Effect of Exercise on Biomarkers in SCT

NCT04273022 | Completed DMC

• 1 other identifier: 30577
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Trait

Keywords

Sickle Cell Trait

Outcome Measures

Primary Outcomes (15)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

SCT Group

EXPERIMENTAL

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

Control Group

ACTIVE COMPARATOR

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

Interventions

Exercise OTHER

A single bout of standardized, moderate exercise

Control Group; SCT Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Louis University: lead
• American Society for Clinical Laboratory Science: collaborator

Study Sites (1)

Saint Louis University

St Louis, Missouri, 63104-1111, United States

Location

MeSH Terms

Conditions

Sickle Cell Trait

Interventions

Exercise

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Tim R Randolph, PhD

  St. Louis University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blood and urine samples will be assigned a random code. Testing personnel will be blinded to whether samples are pre- or post-exercise and whether from the SCT or control group.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: SCT subjects will be evaluated for activation of five physiological pathways by measuring 15 biomarkers before and after a single bout of moderate exercise. The control group will confirm normal biomarkers at rest and determine the natural response to moderate exercise.

Study Record Dates

• First Submitted: February 11, 2020
• First Posted: February 17, 2020
• Study Start: December 27, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available beginning 3 months after article publication for a period of 3 years after article publication
• Access Criteria: Proposals from outside investigators requesting permission to access data can be made to the PI at tim.randolph@health.slu.edu

Locations

US (1)