibutramine (Meridia®), phenylpropanol-amine (Acutrim®)), or similar over-the-counter medications within 3 months of screening.
* Any condition that, in the view of the PI or Co-I, places the subject at high risk or poor treatment and study compliance.

Primary outcomes:
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline, 6 weeks and 12 weeks
Secondary outcomes:
measure: State-Trait Anxiety Inventory (STAI) - State Anxiety
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Flow-mediated Dilation of the Brachial Artery
timeFrame: Baseline and 12 weeks
measure: Pulse Wave Velocity (PWV)
timeFrame: Baseline and 12 weeks
measure: Forearm Blood Flow
timeFrame: Baseline and 12 weeks
measure: Muscle Sympathetic Nerve Activity
timeFrame: Baseline, 6 weeks and 12 weeks
measure: State-Trait Anxiety Inventory (STAI) - Trait Anxiety
timeFrame: Baseline, 6 weeks and 12 weeks
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Jess G Fiedorowicz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dindo L, Fiedorowicz JG, Boykin DM, Wooldridge N, Myers J, Ajibewa T, Stroud A, Kuwaye D, Liu Z, Pierce GL. A randomized controlled trial for symptoms of anxiety and depression: Effects of a 1-day acceptance and commitment training workshop. Ann Clin Psychiatry. 2021 Nov;33(4):258-269. doi: 10.12788/acp.0046.
citation: Fiedorowicz JG, Dindo L, Ajibewa T, Persons J, Marchman J, Holwerda SW, Abosi OJ, DuBose LE, Wooldridge N, Myers J, Stroud AK, Dubishar K, Liu Z, Pierce GL. One-day acceptance and commitment therapy (ACT) workshop improves anxiety but not vascular function or inflammation in adults with moderate to high anxiety levels in a randomized controlled trial. Gen Hosp Psychiatry. 2021 Nov-Dec;73:64-70. doi: 10.1016/j.genhosppsych.2021.09.009. Epub 2021 Sep 28.