Assessing the Effects of Alfacalcidol Intake on Expression of Involed Gene in Metabolism in Obese Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Tehran University of Medical Sciences
Sponsor:
Information provided by (Responsible Party):
Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT01752244
First received: December 14, 2012
Last updated: December 24, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention
Obesity
Dietary Supplement: Placebo
Dietary Supplement: Alfacalcidol

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Change of weight [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]
    measurement with Body composition device


Other Outcome Measures:
  • Body mass index change [ Time Frame: Change from baseline to 8 weeks ] [ Designated as safety issue: No ]
    calculated with BMI equation


Estimated Enrollment: 94
Study Start Date: January 2012
Estimated Study Completion Date: January 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alfacalcidol
Alfacalcidol
Dietary Supplement: Alfacalcidol
Alfacalcidol
Other Names:
  • One-Alpha® Capsules 1 microgram
  • alfacalcidol
  • 1-α hydroxyvitamin D3
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
Other Names:
  • corn oil capsule
  • Corn oil Pearl

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   22 Years to 52 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Age 22-52 years Body mass index equal or more than 30

Exclusion criteria:

Acute or chronic inflammatory disease History of hypertension Alcohol or drug abuse History of any condition affecting inflammatory markers such as known cardiovascular disease Thyroid diseases Malignancies Current smoking Diabetes mellitus Sustained hypertension Heart failure Acute or chronic infections Hepatic or renal diseases Use of PPARγ agonist drug

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01752244

Contacts
Contact: Arash Hossein-nezhad, MD, PHD arashh@bu.edu
Contact: Khadijeh Mirzaei, MS mirzaei_kh@razi.tums.ac.ir

Locations
Iran, Islamic Republic of
TehranUMS Recruiting
Tehran, Iran, Islamic Republic of
Contact: Arash Hossein-nezhad, MD, PhD       arashh@bu.edu   
Contact: Khadijeh Mirzaei, MS       mirzaei_kh@tums.ac.ir   
Principal Investigator: Arash Hossein-nezhad, MD, PhD         
Sub-Investigator: Khadijeh Mirzaei, Ms         
Sponsors and Collaborators
Tehran University of Medical Sciences
Investigators
Principal Investigator: Arash Hossein-nezhad, MD, PhD Tehran University of Medical Sciences
Principal Investigator: Khadijeh Mirzaei, Ms Tehran University of Medical Sciences
  More Information

No publications provided by Tehran University of Medical Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT01752244     History of Changes
Other Study ID Numbers: 91-02-27-18041
Study First Received: December 14, 2012
Last Updated: December 24, 2012
Health Authority: Iran: Ethics Committee

Keywords provided by Tehran University of Medical Sciences:
Obesity, vitamin D analogue, VDR, PPARg, PGC1a

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hydroxycholecalciferols
1-hydroxycholecalciferol
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 24, 2014