Physical Exercise as a Sustainability Tool in Men With Dysmetabolic Hypogonadism

Study Overview
=================
Brief Summary
-----------------
Aim of this project is to delineate sustainable physical exercise programs and to assess the effects of such programs mainly on endocrine-metabolic and neurovegetative outcomes in a cohort of men with metabolic syndrome-related late-onset central hypogonadism. Participants will undergo a personalised exercise program. After 6 months they will be subdivided into two groups, according to the weekly physical activity volume actually performed (above or below 600 MET·minutes/week). Changes in endocrine-metabolic and neurovegetative outcomes will be compared between the two groups.

Official Title
-----------------
Physical Exercise as a Sustainability Tool in Men Affected With Metabolic Syndrome-related Late-onset Central Hypogonadism: Role of Endocrine-metabolic and Neurovegetative Outcomes

Conditions
-----------------
Hypogonadism, Male, Metabolic Syndrome, Autonomic Imbalance, Life Style, Healthy, Physical Inactivity

Intervention / Treatment
-----------------
* Behavioral: Structured and personalized program of physical exercise


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosis of late-onset central hypogonadism: total T levels < 8 nmol/L (or < 12 nmol/L in the presence of calculated free T < 225 pmol/L) combined with sexual symptoms (erectile dysfunction, low libido and loss of waking erections) [12]; diagnosis of metabolic syndrome, defined as association of waist circumference (WC) > 94 cm and at least two among the following criteria: triglycerides ≥ 150 mg/dl, HDL-C < 40 mg/dl, glucose > 100 mg/dl, blood pressure (BP) ≥ 130/85 mmHg [33]; ability to give informed consent, in accordance with good clinical practice rules and applicable national laws. Exclusion Criteria: History of hypothalamus-pituitary organic disorders and/or testicular diseases; impossibility to assess cardiac autonomic regulation due to arrhythmias and/or current treatment for heart rate (HR) control (e.g., beta-blockers, antiarrhythmics); impossibility to undergo clinical assessment; impossibility or contraindications to perform exercise program (for instance, psychiatric disorders, severe musculoskeletal diseases, arrhythmias); inability to give informed consent or unwillingness to be enrolled in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: weekly physical activity volume performed above 600 MET·minutes/week<br>Exercise program requiring clear definition of modality, intensity, frequency, duration and progression of exercise, tailored on patient's clinical conditions and goals. | Behavioral: Structured and personalized program of physical exercise<br>* In line with the most recent guidelines, exercise prescription will require the clear definition of modality, intensity, frequency, duration and progression of exercise, tailored on patient's clinical conditions and goals. This intervention will be accompanied by a nutrition program aiming for proper dietary habits in terms of both quantity and quality.<br>|
| Other: weekly physical activity volume performed below 600 MET·minutes/week<br>Exercise program requiring clear definition of modality, intensity, frequency, duration and progression of exercise, tailored on patient's clinical conditions and goals. | Behavioral: Structured and personalized program of physical exercise<br>* In line with the most recent guidelines, exercise prescription will require the clear definition of modality, intensity, frequency, duration and progression of exercise, tailored on patient's clinical conditions and goals. This intervention will be accompanied by a nutrition program aiming for proper dietary habits in terms of both quantity and quality.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in hypothalamic-pituitary-gonadal axis function | particularly testosterone levels (nmol/l) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition | percentage of fat mass and free fat mass | 6 months | 
| Change in serum skeletal isoenzyme of alkaline phosphatase | Change in serum skeletal isoenzyme of alkaline phosphatase concentration (ug/l) | 6 months | 
| Change in C-terminal telopeptide of type I collagen | Change in C-terminal telopeptide of type I collagen concentration (ng/l) | 6 months | 
| Change in erythrocyte sedimentation rate | Change in erythrocyte sedimentation rate (mm/h) | 6 months | 
| Change in C-reactive protein | Change in C-reactive protein concentration (mg/l) | 6 months | 
| Change in total cholesterol | Change in total cholesterol concentration (mg/dl) | 6 months | 
| Change in HDL cholesterol | Change in HDL cholesterol concentration (mg/dl) | 6 months | 
| Change in triglycerides | Change in triglycerides concentration (mg/dl) | 6 months | 
| Change in glucose profile | glycemia (mg/dl) | 6 months | 
| Change in kidney function | creatinine (mg/dl) | 6 months | 
| Change in aspartate aminotransferase | Change in aspartate aminotransferase concentration (U/L) | 6 months | 
| Change in alanine aminotransferase | Change in alanine aminotransferase concentration (U/L) | 6 months | 
| Change in cardiac autonomic regulation | Autonomic Nervous System Index (ANSI) | 6 months | 
| Change in nutrition quality | American Heart Association (AHA) Diet Score | 6 months | 
| Change in perception of stress, fatigue, and somatic symptoms | short version of 4SQ questionnaire considering 4 specific symptoms (total score ranging from 0 to 40) | 6 months | 
| Change in weekly physical activity volume | short version of International Physical Activity Questionnaire, which focuses on intensity (nominally estimated in Metabolic Equivalents - MET - according to the type of activity) and duration (in minutes) of physical activity. The following levels will be considered: brisk walking (≈ 3.3 METs), other modalities of activity of moderate intensity (≈ 4.0 METs), and activities of vigorous intensity (≈ 8.0 METs). | 6 months |