TRT on BPH Hypoganadal MetS Patients. Florence-PROTEST

Sponsor

University of Florence (Other)

Overall Status

Completed

CT.gov ID

NCT02366975

Collaborator

(none)

143

Enrollment

Locations

Arms

Duration (Months)

71.5

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There are many evidences in the literature showing that the metabolic syndrome (MetS) is associated with BPH / LUTS. There are also numerous evidence that hypogonadism is associated with both conditions, thus being one of the most probable pathogenetic factor underlying the association between MetS & BPH / LUTS.

Preliminary evidences from observational clinical studies have shown that treatment with testosterone replacement in hypogonadal patients with MetS reduces the symptoms of lower urinary tract symptoms (LUTS) associated with BPH. Preclinical studies performed by the investigators research group show in an experimental model of metabolic syndrome the occurrence of marked inflammation and tissue remodeling of the prostate gland, which is prevented by treatment with testosterone replacement (Vignozzi et al., 2012). There is therefore a need for a clinical trial to demonstrate the effect of treatment with testosterone replacement in reducing the inflammation of the prostate and its effectiveness in improving the symptoms related to inflammation in patients with prostatic BPH associated with metabolic syndrome and testosterone deficiency .

The aims of the present study is to evaluate the effectiveness of testosterone replacement therapy compared to placebo in reducing signs and symptoms of inflammation of the prostate and LUTS symptoms in hypogonadal patients with metabolic syndrome and BPH who are candidates for radical prostatectomy simple.

For this purpose both clinical (assessment of specific symptoms of prostatitis assessed by questionnaire National Institutes of Health Chronic Prostatitis Symptom Index, NIH-CPSI and assessment of the symptoms of LUTS and questionnaires International Prostate Symptom Score,

IPSS), ultrasound (transrectal ultrasound evaluation of markers of prostatic inflammation:

macrocalcifications, inhomogeneity etc.), biochemical (evaluation of inflammatory cytokines in the semen), urodynamic and histology (histomorphometric and immunohistochemical analysis of samples prostate derived from patients enrolled in the study or not treated with testosterone) scores will be performed. Along with the symptoms and clinical signs of prostate inflammation and LUTS, the effect of testosterone therapy or placebo on penile erection will be also evaluated.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Hyperplasia Lower Urinary Tract Symptoms Hypogonadism	Drug: Testosterone gel 2% Other: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

143 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effectiveness of Testosterone Replacement Therapy (TRT) on Prostatic Gland in Hypogonadal Patients Affected by Benign Prostatic Hyperplasia (BPH) and Metabolic Syndrome (MetS). Florence-PROTEST

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Jan 1, 2017

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Eugonadal patients Patients without hypogonadism has been enrollend but not randomized
Active Comparator: Hypogonadal patients A Patients with hypogonadism has been randomized to testosterone gel solution 2%	Drug: Testosterone gel 2% testosterone gel 2% (50mg/die). Other Names: tostran
Placebo Comparator: Hypogonadal patients B Patients with hypogonadism has been randomized to placebo solution gel	Other: Placebo placebo gel

Arm

Intervention/Treatment

No Intervention: Eugonadal patients

Patients without hypogonadism has been enrollend but not randomized

Active Comparator: Hypogonadal patients A

Patients with hypogonadism has been randomized to testosterone gel solution 2%

Drug: Testosterone gel 2%

testosterone gel 2% (50mg/die).

Other Names:

tostran

Placebo Comparator: Hypogonadal patients B

Patients with hypogonadism has been randomized to placebo solution gel

Other: Placebo

placebo gel

Outcome Measures

Primary Outcome Measures

NIH-CPSI [6 months before surgery]
Evaluation in hypogonadal patients with both BPH and metabolic syndrome of the effectiveness of 6 months of treatment with testosterone compared with placebo in improving symptoms of prostatitis and the symptoms of LUTS
IPSS [6 months before surgery]
Evaluation in hypogonadal patients with both BPH and metabolic syndrome of the effectiveness of 6 months of treatment with testosterone compared with placebo in improving symptoms of prostatitis and the symptoms of LUTS

Secondary Outcome Measures

ultrasound prostate characteristics [6 months before surgery]
Evaluation in hypogonadal patients with both BPH and metabolic syndrome of the effectiveness of 6 months of treatment with testosterone compared with placebo in improving
Immunohistological analysis of prostatic inflammation and gene expression of inflammatory markers on the prostate [6 months before surgery]
Evaluation in hypogonadal patients with both BPH and metabolic syndrome of the effectiveness of 6 months of treatment with testosterone compared with placebo in improving
metabolic parameters [6 months before surgery]
Evaluation in hypogonadal patients with both BPH and metabolic syndrome of the effectiveness of 6 months of treatment with testosterone compared with placebo in improving

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male subjects aged ≥ 18 years on the waiting list for simple prostatectomy for BPH
Diagnosis of metabolic syndrome (AHA / NHLBI) defined by the presence of three or more of the following parameters: visceral obesity (waist circumference> or = 102 cm), fasting glucose (> or = 100 mg / dL) or a history of diabetes mellitus or treatment with antidiabetic drugs, high triglycerides (> or = 150 mg / dL) or treatment, high levels of blood pressure (BP> or = 130/85 mm Hg) or drug treatment and reduced levels of HDL cholesterol (<or = 40 mg / dL) or treatment.
Diagnosis of prostatic inflammation defined by a score greater than 15 at the NIH-CPSI questionnaire
Capacity to give consent for study participation, after being adequately informed of the aims, benefits, risks, time and motion of the study

Exclusion Criteria:

Participation in another clinical trial;
Previous diagnosis, presence or suspected malignancy of the prostate or breast cancer;
PSA values10ng/mL
Values of hematocrit ≥ 52%
Use of 5alpha-reductase inhibitor drugs in the previous three months;
Presence of a serious organic disease or mental diagnosed by a specialist psychiatrist (eg major depression medication) suspected on the basis of medical history and / or physical examination of the patient
Presence of conditions that may affect the compliance to the study;
Presence of severe allergy or hypersensitivity to study drug (active ingredient or excipients of the formulation);