ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients (EXDRE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02571088
Recruitment Status : Completed
First Posted : October 8, 2015
Last Update Posted : April 11, 2016
Sponsor:
Collaborators:
Centre de Référence des Syndromes Drépanocytaires Majeurs
Laboratoire de Physiologie de l’Exercice
Claude Bernard University
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Sickle Cell Hemoglobin C Disease Hemoglobin S Disease Other: Training Program Not Applicable

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : September 2014
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016


Arm Intervention/treatment
Experimental: Training Program
The treatment will consist in an endurance training program. Only patients of the trained group will be subjected to this training program which will typically consist in 3 training sessions per week during 8 weeks i.e., 24 training sessions. Each training session will last 45 min. All training sessions will take place at the hospital and will be under medical supervision.
Other: Training Program
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.

No Intervention: No Training Program
It will be asked to the control patients to not change their habitual physical activity during the entire period of observation



Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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,

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02571088


Locations
France
Hopital Avicenne
Bobigny, France, 93000
Centre hospitalier sud francilien
Corbeil-essonnes, France, 91100
CHU Henri MONDOR
Creteil, France, 94010
CHU Kremlin-Bicêtre
Le Kremlin Bicetre, France, 93270
Hopital Europeen Georges POMPIDOU
Paris, France, 75015
Hopital Necker
Paris, France, 75015
Hopital Tenon
Paris, France, 75020
Centre hospitalier de Saint-Denis
Saint-denis, France, 93200
CHU de SAINT-ETIENNE
Saint-etienne, France, 42000
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Centre de Référence des Syndromes Drépanocytaires Majeurs
Laboratoire de Physiologie de l’Exercice
Claude Bernard University
Investigators
Principal Investigator: Leonard FEASSON, MD CHU de SAINT-ETIENNE
Study Director: Laurent MESSONIER, PhD Université de Savoie

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT02571088     History of Changes
Other Study ID Numbers: 1408030
2014-A00334-43 ( Other Identifier: ANSM )
First Posted: October 8, 2015    Key Record Dates
Last Update Posted: April 11, 2016
Last Verified: April 2016

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Sickle Cell Hemoglobin C Disease
Sports Training
Hemoglobin S Disease
Lactate

Additional relevant MeSH terms:
Anemia, Sickle Cell
Sickle Cell Trait
Hemoglobin C Disease
Hemoglobin SC Disease
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn