Evaluation of effect of hydroxyurea on inflammatory markers and oxidative stress markers among adults with sickle cell disease: A prospective observational study

It is a prospective observational study focusing on evaluation of effect of hydroxyurea on inflammatory markers and oxidative stress markers among adults with sickle cell disease. 30% prevalence of sickle cell carriers reported from central India. In Maharashtra, with a positivity rate of 9%, SCD is most prevalent in tribal populations.

The introduction provides context for the study, detailing the sickle cell disease in adults which is an autosomal recessive disorder results due to point mutation and causing substitution of Adenine by thymine (GAG-GTG) leading to replacement to glutamic acid by valine at 7th position in beta globin chain of haemoglobin resulting in HbS formation.

As there were no evidence showing effect of Hydroxyurea in inflammatory and oxidative stress markers among Indian population. Hence this study will be conducted to evaluate the effect of hydroxyurea on Biomarkers among adults with SCD.

The aims and objectives outlines the study’s primary and secondary objectives. The aim is to evaluate the effect of Hydroxyurea treatment on inflammatory markers and oxidative stress markers among adults with sickle cell disease. The primary objective is to determine the effect of Hydroxyurea on inflammatory markers (TNF-alpha, IL-6) oxidative stress markers (MDA, GSH) from baseline to 6months among adults with sickle cell disease. The secondary objective is to assess the safety/tolerability by measuring HbF% & WBC count and to assess quality of life changes in patients using SF-36 Questionnaire.

In review of literature, various studies are cited, exploring the pathogenesis and complications of sickle cell disease. Hydroxyurea therapy is a crucial part of patient management for SCA and ought to be regarded as standard-of-care. Side effects with hydroxyurea are usually mild. Occasionally Headache, gastrointestinal symptoms including abdominal discomfort and nausea.

The methodology describes study design as prospective observational study will be conducted in tertiary care hospital combined with department of pharmacology and department of Haematology and department of Biochemistry, AIIMS, Nagpur. The study will enrol 30 subjects and the sampling strategy includes recruiting patients meeting the inclusion and exclusion criteria. Patient will be prescribed with Hydroxyurea by Haematologist for 6months with dose as required. After every month (1, 2, 3, 4,5months) telephonic call follow up will be done to the patients to check for compliance (by using pill count).At the end of 6th month patient will be called to OPD in the fasting state and follow up investigations will be done.

Statistical analysis involve tests such as paired t test, Wilcoxon signed rank test chi square test. p<0.05 will be considered statistically significant. The data will be analyzed using SPSS software.

Their primary outcome will be change in inflammatory and oxidative stress markers at baseline and after using hydroxyurea for 6months.Secondary outcome will be association of clinical parameters (Number of VOC, Number of blood transfusions, Number of hospital admissions) with biomarkers (inflammatory and biomarkers) , change in quality of life using SF-36 questionnaire, change in haematological parameters (HbF, HbS, CBC for leucocyte count) with treatment using hydroxyurea  at baseline and 6month, compliance to hydroxyurea and ADR to treatment in the 6 months duration.