Immunomodulatory Vitamin D in Thalassemia
Condition: Thalassemia; Tuberculosis; Vitamin D Deficiency
MeSH terms: Tuberculosis; Thalassemia; Vitamin D Deficiency
Study type: Interventional

Summary: 
      Thalassemia becomes one of global health issue and so does Indonesia. In 2015, more than 7600
      children were diagnosed as this hemoglobin genetic disease wherein anemia and lifetime blood
      transfusion contribute to their morbidity and mortality in Indonesia. Major β-Thalassemia is
      the most common type found. However, along with disease progression and age, iron
      accumulation and dysregulation becomes the most common complication exist. In cellular level,
      this condition results in cell and tissue damage especially immune cells and promotes favor
      condition for siderophilic bacteria such as Mycobaterium tuberculosis (Mtb) to growth
      rapidly. Severe infection becomes the second most cause of death in thalassemia-β major
      patients.

      Tuberculosis (Tb) remains the global health issue especially in developing countries. Based
      on World Health Organization (WHO) report on 2015, Indonesia is the second highest burden of
      TB in the world. Both of adaptive and innate immune system plays important role in Mtb
      recognition and eradication. However, immune cells mechanism and activity in response to Mtb
      infection during iron accumulation condition on thalassemia-β major patients may be altered
      therefore need for further study. Macrophage is an adaptive immune cell, has a pivotal role
      on circulating-iron regulation and serves as Mtb host cell. To understand macrophage activity
      on thalassemia-β major patients can be studied by monocyte characteristic stimulated by Mtb
      antigen and evaluated by its differentiation into three subsets based on CD14 and CD16. Mtb
      antigen presentation is identified by HLA-DR expression on monocyte membrane.

      Vitamin D is one of the most affected micronutrients on major β-thalassemia patients, yet it
      has immunomodulatory effect on immune system. Recent finding of vitamin D receptor (VDR)
      expressed in monocyte strongly convince that vitamin D should be maintained in major
      β-thalassemia patients where it is found lower in these patients. Thus, this original and
      true report aimed to declare that the research activity has finished and the data has been
      elaborated. Future plan is developing the original article based on the research finding
      corroborating the previous knowledge and innovative suggestion for the quality of
      thalassemia.
    

Detailed description: 
      This study was designed as a non-randomized, open label, intervention study and performed at
      the thalassemia clinic of the Hasan Sadikin General Hospital, Bandung, West Java, Indonesia.
      Vitamin D deficiency in the general population is common in Indonesia with a prevalence of
      41% reported in one study1. Sixty children (aged 1 month to 15 years) diagnosed as major
      β-thalassemia confirmed by clinical and hemoglobin electrophoresis who regularly having blood
      transfusion at least once in a month controlled in the clinic, from March - May 2018 were
      recruited prospectively. In addition, children who had ferritin serum >1000 µg/L in the last
      three months were met criteria for enrollment. Children who had tuberculosis or co-infection
      (hepatitis B, hepatitis C, and cytomegalovirus) and sign of acute infection were not eligible
      for enrollment. Informed consent was obtained from parents or child's guardian. Vitamin D
      levels were measured before and after supplementation while identifying their vitamin D
      sufficiency status. Classification of vitamin D sufficiency were used according to The
      Endocrine Society Clinical Practice Guideline, which stated that the level of 25(OH)D of < 20
      ng/ml was considered to be vitamin D deficiency whereas a 25(OH)D of 21-29 ng/ml was
      considered to be insufficient. Then, a sufficient vitamin D was considered when the
      concentration of 25(OH)D was 30 ng/mL or above.2 No healthy control was enrolled to test for
      variability in the laboratory tests over time in this study.

      The intervention provided according to the participants' state of vitamin D sufficiency.
      vitamin D sufficient participants received 800 IU cholecalciferol (syrup containing 400 IU
      cholecalciferol per measuring spoon, Gracia Pharmindo, Indonesia) daily for 8 weeks, while
      those who had insufficient or deficient vitamin D level consumed 2000 IU daily. Compliance
      was systematically monitored using drug monitoring diary evaluated by researchers. Blood
      samples for the study objectives were taken at enrollment and after eight weeks of
      cholecalciferol supplementation during routinely scheduled visits to the clinic. The outcome
      measure was the change in the proportion of monocyte subsets and the expression of
      membrane-bound protein of monocyte consist of CD14, CD16, and HLA-DR.

      All procedures were conducted in accordance with policies of the Faculty of Medicine,
      Universitas Padjadjaran and Hasan Sadikin General Hospital, Bandung, West Java, Indonesia.
      This study was approved by Health Research Ethics Committee of Medical Faculty Universitas
      Padjadjaran Bandung with approval number 50/UN6.KEP/EC/2018. All participants signed a
      written informed consent. All participants signed a written informed consent. This study was
      registered in clinicaltrial.gov
    

Intervention name(s): Cholecalciferol supplementation
Intervention type(s): Dietary Supplement
Intervention description(s): supplementation received by subject according to their vitamin D status: insufficiency or deficiency.
Intervention MeSH terms: Cholecalciferol; Vitamin D
Intervention model: Single Group Assignment
Intervention model description: This study was designed as a non-randomized, open label, intervention study and performed at the thalassemia clinic of the Hasan Sadikin General Hospital, Bandung, West Java, Indonesia.
Masking: None (Open Label)
Primary purpose: Treatment