Assessing the Effects of Alfacalcidol Intake on Expression of Involed Gene in Metabolism in Obese Subjects
Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the insulin resistance. Moreover, we will evaluate the pathways of Vitamin D receptor (VDR), Peroxisome proliferator-activated receptor gamma (PPARγ) and eroxisome proliferator-activated receptor- coactivator-1 α (PGC1α) gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Assessing the Effects of Supplementary Alfacalcidol Intake on Peroxisome Proliferator-activated Receptor-coactivator-1α, Vitamin D Receptor and Peroxisome Proliferator-activated Receptor Gamma Gene Expression in Obese Subjects|
- Expression of VDR, PPARγ and PGC1α gene [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]measurement of Relative gene expression with RT-PCR.
- Change of weight [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]measurement with Body composition device
- Body mass index change [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]calculated with BMI equation
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||January 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Dietary Supplement: Alfacalcidol
Placebo Comparator: Placebo
Corn oil pearl Capsules 1 gram: were given to the intervention group once a day for 8 weeks
Dietary Supplement: Placebo
corn oil Capsules 1 gram: were given to the placebo group once a day for 8 weeks
Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance. The anti-inflammatory characteristics of vitamin D have been demonstrated in previous studies. In addition to its role in bone and calcium metabolism, vitamin D is demonstrated to be influential in the regulation of different immune system functions and glucose homeostasis pathways. Although low levels of vitamin D have shown to be in close correlation with obesity, whether vitamin D deficiency is the cause or the consequence of obesity remains unclear. It is noteworthy that several studies have demonstrated that vitamin D deficiency is associated with an increased resistance to insulin.
The biologic effects of vitamin D are primarily mediated via the nuclear transcription factor, vitamin D receptor (VDR), which triggers the expression of vitamin D responsive genes. VDR is expressed on different immune cells such as monocytes, T-lymphocytes, and granulocytes. It is documented that VDR and PGC-1α show an overlapping pattern of expression. Furthermore, as the expression of PGC-1α and PPARγ are regulated via environmental stimuli such as diet, it could be suggested that the function of VDR function can also be altered in response to external stimuli. PGC-1α was demonstrated to be of a particular importance in amelioration of increased insulin sensitivity.
Accordingly, to evaluate whether alphacalcidol treatment in obese subjects who generally suffer from a low state chronic inflammation could affect the insulin resistance, we designed the current double blind clinical trial study to compare the effect of alfacalcidol with placebo on serum glucose, 25-OH vitamin D, PTH, and lipid profile levels as well as Homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) indexes as a markers of insulin resistance. Furthermore, to assess the possible cross talk between VDR and PPARγ, the gene expressions of these VDR, PPARγ and PGC1α were evaluated following a course of treatment with either alphacalcidol or placebo.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01752244
|Contact: Arash Hossein-nezhad, MD, PHDfirstname.lastname@example.org|
|Contact: Khadijeh Mirzaei, MSemail@example.com|
|Iran, Islamic Republic of|
|Tehran, Iran, Islamic Republic of|
|Contact: Arash Hossein-nezhad, MD, PhD firstname.lastname@example.org|
|Contact: Khadijeh Mirzaei, MS email@example.com|
|Principal Investigator: Arash Hossein-nezhad, MD, PhD|
|Sub-Investigator: Khadijeh Mirzaei, Ms|
|Principal Investigator:||Arash Hossein-nezhad, MD, PhD||Tehran University of Medical Sciences|
|Principal Investigator:||Khadijeh Mirzaei, Ms||Tehran University of Medical Sciences|