Vitamin D Treatment and Hypogonadism in Men

Study Overview
=================
Brief Summary
-----------------
Low total testosterone (TT) is present in about 30% of men aged >60 years and in up to 7% of younger men. Male hypogonadism is associated with metabolic and cardiovascular diseases as well as with increased mortality. There is evidence showing a relationship of TT with vitamin D in men. We aim at evaluating the effect of vitamin D supplementation on TT and metabolic parameters in hypogonadal men. We will study the effects of 20,000 IU vitamin D weekly in a 12 wk randomized, double-blind, placebo-controlled trial in 100 men with TT <3.0 ng/ml and 25-hydroxyvitamin D (25(OH)D) <30 ng/ml (patients) as well as in 100 men with TT ≥3.0 ng/ml and 25(OH)D <30 ng/ml (controls). Vitamin D supplementation might be a safe therapeutic approach improving TT levels as well as metabolic parameters in hypogonadal men. Further the effects of vitamin D on androgens will be evaluated in eugonadal men.

Official Title
-----------------
A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Effects of Vitamin D Supplementation on Androgen Levels in Hypogonadal Men

Conditions
-----------------
Hypogonadism

Intervention / Treatment
-----------------
* Drug: Vitamin D supplementation in hypogonadal men
* Drug: Vitamin D supplementation in eugonadal men
* Drug: Placebo hypogonadal
* Drug: Placebo eugonadal


Participation Criteria
=================
Eligibility Criteria
-----------------
Hypogonadal men: Inclusion Criteria: 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 <70 years Written informed consent before entered into study 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) Eugonadal men: Inclusion Criteria: TT levels ≥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 <70 years Written informed consent before entered into study 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, 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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D hypogonadal<br>Vitamin D supplementation in hypogonadal men | Drug: Vitamin D supplementation in hypogonadal men<br> <br> * Other names: A11CC05 Colecalciferol;|
| Experimental: Vitamin D eugonadal<br>Vitamin D supplementation in eugonadal men | Drug: Vitamin D supplementation in eugonadal men<br> <br> * Other names: A11CC05 Colecalciferol;|
| Placebo Comparator: Placebo hypogonadal<br>Vitamin D supplementation in hypogonadal men | Drug: Placebo hypogonadal<br> <br> |
| Placebo Comparator: Placebo eugonadal<br>Vitamin D supplementation in eugonadal men | Drug: Placebo eugonadal<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total testosterone (TT) |  | Change from baseline in TT at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free testosterone (FT) |  | Change from baseline in FT after 12 weeks | 
| Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR) |  | Change from baseline in HOMA-IR at 12 weeks | 
| Lipid levels (total cholesterol) |  | Change from baseline in total cholesterol at 12 weeks | 
| Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc |  | Change from Baseline in AUCgluc at 12 weeks | 
| Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCins |  | Change from Baseline in AUCins at 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin D, hypogonadism, testosterone, intervention