Clinical Trial: Evaluation of a Training Program for Homozygous Sickle Cell Disease Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary: 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.
Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Current Primary Outcome: Power output (W) associated with the 4 mmol/L blood lactate concentration [ Time Frame: 8 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Muscle fiber types distribution (%) [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• perimeter (µm) of muscle fiber [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• surface area (µm2) of muscle fiber [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• satellite cell account [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• Creatine Kinase (CK) of muscle [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• Phosphofructokinase (PFK) of muscle [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• Citrate Synthetase (CS) of muscle [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• 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).
• 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).
• Lactate Dehydrogenase (LDH) of muscle [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• isoforms (%) of muscle [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• 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).
• surface area of microvessels (µm2) [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• diameter of microvessels (µm) [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• capillary tortuosity (quotient) [ Time Frame: 8 weeks ]
  Patients will be subjected to a biopsy of the vastus lateralis muscle (≈ 200 mg).
• 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.
• 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.
• 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.
• 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.
• Heart Rate (HR) (min-1) [ Time Frame: 8 weeks&
  
  

  Original Secondary Outcome: Same as current
  
  Information By: Centre Hospitalier Universitaire de Saint Etienne
  

  Dates:
  Date Received: August 25, 2015
  Date Started: September 2014
  Date Completion:
  Last Updated: April 8, 2016
  Last Verified: April 2016