2020 Fiscal Year Research-status Report
Physical activity in patients with sickle cell disease: Effect on the vascular function, frequency of painful episodes and clinical course of the disease
| Project/Area Number |
19KK0248
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| Research Institution | Ochanomizu University |
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Principal Investigator |
tripette julien お茶の水女子大学, 文理融合 AI・データサイエンスセンター, 准教授 (30747481)
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| 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)
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| Project Period (FY) |
2019-10-07 – 2024-03-31
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| Keywords | sickle cell disease / physical activity / objective measurement / pain / vascular adaptation / Africa / blood viscosity / vaso occlusive crisis |
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| Outline of Annual Research Achievements |
In order to prevent morbid vascular complications, sickle cell disease (SCD) patients are usually recommended to avoid physical exercise. However, clinical complications have never been studied relatively to the level of objectively measured physical activity (PA).
We are investigating PA in a cohort of African SCD patients. We are also evaluating the severity of the disease, the frequency of painful vaso-occlusive crises (VOC), as well as a number of biomarkers and vascular parameters. To date, 33 patients have been included in the protocol. The baseline experimental trial consists in monitoring daily PA, pain and clinical events during a 4-6 week period. Inactive subjects participate to a 2-month longitudinal protocol that includes a pedometer intervention and monthly follow-up visits.
At baseline, subject-average daily step-count data are distributed from 4316 to 24783 steps. Beneficial vascular adaptations (pulse wave velocity indexes) have been noted for the most active ones. Subjects making a minimum of 53 min of moderate to vigorous PA per day also showed a significantly higher heart rate variability. However, patients performing regular vigorous exercises have a significantly higher baseline blood viscosity. They experienced more intense pain during the observation period and had more VOC during the previous year.
For the first time, data showed moderate PA can be associated with beneficial vascular adaptations in SCD patients. However, these alterations may not be sufficient to balance the deleterious hemorheological context favored by regular vigorous exercises.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
While, the beginning of experiment, initially scheduled in early 2020, has been delayed several times due to the evolutions of the COVID-19 pandemic, the work is now progressing “rather smoothly”. Subjects are now recruited at a normal rate since January 2021. To date, 33 patients have been included in the protocol. 27 of them completed the baseline experimental period. 13 inactive subjects completed (/are completing) the longitudinal protocol. Patients are recruited once every 2 weeks at the Centre National de Transfusion Sanguine, Senegal. Only one subject dropped out before the end of the baseline experimental period. We have found that the logistic capacity of the team allows managing between 12-15 subjects at a time. Consequently, experimental visits are scheduled every weeks. We have found the Dakar cohort to be more active than expected. The inclusion of inactive patients in the intervention protocol is therefore progressing at a lower rate.
The parameters of interest can be classified in 3 categories. 1) Some parameters, such as activity outcomes, are treated on a daily basis. They are necessary to the daily management of the study. 2) Some parameters are treated during (or immediately) after the experimental visits. They include the hemorheological parameters, heart rate variability outcomes, pain diary record entries, etc. 3) Some measurements will be done at larger intervals, so that enough samples can be collected before performing the tests. This category includes most of the bio-markers.
The protocol has been registered to the UMIN Clinical Trials Registry.
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| Strategy for Future Research Activity |
The main objective is to increase the number of subjects. We would like to complete baseline measurements for 80-100 subjects by the end of 2021. At the end of the baseline period, subjects presenting a median daily step-count lower than 9000 steps are considered “inactive”. Given the current ratio of inactive/active patients, we can expect 30-40 subjects to be included in the longitudinal follow-up arms before the end of 2021. Longer term goals to be reached by the end of the funding period are 150-200 subjects for the baseline trial, and 50-60 inactive subjects for the 2-month longitudinal trial.
Another important milestone of 2021 is related to the completion of the first biomarker measurements. The tests will be performed at the research facilities of Lyon 1 University, France. A ~4.000.000 JPY budget will be allocated to this task.
In addition, the treatment of secondary outcomes (e.g. GPAQ and SF36) will start. Eventually, a total of >150 parameters will be available for each subject at each experimental visit.
Finally, the Japanese team is willing to travel to Senegal and France to assist their Senegalese and French partners with the data collection and treatment flow, and to discuss the progresses of the data analysis. Research meetings will be scheduled as soon as the evolution of the COVID-19 allows international travels.
The current progresses in the analysis of baseline measurements point to several significant results and original findings, which could be disseminated to the community before the end of the experimental period.
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| Causes of Carryover |
The amount of 2019 and 2020 transferred to 2021 will be used to complete tasks that have been delayed due to the outbreak of the COVID-19 pandemic. These task mainly consists in the two followings:
1) Travels and scientific visits to assist our international partners with the data collection and processing flow. Progresses related to the data analysis, protocol adaptations and possible scientific communications (conferences, articles) will also be discussed. Meeting with our Senegalese and French colleagues is necessary to secure a long-term partnership and continue studying topics related to physical activity in West Africa in the future.
2) Complete tasks related to the measurements of biomarkers. This includes bioassays for measuring the blood concentration of inflammatory agents, vascular adhesion molecules and micro-particles. This markers are absolutely necessary to assessing the vaso-occlusive risks and the effect of physical activity in sickle cell disease patients. In 2021, a large amount of the budget will be directed to purchasing the antibodies and consumables necessary to the completion of these measurements (~4.000.000 JPY if considering the current exchange rate).
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Research Products
(3 results)
