Physical activity in patients with sickle cell disease: Effect on the vascular function, frequency of painful episodes and clinical course of the disease

Research Project

Project/Area Number	19KK0248
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research Institution	Ochanomizu University
Principal Investigator	tripette julien お茶の水女子大学, 生活科学部, 学部教育研究協力員 (30747481)
Co-Investigator(Kenkyū-buntansha)	吉田司国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所, 研究員 (20822175) 宮地元彦国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所身体活動研究部, 部長 (60229870)
Project Period (FY)	2019-10-07 – 2023-03-31
Project Status	Granted (Fiscal Year 2019)
Budget Amount *help	¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000) Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000) Fiscal Year 2020: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000) Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords	sickle cell anemia / physical activity / Africa / pilot study / pain diary / accelerometer / quality of life / sickle cell disease / pain / intervention study / vascular physiology
Outline of Research at the Start	Sickle cell disease is a group of genetic blood disorders with fatal complications, which is mostly prevalent in Africa, Europa and the Americas. This research aims at establishing exercise guidelines to improve the quality of life of patients, in particular those living in developing countries.
Outline of Annual Research Achievements	Sickle cell anemia is associated with an important morbidity. 80% of the patients are living in Sub-Saharan Africa. The current medical practice recommends a strict avoidance of physical exercise. However, recent works conducted in transgenic sickle mice indicate that the patients could benefit from the physical activity-induced vascular adaptations. The present project is the first attempt to test the effect of physical activity in a population of sickle cell disease patients. The study is conducted in a cohort of patients living in Sub-Saharan Africa. In order to evaluate the feasibility of the method in a clinical center located in Sub-Saharan Africa and the adherence of patients to a research protocol that requires reporting data on the daily, 4 sickle cell disease patients have been through a procedure that resembles to the baseline protocol of the proposed study design. The patients worn a physical activity monitor for 2 months and returned it without any data loss. They also returned they diary pain questionnaire without any missing data. According to physical activity monitor data and answer to the GPAQ questionnaire, the selected patients were moderately active (8715 +/- 1340 steps/day), offering some room to conduct a physical activity intervention. Interestingly, they also experienced a monthly average of 1.5 painful episode. The answers to the SF36 questionnaire on the quality of life indicate heterogeneous levels of general health (35-70%), but a relatively high level of physical functioning (65-95%). The proposed study design seems feasible.
Current Status of Research Progress	Current Status of Research Progress 4: Progress in research has been delayed. Reason The start of the study has been delayed due to the outbreak of the COVID-19 pandemic. The associated sanitary risk does not allow researchers travelling internationally, and prevents the implementation of scientific protocols that would put the subjects at risk and load the local health care facilities. The beginning of the study has been suspended until at least September 2020 (tentatively).
Strategy for Future Research Activity	The main research is not expected to start before September 2020 at the earliest due to the current evolution of the COVID-19 pandemic. In the meantime, the preparation of the study will continue. The research equipment and consumables necessary to the implementation of the trial will be purchased and tested. Patients will be recruited during their routine visit to the National Center for Blood Transfusion, Dakar, Senegal. In the best-case scenario, the first subjects included in the longitudinal arm of the study will be able to complete the ~3-month protocol by the first trimester of 2021. Patients who meet the inclusion criteria will be randomized to one of the three followings: 1) intervention group consisting in a 25% increase of the level of physical activity, 2) intervention group consisting in a 50% increase of the level of physical activity, and 3) control group. Subjects who are not eligible to the randomization process will be assigned to the cross-sectional arm of the study. The relationship between 1) physical activity habits, and 2) the clinical course of the disease, vascular function, quality of life will be tested. The researchers from the Japanese side will travel to Dakar in order to participate to the preparation and launch of the study. They will assist the African team for the establishing of an effective and secured data storing and transmission protocol. Depending on the progress of the study, some reagents maybe purchased in order to test blood markers that may not be covered routinely by the National Center for Blood Transfusion.