Exercise-induced Erythropoiesis: the Mechanistic of Angiotensin II

Phase 4

Recruiting

• Conditions: Exercise Physiology
• Interventions: Drug: Valsartan 80 mg; Drug: Placebo

• Registration Number: NCT05269615
• Lead Sponsor: The University of Hong Kong

Brief Summary

The major aims are to determine the effect of acute (single dose) blockade of ANGII receptor 1 (AT1) on the EPO response to a single session of endurance exercise, as well as determine the effect of chronic (8-week) blockade of AT1 on ET-induced adaptations in total circulating red blood volume and hemoglobin.

Detailed Description

Physical activity, particularly when comprised of endurance training (ET) leading to cardiovascular adaptations, is considered the most effective intervention to augment life expectancy. Major health benefits induced by ET are closely associated (independently of traditional risk factors) with improvements in maximal oxygen consumption (VO2max), a hallmark of aerobic exercise capacity. The higher the VO2max the greater the likelihood to be free of cardiovascular disease, the main cause of mortality worldwide. Understanding the mechanisms explaining the improvement in VO2max with ET can provide sound basis for highly effective lifestyle and pharmacological interventions aimed to enhance cardiovascular health in the general population. So far, the essential role of ET-induced increased formation of red blood cells, i.e., erythropoiesis, has been firmly established for any improvement in VO2max. Yet, the underlying mechanism remains elusive. Clinical studies and recent investigations by the PI point towards the endocrine effects of key hormones that regulate blood volume (BV). Notably, the impact of ET-induced changes in angiotensin II (ANGII), a multifaceted hormone that modulates erythropoiesis through its effects on kidney erythropoietin (EPO) production, has to be experimentally elucidated in humans.

Study Timeline

• Study First Submitted: 2022-02-04
• Study First Submitted QC: 2022-02-25
• Study First Posted: 2022-03-08
• Study Start: 2023-03-20
• Status Verified: 2023-12
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-09
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Healthy status, absence of current medical symptoms or medication limiting incremental exercise testing
• No history of cardiac, pulmonary or kidney disease.

Exclusion Criteria

• Individuals fulfilling the above criteria but currently involved in regular exercise training (> 5 hr/week)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Valsartan tablets	Valsartan 80 mg	-
Placebo tablets	Placebo	-

Primary Outcome Measures

Name	Time	Method
maximal oxygen consumption in ml/kg/min	10 weeks	Maximal oxygen consumption (VO2max), a hallmark of aerobic capacity, will be determined with continuous measurements of oxgyen uptake using an online gas collection system (Quark CPET, Cosmed, Italy)
stroke volume in ml/m2	10 weeks	Stroke volume (SV) will be determined as left ventricular end-diastolic volume (LVEDV) minus left ventricular end-systolic volume (LVESV)
Blood volume (BV)-regulating hormone: Plasma ANGII in ng/dL	10 weeks	Plasma ANGII concentrations will be quantified by means of established competitive enzyme immunoassays

Trial Locations

Locations (1)

School of Public Health; 🇭🇰 Hong Kong, Hong Kong