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Completed

NCT Number: NCT04273022

Effect of Exercise on Biomarkers in SCT

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.

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Key information

Conditions

Sickle Cell Trait Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Saint Louis University

St Louis, Missouri, 63104-1111, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Exercise

Other

A single bout of standardized, moderate exercise

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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).

Sponsors and collaborators

Lead sponsor

St. Louis University

Other

Collaborators

  • American Society for Clinical Laboratory Science

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Feb 17, 2020
Registry last updated
Jan 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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