Anxiety
Conditions
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.
Interventions
BEHAVIORALAcceptance and Commitment Therapy
Sponsors
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beck Anxiety Inventory (BAI) | Baseline, 6 weeks and 12 weeks | Self-report measure of anxiety. The test consists of 21 questions graded on a scale of 0 (not at all) to 3 (severely). Range of total score is 0 to 63. Higher scores indicate more severe anxiety symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated Dilation of the Brachial Artery | Baseline and 12 weeks | Flow-mediated dilation of the brachial artery will be assessed by ultrasound following a 5 minute distal occlusion. Larger values are better. Data was collected for the first 5 cohorts. |
| Pulse Wave Velocity (PWV) | Baseline and 12 weeks | Carotid-Femoral PWV (cm/sec) |
| State-Trait Anxiety Inventory (STAI) - State Anxiety | Baseline, 6 weeks and 12 weeks | Self-reported anxiety measures. STAI-Form Y-1 total score. Consists of 20 questions based on a 4-point Likert scale. Range of total score is 20 to 80. Higher scores indicate greater anxiety. |
| Muscle Sympathetic Nerve Activity | Baseline, 6 weeks and 12 weeks | Muscle sympathetic nerve activity will be measured directly through the peroneal nerve over a 30 minute recording. The processed signal for neural activity will be processed as bursts/minute. Data was collected for the last 3 cohorts. |
| State-Trait Anxiety Inventory (STAI) - Trait Anxiety | Baseline, 6 weeks and 12 weeks | Self-reported anxiety measure. STAI-Form Y2 total score. Consists of 20 questions based on a 4-point Likert scale. Range of total score is 20 to 80. Higher scores indicate greater anxiety. |
| Forearm Blood Flow | Baseline and 12 weeks | Forearm volume (FAV). Peak Forearm blood flow was assessed by plethysmography (mL/100 mL FAV/min). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention Subjects randomized to the ACT Intervention group will attend a 1-day group workshop in which two broad areas will be covered:
1. Behavioral Change training will involve a) teaching subjects how to recognize ineffective patterns of behavior and habits, b) exploring and setting life goals and those related to mental and physical health, and c) promoting effective and committed actions to achieve these goals despite the urge to do otherwise;
2. Mindfulness and Acceptance Training will emphasize new ways of managing troubling thoughts, feelings, and physical sensations (i.e. learning how to recognize, and develop cognitive distances from unhelpful thoughts such as I can't take this anymore and learning how to willingly face experiences that cannot be changed). In-session exercises and practice will be heavily emphasized during the group intervention and handouts will be distributed for home use.
Acceptance and Commitment Therapy | 44 |
| Control Subjects randomized to not receive treatment. | 28 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Started New Anxiety Medication | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Acceptance and Commitment Therapy Behavioral Intervention | Control | Total |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 8.7 | 37.1 years STANDARD_DEVIATION 10.1 | 34.6 years STANDARD_DEVIATION 9.4 |
| Body Mass Index | 26.1 kg/m^2 STANDARD_DEVIATION 4.8 | 29.6 kg/m^2 STANDARD_DEVIATION 6.3 | 27.4 kg/m^2 STANDARD_DEVIATION 5.6 |
| Education Level College Degree | 22 Participants | 14 Participants | 36 Participants |
| Education Level Graduate or Professional Degree | 20 Participants | 8 Participants | 28 Participants |
| Education Level Some College | 2 Participants | 6 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 26 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 36 Participants | 25 Participants | 61 Participants |
| Sex: Female, Male Female | 29 Participants | 20 Participants | 49 Participants |
| Sex: Female, Male Male | 15 Participants | 8 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 28 |
| other Total, other adverse events | 0 / 44 | 0 / 28 |
| serious Total, serious adverse events | 0 / 44 | 0 / 28 |
Outcome results
Primary
Beck Anxiety Inventory (BAI)
Self-report measure of anxiety. The test consists of 21 questions graded on a scale of 0 (not at all) to 3 (severely). Range of total score is 0 to 63. Higher scores indicate more severe anxiety symptoms.
Time frame: Baseline, 6 weeks and 12 weeks
Population: Subjects dropped out of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | Beck Anxiety Inventory (BAI) | Baseline | 18.750 score on a scale | Standard Deviation 8.334 |
| Acceptance and Commitment Therapy Behavioral Intervention | Beck Anxiety Inventory (BAI) | 6 weeks | 13.317 score on a scale | Standard Deviation 8.413 |
| Acceptance and Commitment Therapy Behavioral Intervention | Beck Anxiety Inventory (BAI) | 12 weeks | 11.053 score on a scale | Standard Deviation 8.077 |
| Control | Beck Anxiety Inventory (BAI) | Baseline | 17.464 score on a scale | Standard Deviation 7.951 |
| Control | Beck Anxiety Inventory (BAI) | 6 weeks | 16.154 score on a scale | Standard Deviation 8.624 |
| Control | Beck Anxiety Inventory (BAI) | 12 weeks | 14.727 score on a scale | Standard Deviation 10.315 |
p-value: 0.02Mixed Models Analysis
Secondary
Flow-mediated Dilation of the Brachial Artery
Flow-mediated dilation of the brachial artery will be assessed by ultrasound following a 5 minute distal occlusion. Larger values are better. Data was collected for the first 5 cohorts.
Time frame: Baseline and 12 weeks
Population: Data was collected for the first 5 cohorts.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | Flow-mediated Dilation of the Brachial Artery | Baseline | 3.448 percentage of flow-mediation dilation | Standard Deviation 4.884 |
| Acceptance and Commitment Therapy Behavioral Intervention | Flow-mediated Dilation of the Brachial Artery | 12 weeks | 4.269 percentage of flow-mediation dilation | Standard Deviation 3.243 |
| Control | Flow-mediated Dilation of the Brachial Artery | Baseline | 5.913 percentage of flow-mediation dilation | Standard Deviation 4.151 |
| Control | Flow-mediated Dilation of the Brachial Artery | 12 weeks | 4.574 percentage of flow-mediation dilation | Standard Deviation 2.231 |
p-value: 0.27Mixed Models Analysis
Secondary
Forearm Blood Flow
Forearm volume (FAV). Peak Forearm blood flow was assessed by plethysmography (mL/100 mL FAV/min).
Time frame: Baseline and 12 weeks
Population: Subjects dropped out of study and some measurements are missing at random.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | Forearm Blood Flow | Baseline | 23.546 mL/100 mL FAV/min | Standard Deviation 8.434 |
| Acceptance and Commitment Therapy Behavioral Intervention | Forearm Blood Flow | 12 weeks | 25.181 mL/100 mL FAV/min | Standard Deviation 8.431 |
| Control | Forearm Blood Flow | Baseline | 19.307 mL/100 mL FAV/min | Standard Deviation 4.943 |
| Control | Forearm Blood Flow | 12 weeks | 19.969 mL/100 mL FAV/min | Standard Deviation 7.444 |
p-value: 0.69Mixed Models Analysis
Secondary
Muscle Sympathetic Nerve Activity
Muscle sympathetic nerve activity will be measured directly through the peroneal nerve over a 30 minute recording. The processed signal for neural activity will be processed as bursts/minute. Data was collected for the last 3 cohorts.
Time frame: Baseline, 6 weeks and 12 weeks
Population: Last 3 cohorts were measured. Furthermore measurements are missing at random.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | Muscle Sympathetic Nerve Activity | Baseline | 13.890 bursts/minute | Standard Deviation 10.427 |
| Acceptance and Commitment Therapy Behavioral Intervention | Muscle Sympathetic Nerve Activity | 6 weeks | 13.343 bursts/minute | Standard Deviation 8.652 |
| Acceptance and Commitment Therapy Behavioral Intervention | Muscle Sympathetic Nerve Activity | 12 weeks | 19.104 bursts/minute | Standard Deviation 11.283 |
| Control | Muscle Sympathetic Nerve Activity | Baseline | 21.550 bursts/minute | Standard Deviation 11.476 |
| Control | Muscle Sympathetic Nerve Activity | 6 weeks | 23.967 bursts/minute | Standard Deviation 13.876 |
| Control | Muscle Sympathetic Nerve Activity | 12 weeks | 29.877 bursts/minute | Standard Deviation 11.835 |
p-value: 0.58Mixed Models Analysis
Secondary
Pulse Wave Velocity (PWV)
Carotid-Femoral PWV (cm/sec)
Time frame: Baseline and 12 weeks
Population: Subjects dropped out. There are additional measurements which are missing at random.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | Pulse Wave Velocity (PWV) | 12 weeks | 620.608 cm/sec | Standard Deviation 183.534 |
| Acceptance and Commitment Therapy Behavioral Intervention | Pulse Wave Velocity (PWV) | Baseline | 630.335 cm/sec | Standard Deviation 254.534 |
| Control | Pulse Wave Velocity (PWV) | Baseline | 640.811 cm/sec | Standard Deviation 144.177 |
| Control | Pulse Wave Velocity (PWV) | 12 weeks | 639.938 cm/sec | Standard Deviation 158.349 |
p-value: 0.98Mixed Models Analysis
Secondary
State-Trait Anxiety Inventory (STAI) - State Anxiety
Self-reported anxiety measures. STAI-Form Y-1 total score. Consists of 20 questions based on a 4-point Likert scale. Range of total score is 20 to 80. Higher scores indicate greater anxiety.
Time frame: Baseline, 6 weeks and 12 weeks
Population: Subjects dropped out.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - State Anxiety | Baseline | 43.227 score on a scale | Standard Deviation 9.246 |
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - State Anxiety | 6 weeks | 43.000 score on a scale | Standard Deviation 12.538 |
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - State Anxiety | 12 weeks | 39.658 score on a scale | Standard Deviation 11.516 |
| Control | State-Trait Anxiety Inventory (STAI) - State Anxiety | Baseline | 44.143 score on a scale | Standard Deviation 6.98 |
| Control | State-Trait Anxiety Inventory (STAI) - State Anxiety | 6 weeks | 48.885 score on a scale | Standard Deviation 9.688 |
| Control | State-Trait Anxiety Inventory (STAI) - State Anxiety | 12 weeks | 42.682 score on a scale | Standard Deviation 10.895 |
p-value: 0.19Mixed Models Analysis
Secondary
State-Trait Anxiety Inventory (STAI) - Trait Anxiety
Self-reported anxiety measure. STAI-Form Y2 total score. Consists of 20 questions based on a 4-point Likert scale. Range of total score is 20 to 80. Higher scores indicate greater anxiety.
Time frame: Baseline, 6 weeks and 12 weeks
Population: Subjects dropped out of study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | Baseline | 53.205 score on a scale | Standard Deviation 7.893 |
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | 6 weeks | 46.902 score on a scale | Standard Deviation 11.975 |
| Acceptance and Commitment Therapy Behavioral Intervention | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | 12 weeks | 44.842 score on a scale | Standard Deviation 11.305 |
| Control | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | Baseline | 56.179 score on a scale | Standard Deviation 8.748 |
| Control | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | 6 weeks | 53.846 score on a scale | Standard Deviation 9.456 |
| Control | State-Trait Anxiety Inventory (STAI) - Trait Anxiety | 12 weeks | 51.136 score on a scale | Standard Deviation 9.662 |
p-value: 0.08Mixed Models Analysis