Neurocognition, Lifestyle Modification, and Treatment Resistant Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Treatment-Resistant Hypertension
• Intervention / Treatment: Behavioral: Structured center-based lifestyle intervention; Behavioral: Standard education and physician advice

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Structured center-based lifestyle intervention; 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
Experimental: Standard education and physician advice; 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

What is the study measuring?

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	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)

Other 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 follow-up (1 year)
Processing Speed composite	Trail Making Test Part A, Stroop Word Section, Stroop Color Section, Digit Symbol, Ruff 2&7 Test	Baseline to follow-up (1 year)
Memory composite	CVLT-II Learning, CVLT-II Free Recall, RCFT Recall, Digit Spa	Baseline to follow-up (1 year)

Collaborators and Investigators

• Sponsor: Duke University

Publications and helpful links

General Publications

• Blumenthal JA, Sherwood A, Smith PJ, Mabe S, Watkins L, Lin PH, Craighead LW, Babyak M, Tyson C, Young K, Ashworth M, Kraus W, Liao L, Hinderliter A. Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial. Am Heart J. 2015 Nov;170(5):986-994.e5. doi: 10.1016/j.ahj.2015.08.006. Epub 2015 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): February 27, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: December 20, 2016
• First Posted (Estimate): December 23, 2016

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: Pro00055703_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No