Clinical trial NCT01748370: Vitamin D Treatment and Hypogonadism in Men
Official title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Effects of Vitamin D Supplementation on Androgen Levels in Hypogonadal Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypogonadism
Keywords: vitamin D
hypogonadism
testosterone
intervention
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2012-12-12
Enrollment: 200
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Total testosterone (TT)
timeFrame: Change from baseline in TT at 12 weeks
Secondary outcomes:
measure: Free testosterone (FT)
timeFrame: Change from baseline in FT after 12 weeks
measure: Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR)
timeFrame: Change from baseline in HOMA-IR at 12 weeks
measure: Lipid levels (total cholesterol)
timeFrame: Change from baseline in total cholesterol at 12 weeks
measure: Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc
timeFrame: Change from Baseline in AUCgluc at 12 weeks
measure: Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCins
timeFrame: Change from Baseline in AUCins at 12 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Metabolism
Study officials:
affiliation: Medical University of Graz
name: Elisabeth Lerchbaum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lerchbaum E, Pilz S, Trummer C, Schwetz V, Pachernegg O, Heijboer AC, Obermayer-Pietsch B. Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4292-4302. doi: 10.1210/jc.2017-01428.