Effect of Exercise on Biomarkers in SCT

Sickle Cell Trait Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04273022
• Other study ID #: 30577
• Status: Recruiting
• Phase: N/A
• Start date: December 27, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: St. Louis University
• Contact: Tim R Randolph, PhD
• Phone: 3149778688
• Email: tim.randolph[@]health.slu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Sickle Cell Trait

Intervention

Other:
• Exercise
A single bout of standardized, moderate exercise

Locations

Country	Name	City	State
United States	Saint Louis University	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
St. Louis University	American Society for Clinical Laboratory Science

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in reticulocyte count	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
Primary	Change in erythrocyte morphology amounts	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
Primary	Change in haptoglobin level	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
Primary	Change in potassium (K+) level	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
Primary	Change in creatine kinase (CK) level	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
Primary	Change in serum myoglobin level	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
Primary	Change in urine myoglobin level	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
Primary	Change in D-dimer level	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
Primary	Change in fibrin monomer level	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
Primary	Change in antithrombin III (ATIII) level	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
Primary	Change in C-reactive protein (CRP) level	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
Primary	Change in erythrocyte sedimentation rate (ESR) level	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
Primary	Change in 11-dehydrothrombaxaneB2 (11-DTXB2) level	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
Primary	Change in complete urinalysis results	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
Primary	Change in microalbumin level	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