Anti-hypertensive Therapy and Exercise Treatment to Improve Vascular Health in Patients with Hypertension. (Antitension)

Anti-hypertensive Therapy and Exercise Treatment to Improve Vascular Health in Patients with Hypertension. a Randomized Controlled Trial.

This is a prospective, monocentric, randomized controlled trial to investigate the effect of anti-hypertensive treatment and/or individualized exercise training intervention on blood pressure and vascular health. Furthermore the investigators want to decipher mechanisms, which contribute to vascular health by analyzing changes in metabolism and cell function in relation to vascular reaction.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Vascular Function; Metabolism Changes; Fitness Testing
• Intervention / Treatment: Behavioral: Individualized exercise therapy; Behavioral: Lifestyle recommendations

Detailed Description

Arterial hypertension is a global health burden that affects the structure and function of large and small blood vessels and induces disease-specific end-organ damage. Exercise therapy is highly recommended in the treatment of arterial hypertension to reduce blood pressure and ameliorate hypertension-induced vascular damage. Previous exercise intervention studies have shown that exercise treatment improves vascular dysfunction independently of changes in blood pressure. Several sensitive vascular biomarkers exist that could optimize risk stratification and therapeutic decisions based on the progression of individual vascular damage in patients with arterial hypertension. However, individualized vascular assessment during anti-hypertensive treatment is not yet part of routine clinical practice. In order to improve clinical decision making from a personalized medicine perspective, it is essential to better understand which vascular biomarkers have the best sensitivity in detecting therapy-induced vascular adaptations and whether anti-hypertensive therapy with or without additional exercise improves vascular health in patients with hypertension. The proposed study will evaluate the effects of guideline-directed anti-hypertensive therapy with or without individualized exercise training intervention in 60 patients with hypertension and no previous medical treatment for one year. Regular outpatient assessments of blood pressure and large and small blood vessels will be performed every two months. Anti-hypertensive therapy will be based on the current guidelines of the European Society of Hypertension. The investigators aim to achieve the target blood pressure after six months of treatment. A further six-month follow-up is planned to assess the long-term effects of anti-hypertensive therapy, with or without additional individualized exercise training intervention, on blood pressure and macro- and microvascular health. In addition, the investigators will investigate the effect of metabolic changes induced by anti-hypertensive treatment or individualized exercise training intervention on vascular health.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Johannes Stegbauer, Prof. Dr.; Phone Number: +49 211 81 080 74; Email: Studienzentrum-Nephrologie@med.uni-duesseldorf.de
• Study Contact Backup: Name: Lukas Streese, PhD

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitätsklinik Düsseldorf
    • Contact: Lukas Streese, PhD
    • Contact: Lukas Streese, PhD; Phone Number: +49 211 81 080 74; Email: Studienzentrum-Nephrologie@med.uni-duesseldorf.de
    • Contact: Johannes Stegbauer, MD
    • Contact: Claudia Schmidt, PhD
    • Contact: Marta Kantauskaite, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- systolic hypertension grade I-II (BP values >140 mmHg to <180 mmHg) without anti-hypertensive medication treatment

Exclusion Criteria:

• no written informed consent
• age <18 years
• isolated diastolic hypertension
• medical contraindications for the exercise treatment (for example orthopedic problems or an abnormal ECG during the cardio respiratory exercise test)
• chronic eye diseases on both eyes (for example macular degeneration or glaucoma) or high intraocular pressure (>20 mmHg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Individualized exercise training group; Beside a guideline based anti-hypertensive therapy, patients in the intervention group will receive an individualized exercise training program 3x/week. Exercise training will be a combination of aerobic and resistance training and is based on each patient's individual fitness level. Regular contact between exercise physiologists and patients, as well as group sessions, will help patients to maintain a regular exercise program.	Behavioral: Individualized exercise therapy; Patients in the intervention group will receive an individualized exercise training program 3x/week.; Behavioral: Lifestyle recommendations; The lifestyle recommendation group will receive general recommendations such as salt reduction, higher physical activity levels and stress reduction.
Other: Control group; Beside a guideline based anti-hypertensive therapy, patients in the lifestyle recommendation group will receive general recommendations such as salt reduction, higher physical activity levels and stress reduction.	Behavioral: Lifestyle recommendations; The lifestyle recommendation group will receive general recommendations such as salt reduction, higher physical activity levels and stress reduction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the retinal vessel diameters compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	The retinal vessel diameters will be analyzed based on the arteriolar-to-venular diameter ratio (AVR).	From enrollment to the end of treatment after six month.
Effect of an guideline based anti-hypertensive therapy on the retinal vessel diameters.	Changes of retinal vessel diameters will be analyzed based on the arteriolar-to-venular diameter ratio (AVR).	From enrollment to the end of treatment after six month.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the systolic and diastolic blood pressure compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes in unattended systolic and diastolic blood pressure in mm Hg.	From enrollment to the end of treatment after six month.
Effect of an guideline based anti-hypertensive therapy on the systolic and diastolic blood pressure.	Changes in unattended systolic and diastolic blood pressure in mm Hg.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the microvascular endothelial function compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes in microvascular endothelial function will be analyzed by retinal arteriolar and venular flicker light-induced dilation.	From enrollment to the end of treatment after six month.
Effect of an guideline based anti-hypertensive therapy on the microvascular endothelial function.	Changes in microvascular endothelial function will be analyzed by retinal arteriolar and venular flicker light-induced dilation.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the arterial stiffness compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes in arterial stiffness will be analyzed based on the central pulse wave velocity.	From enrollment to the end of treatment after six month.
Effect of an guideline based anti-hypertensive therapy on arterial stiffness.	Changes in arterial stiffness will be analyzed based on the central pulse wave velocity.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on physical fitness compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes of physical fitness will be analyzed based on cardiopulmonary exercise tests to evaluate peak oxygen uptake (VO2peak).	From enrollment to the end of treatment after six month.
Effect of an guideline based anti-hypertensive therapy on physical fitness.	Changes of physical fitness will be analyzed based on cardiopulmonary exercise tests to evaluate peak oxygen uptake (VO2peak).	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the NO metabolism of stored blood samples compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes of the NO metabolism will be analyzed based on nitrite, nitrate, ADMA and SDMA with nuclear magnetic resonance spectroscopy and established ELISA kits based on collected and stored blood samples.	From enrollment to the end of treatment after six month.
Effect of a guideline based anti-hypertensive therapy on the NO metabolism of stored blood samples.	Changes of the NO metabolism will be analyzed based on nitrite, nitrate, ADMA and SDMA with nuclear magnetic resonance spectroscopy and established ELISA kits based on collected and stored blood samples.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on the metabolic profile of stored blood samples compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes of the metabolic profile of stored blood samples will be analyzed by liquid chromatography and high-resolution tandem mass spectrometry.	From enrollment to the end of treatment after six month.
Effect of a guideline based anti-hypertensive therapy on the metabolic profile of stored blood samples.	Changes of the metabolic profile of stored blood samples will be analyzed by liquid chromatography and high-resolution tandem mass spectrometry.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on systemic inflammation markers compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes of systemic inflammation markers, such as cytokines, will be analyzed by ELISA and OLINK based on stored blood samples.	From enrollment to the end of treatment after six month.
Effect of a guideline based anti-hypertensive therapy on systemic inflammation markers of stored blood samples.	Changes of systemic inflammation markers, such as cytokines, will be analyzed by ELISA and OLINK based on stored blood samples.	From enrollment to the end of treatment after six month.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on fat and muscle mass compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes in fat and muscle mass will be investigated by bioimpedance analysis.	From enrollment to the end of treatment after six month.
Effect of a guideline based anti-hypertensive therapy on fat and muscle mass.	Changes in fat and muscle mass will be investigated by bioimpedance analysis.	From enrollment to the end of treatment after six month.
The additional effect of an anti-hypertensive treatment plus an individualizes exercise therapy on intra- and extracellular water volume compared to a guideline based anti-hypertensive treatment with general lifestyle recommendations.	Changes in intra- and extracellular water volume will be investigated by bioimpedance analysis.	From enrollment to the end of treatment after six month.
Effect of a guideline based anti-hypertensive therapy on intra- and extracellular water volume.	Changes in intra- and extracellular water volume will be investigated by bioimpedance analysis.	From enrollment to the end of treatment after six month.

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: exercise training; endothelial function; cardiorespiratory fitness; retinal microcirculation; lifestyle treatment
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: 2023-2603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request, selected study data will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No