The Effect of Exercise on Resting Biomarkers in Subjects With Sickle Cell Trait
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Change in haptoglobin level
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Change in haptoglobin level
时间窗: 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.
Change in creatine kinase (CK) level
时间窗: 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.
Change in reticulocyte count
时间窗: 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.
Change in urine myoglobin level
时间窗: 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.
Change in D-dimer level
时间窗: 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.
Change in erythrocyte morphology amounts
时间窗: 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.
Change in potassium (K+) level
时间窗: 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.
Change in serum myoglobin level
时间窗: 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.
Change in C-reactive protein (CRP) level
时间窗: 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.
Change in 11-dehydrothrombaxaneB2 (11-DTXB2) level
时间窗: 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.
Change in complete urinalysis results
时间窗: 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.
Change in fibrin monomer level
时间窗: 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.
Change in microalbumin level
时间窗: 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).
Change in antithrombin III (ATIII) level
时间窗: 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.
Change in erythrocyte sedimentation rate (ESR) level
时间窗: 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.
次要结局
未报告次要终点
研究者
Tim Randolph, PhD, MT (ASCP)
Professor
St. Louis University