A double blind randomized clinical trial was conducted on diabetic patients referred to the Shariati hospital diabetes clinic of the Tehran University of Medical Sciences (TUMS). These patients had previously confirmed diabetes type 2, according to the ADA (American Diabetes Association) criteria. The Participants were enrolled to the study based on the following inclusion and exclusion criteria.
Sixty one diabetic patients, between 40–60 years old, under treatment with life style modification and/or oral hypoglycemic agents and no recent inflammatory and infectious process (at least for the past 4–6 weeks and during the study) were included. Patients with chronic disease such as chronic renal failure (serum creatinine ® 270 μmol/L), chronic liver failure and decompensate heart failure were excluded. Other exclusion criteria include: coronary artery bypass graft (CABG), respiratory infectious disease, proliferative retinopathy, pregnant or lactating females, childbearing- aged women without safe contraception methods, diabetic foot ulceration or gangrene, smoking, alcohol abuse, hemoglobin a1c (HgA1C) ® 9%, any type of known drug hypersensitivity, malignancy in breast, liver and genital system, vascular disease, fracture history during the past 3 years and use of multivitamin supplements and other traditional drugs in the previous 4–6 weeks, the use of medications that affect bone metabolism, such as corticosteroids, gonadotropin releasing hormone (GnRH) analogous drugs, anticonvulsant, heparin, aluminum-containing antacids, thyroid hormone, thiazides and supplements containing calcium and other minerals. All patients participating in this study were under a same lifestyle and were matched for the drug they used; and also all the patients received just oral agents (metformin/glybenclamide).
Patients’ inclusion was completely informative and voluntary. After inclusion of each patient, complete explanation was given about the goal of study, probable side effects of the drug and patients’ rights during the research process. Then, written informed consent according to institutional guidelines was obtained before treatment. The study protocol was approved by the Medical Ethics Committee of Medical Sciences/TUMS (code number: 0011).
In this study, sample randomization was based on “Permuted Balanced Block” method by an epidemiologist. Patients were randomly assigned into 2 groups: intervention (n = 31) and control (n = 30). Semelil (Angipars®) was prepared by Pars Roos drug company (Tehran, Iran). In the intervention group, patients received 100 mg of Angipars® capsules twice a day. In the control group, participants received placebo (a non absorbable polymer) with the same dose. All participants were given a similar lifestyle program. The patients were followed for a period of three months.
For the primary assessment, a complete set of evaluations was performed which included:
A complete past medical history of the trial patients and an extensive physical examination were done by a trained physician, a dietary questionnaire completed at the beginning and the end of the study.
Measurement of bone mineral density and reporting T-score and Z-score at the baseline, to be sure if there is a major difference between patients in groups.
Approximately 20 ml blood (after fasting for over 12 hours) was taken from every participant. Blood samples were centrifuged within 3 hours of sampling for 20 minute to obtain serum. Samples were frozen at −80°C and they were immediately sent to the hormone laboratory of Endocrinology and Metabolism Research Institute (EMRI)/ Shariati hospital/ TUMS. Baseline laboratory tests were including a complete blood count, fasting blood sugar, HbA1C, bone alkaline phosphatase, osteocalcin, serum TNF-α, urine calcium and creatinine, urine pyridinoline.
Monthly documentation of patient’s compliance to therapy and acceptance of side effects.
Recording any probable side effects and necessary managements.
The distribution of qualitative variables was assessed by Kolmogorov-Smirnov test. Descriptive statistics, including mean, median frequencies, and percentages, were used to describe the population of study. Mean-Whitney U or T test and Chi-square test was performed for comparing quantitative and qualitative variables between groups respectively. The Analysis of covariance (ANCOVA) test was used for comparison outcomes between case and control group. Data were analyzed with SPSS software version 16 (SPSS Inc, Chicago, Illinois). P-values < 0.05 (2-sided test) were considered statistically significant.