Effect of Exercise on Biomarkers in SCT

January 24, 2025 updated by: Tim Randolph, PhD, MT (ASCP), St. Louis University

The Effect of Exercise on Resting Biomarkers in Subjects With Sickle Cell Trait

This study measures the effect of exercise on a variety of biomarkers in blood and urine selected to evaluate the physiological pathways of hemolysis, myolysis, thrombosis, inflammation, and renal function in subjects with sickle cell trait. These pathways have been shown to be associated with adverse events in athletes and warfighters with SCT upon protracted, repeated, strenuous exertion. Changes in biomarkers post-exercise compared to pre-exercise (and compared to healthy controls) suggest activation of the associated pathway(s) which may contribute to exercise-related events in athletes and warfighters and subclinical complications in non-athletes.

Study Overview

Status

Status

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

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

Subjects with sickle cell trait and healthy controls will be subjected to a single bout of moderate, controlled exercise on a treadmill. Blood and urine samples will be collected before exercise, immediately after exercise, and 24 hours after exercise. Fifteen biomarkers, three selected to evaluate each of the five physiologic pathways previously listed, will be tested at each of the three time points. Abnormal biomarkers before exercise suggest chronic pathway activation while exacerbated levels after exercise suggest further activation stimulated by exercise. Biomarker levels 24 hours post-exercise will be used to evaluate continued pathway activation or pathway recovery. By definition, 95% of health controls will show normal biomarker levels pre-exercise and biomarker patterns post-exercise will serve as the expected standard by which to compare the test subjects.

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 (Actual)

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.
12

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.
  • Not Applicable

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.

Study Contact Backup

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63104-1111
        • Saint Louis University

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

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria: Sickle Cell Trait Group (AS)

  • Health subjects with sickle cell trait (AS)
  • Ages 18-70 years

Inclusion Criteria: Control group (AA)

  • Healthy subjects without sickle cell trait (AA)
  • Ages 18-70 years

Exclusion Criteria: Sickle Cell Trait group (AS) AND healthy controls (AA).

Subjects will be excluded if they:

  • weigh less than 110 pounds,
  • are pregnant,
  • have hemoglobinopathies (other than sickle cell trait) as determined by Hb electrophoresis,
  • have other self-reported conditions known to cause blood coagulation activation, myocyte destruction, hemolysis, chronic inflammation, or renal disease
  • any condition that places subjects at risk during exercise.

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: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

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.
Experimental: SCT Group
Fifteen SCT subjects will be recruited, consented, screened, and enrolled if they meet inclusion and exclusion criteria. Each subject will undergo a single bout of standardized exercise on a treadmill. Subjects will self-select treadmill speed at 0% grade and begin. After 3 minutes the grade will be increased by 1% every 2 minutes until the target heart rate (70% of heart rate reserve) is reached. Speed and grade will be held constant for 15 minutes, marking the end of the session.
Other: Exercise
A single bout of standardized, moderate exercise
Active Comparator: Control Group
Five healthy subjects will be recruited, consented, screened, and enrolled if they meet inclusion and exclusion criteria. Each subject will undergo a single bout of standardized exercise on a treadmill. Subjects will self-select treadmill speed at 0% grade and begin. After 3 minutes the grade will be increased by 1% every 2 minutes until the target heart rate (70% of heart rate reserve) is reached. Speed and grade will be held constant for 15 minutes, marking the end of the session.
Other: Exercise
A single bout of standardized, moderate exercise

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
Change in reticulocyte count
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Reticulocytes will be counting using a manual microscopic method (New Methylene Blue) from blood collected in EDTA and reported as percentage of reticulocytes per 100 erythrocytes. Elevated reticulocytes suggest the bone marrow response to hemolysis.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in erythrocyte morphology amounts
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Blood collected in EDTA will be smeared on a microscope slide, stained with Wright stain, and analyzed for abnormal morphologic forms with a particular interest in sickle cells. Each abnormal erythrocyte morphologic form will be reported on a Likert scale from 1-4+ as follows: 1+ (few abnormal cells); 2+ (approximately 1/3 abnormal cells); 3+ (approximately 1/2 abnormal cells); 4+ (>1/2 abnormal cells). Increasing numbers of sickle cells in response to exercise may be associated with increased hemolysis, myocyte destruction, inflammation, initiation of coagulation, and renal dysfunction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in haptoglobin level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Haptoglobin will be measured on serum collected in a clot tube and reported as mg/dL (milligrams/deciliter) using a radial immunodiffusion method. Low haptoglobin levels suggest intravascular hemolysis.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in potassium (K+) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Potassium will be measured in serum collected in a clot tube, analyzed by ion selective electrode, and reported in mEq/L (milliequivalents/liter) or mmole/L (millimoles/liter). Elevated potassium levels suggest intravascular hemolysis.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in creatine kinase (CK) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Creatine kinase will be measured in serum from a clot tube, analyzed spectrophotometrically by enzyme kinetics and reported in U/L (units [of enzyme activity]/liter. Elevated creating kinase levels suggest myocyte destruction in the post-exercise environment.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in serum myoglobin level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Myoglobin will be measured in urine, analyzed by electrochemiluminescent Immunoassay or nephelometry and reported in ng/mL (nanograms/milliliter). Elevated myoglobin suggests myocyte destruction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in urine myoglobin level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Myoglobin will be measured in urine, analyzed by electrochemiluminescent immunoassay or nephelometry and reported in mg/L (milligrams/liter). Elevated myoglobin suggests myocyte destruction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in D-dimer level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
D-dimer will be measured in citrated plasma, analyzed by immunoturbidimetry and reported in ug/mL (micrograms/milliliter). Elevated D-dimer suggests the initiation of abnormal clotting or an inflammatory reaction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in fibrin monomer level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Fibrin monomer will be measured in citrated plasma, analyzed by the hemeagglutination method, and reported as negative (normal) or positive (abnormal). Elevated fibrin monomers suggest the initiation of coagulation.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in antithrombin III (ATIII) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Antithrombin III will be measured in serum from a clot tube, analyzed by radial immunodiffusion, and reported in mg/dL (milligrams/deciliter). Low antithrombin III levels suggest the initiation of coagulation.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in C-reactive protein (CRP) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
C-reactive protein will be measured in serum from a clot tube, analyzed by radial immunodiffusion, and reported in mg/dL (milligrams/deciliter). Elevated C-reactive protein suggest an inflammatory reaction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in erythrocyte sedimentation rate (ESR) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Erythrocyte sedimentation rate will be measured on whole blood collected in EDTA using the Wintrobe method and reported in mm/hr (millimeters/hour). An elevated erythrocyte sedimentation rate suggests an inflammatory reaction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in 11-dehydrothrombaxaneB2 (11-DTXB2) level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
11-dehydrothromboxane B2 will be measured in urine using an enzyme-linked immunosorbant assay (ELISA) and will be reported as pg/mL of creatinine (picogram/milliliter of creatinine). 11-dehydrothrombozane B2 is a direct measure of platelet activation and an indirect measure of an inflammatory reaction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in complete urinalysis results
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
A 10 parameter dipstick and a microscopic examination of urine will be performed on each urine sample collected. Each of the 10 dipstick parameters will be reported according to the package insert. We will pay particular attention to intact RBCs on the dipstick and sediment as an indicator of glomerular dysfunction, free hemoglobin as an indicator of hemolysis, elevated protein as an indicator of renal dysfunction or hemoglobinuria or myoglobinuria (hemolysis), and specific gravity interpreted in the context of blood and protein levels (and glucose) as an indicator of renal dysfunction.
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Change in microalbumin level
Time Frame: Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Microalbumin will be measured in urine with a dipstick using the sulfonephthalein dye method as an indicator of renal dysfunction and reported in mg/L (millighrams/liter).
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill

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.
St. Louis University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
American Society for Clinical Laboratory Science

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tim R Randolph, PhD, St. Louis University

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.
December 27, 2021

Primary Completion (Actual)

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.
December 31, 2024

Study Completion (Actual)

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.
December 31, 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 11, 2020

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 13, 2020

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.
February 17, 2020

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.
March 25, 2025

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.
January 24, 2025

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.
January 1, 2025

More Information

Terms related to this study

Keywords

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.
  • 30577

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A final de-identified database of study data will be generated and used for data sharing. Written data sharing requests from outside researchers will be reviewed by the PI and other members of the research team. Sharing will require a written agreement between the involved parties, which specifies the following: (1) what data will be shared, (2) who will have access to the shared data, (3) how the data will be shared and where the shared data will be stored (including details about security for data transfer and storage), (4) when the data will be shared, and (5) details about the data (i.e. data formats/transformations for sharing, meta-data to be included, etc.). The agreement will also require a commitment to using the data only for the specified research purposes and a commitment to destroying or returning the data after analyses are completed. Before sharing occurs, the written agreement will also be reviewed and approved by the the appropriate University units.

IPD Sharing Time Frame

Data will be available beginning 3 months after article publication for a period of 3 years after article publication

IPD Sharing Access Criteria

Proposals from outside investigators requesting permission to access data can be made to the PI at tim.randolph@health.slu.edu

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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