Clinical trial NCT02342808: Lifestyle Interventions in Treatment-Resistant Hypertension
Official title: Treating Resistant Hypertension Using Lifestyle Modification to Promote Health
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Treatment-Resistant Hypertension
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2015-01-21
Enrollment: 140
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the effects of lifestyle intervention on fitness, dietary habits, and body weight in patients with resistant hypertension (RH). Patients will be randomized to either a 4-month adjunctive lifestyle intervention designed to lower BP that will be delivered in a center-based CR program (C-LIFE), or to standardized education and physician advice (SEPA) designed to promote the same healthy behaviors and reflecting the current highest possible standard of care for promoting a healthy lifestyle in RH.

Detailed description: The term resistant hypertension (RH) is defined as clinic blood pressure (BP) that remains above goal (e.g., systolic blood pressure \[SBP\]\>140 mm Hg and/or diastolic blood pressure \[DBP\]\>90 mm Hg), despite adherence to a regimen of 3 or more antihypertensive medications of different classes, one of which is a diuretic.

With the growing prevalence of hypertension (HTN) in this country, RH is a major public health concern, affecting more than 7.5 million Americans. Patients with RH are 50% more likely to experience a CVD event, including stroke, kidney failure, myocardial infarction, and death, compared to patients with controlled BP. There is an urgent need for developing RH management strategies to lower BP as well as to reduce the high risk of CVD-related events. Lifestyle modifications, including exercise training and dietary modification, are of proven efficacy in lowering BP in unmedicated patients with HTN and are often recommended as the first step for treating high BP. The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to lower BP in HTN patients who are not treated with drugs. Moreover, when the DASH diet is combined with exercise and caloric restriction, even greater, and quite marked, BP reductions can be achieved. However, the efficacy of these lifestyle modifications in HTN patients who are refractory to medical therapy is unknown. This application aims to build upon evidence supporting the value of lifestyle modifications in unmedicated patients with HTN by proposing a randomized clinical trial (RCT) that will evaluate whether an intensive, medically-supervised lifestyle intervention can successfully lower BP in medicated patients with RH.

Eligibility criteria: 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

Primary outcomes:
measure: Change in clinic systolic blood pressure
timeFrame: Baseline to immediate post-treatment (4 months)
Secondary outcomes:
measure: Change in 24-hour ambulatory systolic blood pressure
timeFrame: Baseline to immediate post-treatment (4 months)
measure: Weight
timeFrame: Immediate post-treatment (4 months)
measure: Aerobic capacity (Measured via an exercise treadmill stress test with VO2 collection)
timeFrame: Immediate post-treatment (4 months)
measure: DASH Diet adherence (Measured via food diary recall)
timeFrame: Immediate post-treatment (4 months)
measure: Change in Cardiovascular Disease (CVD) biomarker composite score
timeFrame: Baseline to immediate post-treatment (4 months)
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: James A. Blumenthal, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Andrew Sherwood, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blumenthal JA, Hinderliter AL, Smith PJ, Mabe S, Watkins LL, Craighead L, Ingle K, Tyson C, Lin PH, Kraus WE, Liao L, Sherwood A. Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial. Circulation. 2021 Oct 12;144(15):1212-1226. doi: 10.1161/CIRCULATIONAHA.121.055329. Epub 2021 Sep 27.
citation: Smith PJ, Mabe SM, Sherwood A, Doraiswamy PM, Welsh-Bohmer KA, Burke JR, Kraus WE, Lin PH, Browndyke JN, Babyak MA, Hinderliter AL, Blumenthal JA. Metabolic and Neurocognitive Changes Following Lifestyle Modification: Examination of Biomarkers from the ENLIGHTEN Randomized Clinical Trial. J Alzheimers Dis. 2020;77(4):1793-1803. doi: 10.3233/JAD-200374.
citation: 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.