Clinical trial NCT03841669: Exercise, Brain, and Cardiovascular Health
Official title: Behavioral Studies of Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Keywords: Brain
Cardiovascular Disease
Exercise
Brain Health
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-02-15
Enrollment: 130
Sex: ALL
Minimum age (years): 26
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 130 individuals between the ages of 26 and 58 will be randomly assigned to one of two groups; Aerobic Exercise group or Physical Activity and Health Information group. The exercise group will receive moderate to vigorous intensity aerobic exercise targeting 150 minutes per week for 12 months. The group will target dividing these minutes into 3 exercise sessions a week over a 12-month period. Both groups will be asked to wear activity monitors every 6 weeks. Both groups will have fitness testing and cardiovascular assessments completed at baseline, 6 months (optional) and following the completion of the 12-month intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: eBACH is a randomized intervention to determine the effects of aerobic exercise on brain structure and function, as well as to determine how exercise-induced training effects relate to cardiovascular function via related brain changes.

Detailed description: Aim 1: To determine the neurobiology of exercise and cardiovascular factors: (1A) Body- to -Brain hypothesis: Exercise -induced changes in peripheral markers of cardiovascular health (e.g., cardiorespiratory fitness, peripheral vascular function) will precede and partly explain (statistically mediate) some of the exercise -induced changes in functional and structural features of areas defining visceral control circuits. (1B) Brain- to -Body hypothesis: Exercise -induced changes in functional and structural features of areas defining visceral control circuits precede and partly explain (statistically mediate) consequent changes in autonomic and neuroendocrine mediators of cardiovascular function that are under neural regulation, including baro-reflex sensitivity and heart rate variability. Aim 2: To determine the neurobiology of exercise self--reported correlates of cardiovascular function: (2A) Exercise will induce changes in visceral control areas engaged by functional magnetic resonance imaging (fMRI) tasks, and these changes will partly explain exercise- induced reductions in cardiovascular responsivity to challenges in daily life. (2B) Exercise will induce changes in visceral control areas engaged by an functional magnetic resonance imaging (fMRI) emotion processing and regulation paradigm, and these changes will partly explain exercise- induced improvements in affect measured in daily life by EMA and by conventional self- report instruments. The public health significance of this research is that it is designed to more precisely define and refine neurobiological targets to improve cardiovascular function and health.

Because of disruptions due to COVID-19, the study was placed into a compromised position that required conservation of funds and resources, resulting in a narrowing of focus and an abbreviated assessment protocol that limited the scale and scope of the longitudinal assessments and also reduced the sample size. As such, several of the secondary outcomes that were pre-specified were moved to "other pre-specified" during the course of the project.

Eligibility criteria: Inclusion Criteria:

* Age - individuals aged 26-58 years old
* Gender \& Ethnicity - men and women are both eligible to participate. The eBACH study expects the study population to be approximately 50% women. All ethnic groups are eligible for the study. The eBACH study expects the study population to be approximately 30% minorities.
* Ambulation - study participants must be able to walk without pain or use of an assisted walking device. This will be determined during the initial phone screen. Ambulation will also be assessed in person as the potential subject must be able to complete the VO2 Max test on a treadmill.
* Physical Activity Level - all participants must exercise less than 100 minutes per week and have a VO2max percentile level less than 75 based on the ACSM Guidelines for Exercise Testing (9th and 10th edition).
* Residency - Since the intervention is 12 months in duration, all potential participants must reside in the Pittsburgh area and plan on residing in the area for at least one year after randomization. It is recommended that the study coordinator during the second screen assess potential participants' distance from the exercising sites since the study requires 2 visits per week. The further a participant is from an intervention site, the higher the probability they will be unable to adhere to the protocol. In addition, participants must have reliable transportation to complete the outcome measures and the intervention requirements. Questions related to these considerations are asked during the phone screen and should also be assessed during the baseline visits.
* Willingness to be randomized - To be eligible, all potential study participants must be willing to be randomized to either of the intervention arms. Individuals that insist on participating only if they can choose which arm they belong to should not be enrolled.

Exclusion Criteria:

* Current use of prescribed blood pressure medication - participants who regularly use blood pressure medication will be excluded from the study.
* Self-reported chronic psychotic illness (schizophrenia, bipolar disorder) or neurological disorder (Parkinson's disease, dementia, MCI) - the eBACH study will exclude anyone who self-reports that they experience schizophrenia, bipolar disorder or parkinson's, dementia, or mild cognitive impairment.

  * Regular use of psychotropic medications - participants who regularly use psychotropic medications is defined as taking more than 7 times in a two week period will be excluded from the study (SSRIs are permitted)
* Current pregnancy or plans to become pregnant over the next year - any woman who is pregnant via the pregnancy test at the baseline visit will be excluded from the study. A pregnancy test will also be given at the MRI visit and this will be repeated at 6-months (if applicable) and 12-months.
* Self-reported prior heart attack, stroke, bypass surgery, angioplasty, congestive heart failure, arrhythmia (cardiac rhythm problems) - any person that reports that they have any of the health conditions listed above will be excluded from the study.
* Severe hypertension (sbp/dbp greater than/or equal to 160/100)

  * \>140/90 IS ALLOWED, but feedback card and information about elevated levels will be provided to the participant.
* Cancer - potential participants who have received treatment in the last 12 months for cancer, including radiation or chemotherapy will be excluded from the study. Although, if a potential participant who had non-melanoma skin cancer will be allowed to enroll in eBACH.
* Liver disease - any person who has had hepatitis B or C, liver failure or Cirrhosis will be excluded from the study.
* Kidney disease - potential participants who indicated they have chronic kidney failure, have undergone dialysis, or have had a kidney transplant will not be eligible to participant in the eBACH study.
* Type 1 diabetes and/or insulin treatment

  * Type 2 diabetics if they are taking insulin or 2 or more diabetes medications. Single injections that contain 2+ drugs count as 2 medications.
* Lung disease requiring drug treatment (any medication usage 3x/week in the last 2 weeks for chronic obstructive pulmonary disease (COPD), emphysema, asthma)

  * Rescue inhalers are okay.
* Non fluency in English - speaking/reading English everyday for \<10 years
* Nightshift work - the eBACH study for the purposes of the EMA monitoring will exclude any participants who work more than 12 night shifts in the last year, or participants who work more than one night shift per month on average. This is defined as a period of work in which half or more of the hours worked are between midnight and 8:00 in the morning.
* MRI incompatable

  * Certain medical devices, implants or other metal objects in or on the body that cannot be removed and are MRI incompatible
  * Inability to fit into the MRI scanner
  * Colorblindness
  * History of injury with metal object, metal in eye, welding or working in close proximity to welding without X-ray to prove lack of metal in the body.
* Suspected alcohol use disorder - for the eBACH study alcohol use disorder is defined as having five or more drinks at one time three times or more per week.
* Those who are otherwise unable to meet the requirements of the study (persons whose employment or personal situation will not permit momentary interruptions required for electronic diary and ambulatory data)

Primary outcomes:
measure: Change in Hippocampal Volume
timeFrame: Baseline & 12 months
Secondary outcomes:
measure: Change in Systolic Blood Pressure Responses to Behavioral Tasks
timeFrame: Baseline & 12 months
measure: Change in Heart Rate Variability (HRV)
timeFrame: Baseline & 12 months
Other outcomes:
measure: Change in fMRI
timeFrame: Baseline & 12 months
measure: Change in Reappraisal and Suppression Scores
timeFrame: Baseline, 6-month (if applicable) & 12 months
measure: Change in Perceived Stress Scale (PSS)
timeFrame: Baseline, 6-month (if applicable) & 12 months
measure: Change in Self-esteem
timeFrame: Baseline, 6-month (if applicable) & 12 months
measure: Change in Blood Pressure
timeFrame: Baseline, 6-month (if applicable), & 12 months
measure: Change in Cardiorespiratory Fitness
timeFrame: Baseline, 6-month (if applicable), & 12-month
measure: Change in Fasting Glucose.
timeFrame: Baseline, 6-month (if applicable) & 12 month
measure: Change in Insulin Resistance.
timeFrame: Baseline, 6-month (if applicable) & 12 month
measure: Mediation
timeFrame: Baseline, 6 month (if applicable) and 12 month.
measure: Change in Heart Rate
timeFrame: Baseline, 6-month (if applicable), & 12 months
measure: Change in Daily Life Ecological Monitoring Assessment (EMA)
timeFrame: Baseline & 12 months
measure: Change in Daily Life SBP Reactivity
timeFrame: Baseline & 12 months
measure: Change in Negative and Positive Affect
timeFrame: Baseline & 12 months
measure: Change in Baroreflex Sensitivity (BRS)
timeFrame: Baseline & 12 months
measure: Change in Pulse Wave Velocity (PWV)
timeFrame: Baseline & 12 months
measure: Change in Vasodilation (Reactive Hyperemia)
timeFrame: Baseline & 12 months
measure: Change in Brain Activity
timeFrame: Baseline & 12 months
measure: Change in Resting State Connectivity
timeFrame: Baseline & 12 months
measure: Change in Cortical Thickness.
timeFrame: Baseline & 12 months
measure: Change in Cortical Volume.
timeFrame: Baseline & 12 months
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Kirk I Erickson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Peter Gianaros, PhD
role: PRINCIPAL_INVESTIGATOR
References: