Male hypogonadism (total testosterone <3ng/ml) MedDRA version: 14.1 Level: HLT Classification code 10000193 Term: Male sex hormone abnormalities System Organ Class: 100000004872
Conditions
Interventions
Trade Name: Oleovit D3 Tropfen
Pharmaceutical Form: Oral drops
INN or Proposed INN: Colecalciferol
Other descriptive name: CHOLECALCIFEROL CONCENTRATE (WATER-DISPERSIBLE FORM)
Concentration unit: IU/m
Sponsors
Medizinische Universität Graz, Innere Medizin
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Hypogonadal men: - TT levels below 3.0 ng/ml (measured at the baseline visit and confirmed at study visit 1) - 25(OH)D levels below 30 ng/ml (measured at the baseline visit) - Male, age of = 18 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Hypercalcemia defined as a serum calcium > 2,7 mmol/L - Oral or transdermal testosterone supplementation in the last 2 months before entering the study - IM testosterone supplementation 6 months before entering the study - Regular intake of vitamin D supplements before study entry - Men with chronic diseases (such as diabetes mellitus, thyroid disease, endocrine disturbances in need of treatment (except hypogonadism), or diseases known to interfere with vitamin D intake or very sensitive to vitamin D intake (such as inflammatory disease with granuloma: sarcoidoses, tuberculosis, Mb Wegener, vasculitis, inflammatory bowel disease - Intake of medication influencing metabolic or endocrine parameters (insulin sensitizers, insulin, glucocorticoids,…) in the last 3 months before study entry - PSA >4 ng/ml (or >3 ng/ml in men at high risk for prostate cancer) (see state of the art) - Palpable prostate nodule or induration - Hematocrit >50% - Untreated severe obstructive sleep apnea - Severe lower urinary tract symptoms - Uncontrolled or poorly controlled heart failure - A history of prostate cancer, breast cancer, orchidectomy, chromosomal disorders (e.g. Klinefelter Syndrome)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: In addition, we also aim to test the hypothesis that vitamin D supplementation improves endocrine parameters (e.g. FT, SHBG, LH, FSH, and estradiol), metabolic parameters as well as sexual, physical and psychological symptoms. Moreover, we will evaluate whether vitamin D supplementation with 20,000 weekly over 12 weeks improves endocrine parameters (e.g. TT, FT, SHBG, LH, FSH, and estradiol) and metabolic parameters when compared to placebo in eugonadal men. Further, we will perform genotyping of vitamin D-related polymorphisms to evaluate a possible genetic background of the association of vitamin D with androgen levels. In addition, gene expression analyses of relevant candidate genes in association with pathways of vitamin D and testosterone will be performed at each visit in order to analyze functional changes during vitamin D treatment.;Primary end point(s): Changes in total testosterone levels after vitamin D supplementation. ;Timepoint(s) of evaluation of this end point: 4 weeks, 12 weeks;Main Objective: The primary objective is to evaluate whether vitamin D supplementation with 20,000 weekly over 12 weeks significantly increases TT levels when compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in - Endocrine parameters including FT, SHBG, LH, FSH, and estradiol - Insulin resistance and insulin sensitivity assessed by homeostatic model assessment-insulin resistance (HOMA-IR), HOMA-beta, MATSUDA, and Quantitative Insulin-sensitivity Check Index (QUICKI) - AUCins and AUCgluc derived from the oral glucose tolerance test - Lipid levels (total cholesterol, HDL, LDL, triglycerides) - Fat and lean mass assessed via dual-energy X-ray absorptiometry (DXA) - Sexual, physical and psychological symptoms after vitamin D supplementation. Moreover, we will perform genotyping of vitamin D-related polymorphisms (VDR Cdx-2, Bsm-I, Fok-I, Apa-I, Taq-I, GC, DHCR7 and CYP2R1). In addition, gene expression analyses will be done for biosynthesis and metabolism of male (and female) sex hormones, e.g. androgen receptor (AR), estrogen receptor (ER), aromatase (Cyp19A1), FOXL2 (Forkhead Box Protein L2), hydroxysteroid dehydrogenase 3ß (HSD3ß), STAR (Steroidogenic acute regulatory protein), Cytochrom-P11 (CYP11), cytochrome P17 (CYP17A1), receptors for follicle stimulating hormone (FSHR) and luteotropic hormone (LHR), SHBG (Sex-hormon binding globulin),…), important anti- and proinflammatoric genes (interleukins, interferon, FOXP3 (forkhead box P3),…), genes of glucose metabolism (IGF-1 (Insulin-like growth factor 1), IGF-1R (Insulin-like growth factor 1 Rezeptor), IGF-BP (Insulin-like growth factor binding proteins), INSL (Insulin-like peptides), insulin rezeptor (IR),…), genes of the vitamin D metabolism (vitamin D rezeptor (VDR), 25-Hydroxylasen (Cyp2R1, Cyp27A1), 24-Hydroxylase (Cyp24A1), 1-alpha-hydroxylase (Cyp27B1),…), genes of the TGF-beta superfamily (inhibins, activins and their receptos, follistatin, transforming growth factors (TGF) and their receptors, bone morphogenetic proteins (BMPs), anti müllerian hormone (AMH), growth and differentiation factor 9 (GDF9),…), as well as genes out ofbone metabolism, such as parathyrin (PTH), klo | — |
Countries
Austria
Contacts
Public ContactKlinische Studien Information
Medizinische Universität Graz
Outcome results
None listed