Neurocognition, Lifestyle Modification, and Treatment Resistant Hypertension

Study Overview
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Brief Summary
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This application proposes to extend an ongoing NHLBI clinical trial (NCT02342808) examining the efficacy of a lifestyle intervention combining the Dietary Approaches to Stop Hypertension (DASH) diet with caloric restriction and aerobic exercise to lower and control BP in individuals with RH. In the parent trial, participants with RH will be randomized to either: (1) a 4-month adjunctive lifestyle intervention designed to lower BP through exercise and diet (C-LIFE), or; (2) a standardized education and physician advice (SEPA) control condition. The current protocol will collect additional assessments of neurocognition (executive function, processing speed, and memory), endothelial function (brachial artery flow-mediated dilation), and cerebrovascular reserve (a measure of prefrontal cortex tissue oxygenation) in 120 participants at baseline, following completion of the 4-month intervention, and again after one year, in order to examine neurocognitive improvements and their potential mediators.

Official Title
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Neurocognition, Lifestyle Modification, and Treatment Resistant Hypertension

Conditions
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Treatment-Resistant Hypertension

Intervention / Treatment
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* Behavioral: Structured center-based lifestyle intervention
* Behavioral: Standard education and physician advice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented resistant hypertension (RH). In the absence of a specific RH diagnosis, individuals being treated for two or more weeks with 3 antihypertensive medications of different classes, including a diuretic if tolerated, with clinic SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg, will be eligible. Individuals being treated with 4 or more antihypertensive medications, including a diuretic if tolerated, with SBP ≥ 120 or DBP ≥ 80 mm Hg will also be eligible. Adherent to prescribed medications Overweight (BMI ≥ 25 kg/m2) Sedentary Willing to be randomized to one of the 2 treatment groups and able to fully participate in intervention Informed consent Exclusion Criteria: Secondary HTN, non-adherence to anti-HTN medications Severe CKD (eGFR <40 ml/min/1.73m2) Severe ischemic heart disease (CCS Class 3 or 4 angina or evidence of ischemia at <85% heart rate reserve on treadmill testing) Severe heart failure (NYHA association Class 3 or 4), high grade arrhythmias, severe valvular heart disease Severe asthma or chronic obstructive lung disease Diabetes requiring insulin Musculoskeletal or neurologic problems that would preclude participation in aerobic exercise training Major psychiatric disorder, a history of drug abuse, alcohol consumption >14 drinks/week Life-limiting comorbid medical condition such as cancer Prior gastric bypass surgery Currently pregnant Cognitively impaired

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Structured center-based lifestyle intervention<br>The Structured center-based Lifestyle Intervention (C-LIFE) will include individualized plans for the DASH diet, weight management, and aerobic exercise. | Behavioral: Structured center-based lifestyle intervention<br> <br> |
| Experimental: Standard education and physician advice<br>The Medical Management with Standardized Education and Physician Advice (SEPA) will consist of encouragement to achieve an ideal body weight and engage in exercise as part of routine counseling in primary care, but no special program will be delivered to enhance the participants' ability to comply with these recommendations. | Behavioral: Standard education and physician advice<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Executive Function composite | Trail Making Test Part B, Stroop Color-Word Section, Animal Naming, COWA, CVLT-II Discrimination Index | Baseline to immediate post-treatment (4 months) | 
| Processing Speed composite | Trail Making Test Part A, Stroop Word Section, Stroop Color Section, Digit Symbol, Ruff 2&7 Test | Baseline to immediate post-treatment (4 months) | 
| Memory composite | CVLT-II Learning, CVLT-II Free Recall, RCFT Recall, Digit Spa | Baseline to immediate post-treatment (4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brachial Artery Flow-Mediated Dilation |  | Baseline to immediate post-treatment (4 months) | 
| Prefrontal Cortex Tissue Oxygenation Index |  | Baseline to immediate post-treatment (4 months) |