Exercise-induced Erythropoiesis: the Mechanistic of Angiotensin II

May 8, 2024 updated by: The University of Hong Kong
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: David Montero Barril, PhD
  • Phone Number: 66924724
  • Email: dvmb@hku.hk

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • School of Public Health
        • Contact:
          • David Montero, PhD
          • Phone Number: 28315250
          • Email: dvmb@hku.hk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo tablets
Drug: Placebo
The participants will be randomly allocated in a 1:1 ratio to valsartan or placebo. Valsartan and placebo tablets will be indistinguishable in taste and smell. The protocol will be developed in a double-blind manner in that both participants and investigators will be blinded toward the intervention condition.
Active Comparator: Valsartan tablets
Drug: Valsartan 80 mg
The well-established angiotensin II receptor blocker (ARB) valsartan will be used in the present study to selectively block AT1 receptors. Valsartan is a generic medication widely used in hypertensive patients since 1996 as well as safely applied in physiological studies comprising healthy individuals.1-3 A minimal valsartan dose of 80 mg known to acutely reduce circulating EPO levels in healthy individuals will be provided 4 hours before starting Study 1 to optimize AT1 blockade according to valsartan's half-life.1-3 The same dose of valsartan (80 mg) will be provided 4 hours before each ET session in Study 2. The participants will be randomly allocated in a 1:1 ratio to valsartan or placebo. Valsartan and placebo tablets will be indistinguishable in taste, smell, appearance and dosage. The protocol will be developed in a double-blind manner in that both participants and investigators will be blinded toward the intervention condition.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
stroke volume in ml/m2
Time Frame: 10 weeks
Stroke volume (SV) will be determined as left ventricular end-diastolic volume (LVEDV) minus left ventricular end-systolic volume (LVESV)
10 weeks
maximal oxygen consumption in ml/kg/min
Time Frame: 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)
10 weeks
Blood volume (BV)-regulating hormone: Plasma ANGII in ng/dL
Time Frame: 10 weeks
Plasma ANGII concentrations will be quantified by means of established competitive enzyme immunoassays
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Hong Kong

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 20, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 4, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 25, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19200831

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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