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NCT Number: NCT02571088

Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients

Sickle cell disease (SCD) is the most frequent inherited disease in the world. Literature reports that SCD patients display intolerance to exercise, important muscle weakness and profound remodeling of skeletal muscle including amyotrophy and rarefied microvascular network.

Because strenuous exercise induces acidosis, hemorheological alterations, endothelial activation and oxidative stress, it constitutes a potential triggering factor of sickling and vaso-occlusive crisis. As a consequence, physical activity is usually discouraged in patients with SCD. However, moderate and regular physical activity seems to be not only safe but also beneficial for SCD patients.

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Key information

Conditions

Sickle Cell Hemoglobin C Disease 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 Hemoglobin S Disease Hemoglobin SC Disease Hemoglobinopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hopital Avicenne, Bobigny, France

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About this study

Besides, endurance training is known to induce moderate muscle hypertrophy and increase microvascular network. Therefore, adapted, moderate and regular physical activity appears as a potential strategy able to improve muscle function, decrease symptoms of the disease and improve autonomy and quality of life of patients with SCD. However, it remains necessary to define the modalities of exercise therapy in SCD and to objectively evaluate the risks, limitations and gains on physical ability, muscle function and quality of life in patients with SCD.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Sickle cell disease patient (HbSS or HbS-βthal0),
  • Affiliated to a Health Security program,
  • Consent form signed,
  • Patients in stabilized state at the onset of the experiment: at least one month after an acute adverse event and at least 3 months after a blood transfusion.

Exclusion criteria

  • Patients whom adhesion/compliance to the protocol appears uncertain,
  • Patient involved in another clinical trial or within the exclusion period of a previous clinical trial,
  • Patients known to be affected by a chronic inflammatory or infectious pathology,
  • Patients having an intercurrent infection, especially inflammatory, unsolved since less than one month,
  • Patients with clinical signs of heart failure or hospitalized for cardiac decompensation during the past 12 months,
  • Patients with left ventricular ejection fraction < 50%, pulmonary arterial hypertension with tricuspid regurgitation velocity > 2.5 m/s, atrial fibrillation, ventricular rhythm disorders during exercise, left ventricular hypertrophy (septal to lateral wall thickness ≥ 10 mm), significant valvulopathy, established coronary disease, uncontrolled hypertension,
  • Patients with a treatment against cardiac arrhythmia or altering sino-atrial node activity (beta-blockers, atropine, sympathomimetic agents…),
  • Patients under anti-coagulant treatment,
  • Patients with pacemaker or defibrillator,
  • Body Mass Index (BMI) > 35,
  • Patients with hip osteonecrosis,
  • Patients with cerebral vasculopathy or history of stroke (cerebrovascular attack) with epilepsy,
  • Pregnant or lactating patients,
  • Homeless patients,
  • Patients with the inability to understand the aims,

Treatment and study plan

Training program

Other

Each training session will last 45 min. Exercise will start by a 5-min warm-up cycling period, followed by 30 min of cycling at the power output (W) individually determined before and corresponding to the first lactate threshold corresponding approximately to 2.5 mmol/l . Then patients will cool down for 5 min. Finally, the training sessions will end by 5 min of light stretching. All training sessions will take place at the hospital and will be under the supervision of a physician. Heart rate, oxygen saturation and blood lactate concentrations will be regularly measured. Work rate will be adjusted according to the obtained results. As a safety procedure, blood lactate concentration must not exceed 4 mmol/L during the training sessions. A particular attention will be paid to the hydration of patients. Pain and fatigue will be evaluated everyday by the patients using (100 mm) visual analog scales.

Primary outcomes

  1. Power output (W) associated with the 4 mmol/L blood lactate concentration

    Time frame: 8 weeks

    The blood lactate concentration curve in response to incremental exercise depends on the physical ability of patients. Endurance training is known to increase the power output (W) associated with a given blood lactate concentration. For the present study, we used the 4 mmol/L blood lactate concentration as a remarkable/singular point of the curve

Secondary outcomes

  1. Muscle fiber types distribution (%)

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  2. perimeter (µm) of muscle fiber

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  3. surface area (µm2) of muscle fiber

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  4. satellite cell account

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  5. Creatine Kinase (CK) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  6. Phosphofructokinase (PFK) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  7. Citrate Synthetase (CS) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  8. HAD (µmol/min/g dry muscle) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  9. COx (arbitrary unit, a.u.) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  10. Lactate Dehydrogenase (LDH) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  11. isoforms (%) of muscle

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  12. Number of capillaries per mm2 (capillary density) and in contact with a muscle fiber

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  13. surface area of microvessels (µm2)

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  14. diameter of microvessels (µm)

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  15. capillary tortuosity (quotient)

    Time frame: 8 weeks

    Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).

  16. expired volume (VE)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  17. oxygen consumption (VO2)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  18. carbon dioxide production (VCO2) (L/min)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  19. respiratory quotient (QR)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  20. Heart Rate (HR) (min-1)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  21. lactate level (mmol/l) at the end of submaximal incremental exercise

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  22. Pulmonary volumes (L)

    Time frame: 8 weeks

    The volumes are measured by plethysmography

  23. Performance to the six minute walk test (m)

    Time frame: 8 weeks

  24. Index of muscular blood flow and tissular oxygenation at rest (%)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  25. Index of exercise using Near-infrared reflectance spectroscopy (NIRS) (%)

    Time frame: 8 weeks

    Patients will perform a submaximal incremental exercise on a cycle ergometer. Exercise will start at 20 W and 30 W for females and males, respectively. After 2 minutes at this load, and every 2 minutes thereafter, work rate will increase by 10 W and 15 W for females and males, respectively. Total exercise duration is expected to be within 8 to 14 minutes.

  26. Maximal voluntary contraction (N)

    Time frame: 8 weeks

    Maximal Voluntary Contraction (MVC) will be measured 3 times 1 min apart to determine an initial MVC. After 10 min of rest following the MVC trials, neuromuscular fatigability will be assess by repetition of series of 10 submaximal contractions (of 4 s separated by 5 s) followed by a MVC trial until a decrease of 25% of the initial MVC is observed. No more than 7 series will be performed, even if the 25% decrease of initial MVC is not observed.

  27. Neuromuscular fatigability (%)

    Time frame: 8 weeks

    It is measured in the same time that MVC

  28. Quality of life : Scores to the Short Form 36 (SF-36)

    Time frame: 8 weeks

  29. Quality of life : Functional Assessment of Cancer Therapy (FACT Fatigue Part)

    Time frame: 8 weeks

  30. Quality of life : State-Trait Anxiety Scale (STAI Y-A)

    Time frame: 8 weeks

  31. Quality of life : Physical Self-Description Questionnaire( PSDQ)

    Time frame: 8 weeks

  32. Complete blood count and biochemical analyses (ionogram, urea, creatinine, LDH, creatine phosphokinase (CPK), aspartate aminotransferase ; usual units)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  33. Blood and plasma viscosity (centipoise)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  34. Erythrocyte deformability (%)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  35. aggregation properties (a.u.)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  36. dense red blood cells (%)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  37. Plasma analyses of adhesion molecules and markers of inflammation

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  38. oxidative stress

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  39. NO metabolism (µmol/L)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  40. Activity of antioxidant enzymes (µmol/L/min)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  41. Expression of erythrocytes membrane proteins (u.a.)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  42. Red blood cell (RBC) adhesion to endothelial cells (count of adhering RBC /mm²)

    Time frame: 8 weeks

    Patients will be subjected to blood samplings

  43. Various hemodynamic criteria using echocardiography at rest and exercise

    Time frame: 8 weeks

  44. vaso-occlusive crises and acute chest syndrome

    Time frame: 8 weeks

    During the 8 weeks, all vaso-occlusive crises and acute chest syndrome will be collected

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Saint Etienne

Other

Collaborators

  • Centre de Référence des Syndromes Drépanocytaires Majeurs
  • Claude Bernard University
  • Laboratoire de Physiologie de l'Exercice

Registry information

Official study title

Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients: Benefits on Physical Ability and Skeletal Muscle. An Interventional Pilot, Multicentric, Prospective, Longitudinal Study

Acronym: EXDRE

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Oct 8, 2015
Registry last updated
Sep 13, 2021

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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