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Effect of Exercise on Biomarkers in SCT

Primary Purpose

Sickle Cell Trait

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise
Sponsored by
St. Louis University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Sickle Cell Trait focused on measuring Sickle Cell Trait

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Saint Louis UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

SCT Group

Control Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).

Secondary Outcome Measures

Full Information

First Posted
February 11, 2020
Last Updated
January 25, 2023
Sponsor
St. Louis University
Collaborators
American Society for Clinical Laboratory Science
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1. Study Identification

Unique Protocol Identification Number
NCT04273022
Brief Title
Effect of Exercise on Biomarkers in SCT
Official Title
The Effect of Exercise on Resting Biomarkers in Subjects With Sickle Cell Trait
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 27, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Louis University
Collaborators
American Society for Clinical Laboratory Science

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Trait
Keywords
Sickle Cell Trait

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
Outcomes Assessor
Masking Description
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.
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SCT Group
Arm Type
Experimental
Arm Description
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.
Arm Title
Control Group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Exercise
Intervention Description
A single bout of standardized, moderate exercise
Primary Outcome Measure Information:
Title
Change in reticulocyte count
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in erythrocyte morphology amounts
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in haptoglobin level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in potassium (K+) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in creatine kinase (CK) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in serum myoglobin level
Description
Myoglobin will be measured in urine, analyzed by electrochemiluminescent Immunoassay or nephelometry and reported in ng/mL (nanograms/milliliter). Elevated myoglobin suggests myocyte destruction.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in urine myoglobin level
Description
Myoglobin will be measured in urine, analyzed by electrochemiluminescent immunoassay or nephelometry and reported in mg/L (milligrams/liter). Elevated myoglobin suggests myocyte destruction.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in D-dimer level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in fibrin monomer level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in antithrombin III (ATIII) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in C-reactive protein (CRP) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in erythrocyte sedimentation rate (ESR) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in 11-dehydrothrombaxaneB2 (11-DTXB2) level
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in complete urinalysis results
Description
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.
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill
Title
Change in microalbumin level
Description
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).
Time Frame
Immediately before, immediately after, & 24 hours after a single bout of submaximal exercise on a treadmill

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tim R Randolph, PhD
Phone
3149778688
Email
tim.randolph@health.slu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kitty Newsham, PhD
Phone
31497778507
Email
katherine.newsham@health.slu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim R Randolph, PhD
Organizational Affiliation
St. Louis University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104-1111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tim R Randolph, PhD
Phone
314-977-8688
Email
tim.randolph@health.slu.edu
First Name & Middle Initial & Last Name & Degree
Katherine Newsham, PhD
Phone
3149778507
Email
katherine.newsham@health.slu.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

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Effect of Exercise on Biomarkers in SCT

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