Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

Complexo Hospitalario Universitario de A Coruña

Overview

Lower urinary tract symptoms (LUTS) include filling, emptying or post-voiding state alterations; producing symptomatology depending of the underline mechanism. Benign prostatic hyperplasia (BPH) is the most common underlying disease, which increases with age and significantly affects men over 50 years. There are currently no prevention or curative treatment guidelines, as their pathophysiological mechanism is not exactly known. Several factors have been implicated, such as hormones, aging, lifestyle or diet. BPH is associated with metabolic disorders, the basis of which is insulin resistance and its associated pathologies: diabetes, hypertension, obesity, dyslipidemia and metabolic syndrome. Patients without these metabolic signs have a lower incidence of BPH and / or LUTS. Insulin resistance (IR) is associated with greater proliferation and a reduction of cellular apoptosis at the prostate level; leading to an increase in prostate volume or symptoms. Likewise, the autonomic nervous system (ANS) imbalance, both in favor of sympathetic (emptying symptoms) or parasympathetic (filling symptoms), influences LUTS. SNA activity can be measured non-invasively, repetitively and effectively by measuring the heart rate variability (HRV). Caloric restriction with optimal nutrition (CRON, hereinafter only CR) is the most physiologically adapted nutritional alternative to our ancestral needs and has been shown in humans to reduce insulin resistance and associated pathologies. It has also been observed that CR improves the balance of the SNA and allows to improve LUTS. Proliferation inhibition and prostatic apoptosis induction, mediated through CR, by insulin-IGF-1 axis reduction and mTOR metabolic pathways inhibition, are the central axis of this project. CR will be used to reduce insulin resistance, IGF expression and inhibition of the PI3K / AKT / mTOR pathway, to reduce prostate cell proliferation and promote prostatic tissue apoptosis; in this way it will be possible to reduce its volume and improve the symptomatology. Additionally, CR will allow us to evaluate the potential benefits it has on certain metabolic diseases (diabetes, dyslipidemia, obesity, hypertension, etc.), anthropometric values (BMI, abdominal perimeter and skin folds) and autonomic nervous system functionality (HRV) .

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Eligibility

Sex: MALEMin age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signature of specific informed consent for this study. * Metabolic syndrome according to WHO criteria * Current intake food pattern \> 14 hours of duration. * Total PSA below 2,5 ng/mL or total PSA 4 - 10 ng/mL and free/total PSA \> 25% * IPSS score \> 9 points * Maximal flow rate \< 15 cc/secs * Prostatic volume \> 40 cc. Exclusion Criteria: * Active oncological disease; includes patients already treated without complete remission or in current active treatment. * PSA 4 - 10 ng/mL and free/total PSA \< 25% or PSA \> 10 ng/mL * Previous prostatic biopsy in the last 5 years. * Treatment with prostatic phytotherapy in the last 4 weeks. * BPH alphablocking treatment in the last 6 weeks. * 5-alpha-reductase treatment in the last 6 months. * Anticholinergic or betamimetics treatment in the last 4 weeks * Eating, weight management disorder or previous bariatric surgery. * Concurrent treatment with the following drugs in the fasting period: AAS and NSAIDs (except paracetamol). * Concurrent treatment with any of the following steroids: prednisolone, budesonide, dexamethasone, fluidcortisone, hydrocortisone or prednisone. * Major mental illness, which does not allow informed consent. * Previous cardiovascular event in the last 12 months. * Liver, gastrointestinal, renal or severe previous endocrine or decompensated disease in the last 12 months. * Presence of significant vesical lithiasis. * Type I diabetic patients * Type II diabetic patients in treatment with sulfonylureas and sodium-glucose cotransport inhibitors, as well as in patients with insulin therapy. * Loss of patient follow-up * Non-compliance with protocol procedures.

Outcomes

Primary Outcomes

Change in the International Prostatic Symptoms Score (IPPS)

IPSS is a 7 items questionnaire (0-35 points) with 5 answers each, which analyzes the lower urinary tract symptoms. Higher scores indicate greater symptomatology. It is classified as mild up to 7 points, moderate 8-19 and severe greater than 20 points.

Time frame: Change from Baseline IPPS at 36 months

Secondary Outcomes

Change in Prostatic volumen

To evaluate prostatic volumen reduction, trough transrectal sonography

Time frame: Change from Baseline Prostatic Volumen at 36 months

Change in Insulin Resistance

To evaluate variations on insuline resistance through the HOMA-IR formula.

Time frame: Change from Baseline Insulin Resistance at 36 months

Prostatic Specific Antigen (PSA)

To evaluate PSA variation

Time frame: Before and after 36 months

Testosterone

To evaluate Testosterone variation

Time frame: Before and after 36 months

IIEF5

To evaluate the International Index of Erectile Function variation

Time frame: Before and after 36 months

Prostate Cancer

To evaluate prostate cancer incidence

Time frame: 36 months

Change in SF36 score

To evaluate quality of life through SF36 questionnaire.

Time frame: Change from Baseline SF36 questionnaire at 36 months

Tamsulosin prescription

To assess the incidence of the prescription of Tamsulosin for symptoms relief. It will be analyzed as a percentage of patients with Tamsulosin prescription.

Time frame: Before and after 36 months

Dutasteride/Finasteride prescription percentage

To assess the incidence of the prescription of Dutasteride or Finasteride for symptoms relief . It will be analyzed as a percentage of patients with Dutasteride or Finasteride prescription.

Time frame: Before and after 36 months

Surgery for BPH

To assess the surgical treatment needs for BPH. It will be analyzed as a percentage of patients who are operated on by TURP or simple prostatectomy.

Time frame: Before and after 36 months

Change in Body Mass Index (BMI) variation

To evaluate variations on body mass index, measured as weight (kilograms) divided by height (cm) square.

Time frame: Change from Baseline BMI at 36 months

Change in Abdominal perimeter variation

To evaluate variations on abdominal perimeter, measured as centimeters.

Time frame: Change from Baseline abdominal perimeter variation at 36 months

Diastolic pressure variation

To evaluate variations on diastolic pressure variation, measured as mmHg.

Time frame: Before and after 36 months

Sistolic pressure variation

To evaluate variations on sistolic pressure variation, measured as mmHg.

Time frame: Before and after 36 months

Heart rate variation

To evaluate variations on heart rate, measured as beats per minute.

Time frame: Before and after 36 months

Total cholesterol variation

To evaluate variations on total cholesterol, measured as mg/dL.

Time frame: Before and after 36 months

High Density Lipoprotein cholesterol variation

To evaluate variations on HDL cholesterol, measured as mg/dL.

Time frame: Before and after 36 months

LDL cholesterol variation

To evaluate variations on LDL cholesterol, measured as mg/dL.

Time frame: Before and after 36 months

Triglyceride variation

To evaluate variations on triglyceride, measured as mg/dL.

Time frame: Before and after 36 months

Alanine transaminase (ALT) variation

To evaluate variations on alanine transaminase, measured as IU.

Time frame: Before and after 36 months

Aspartate transaminase (AST) variation

To evaluate variations on aspartate transaminase, measured as IU.

Time frame: Before and after 36 months

HRV parameter - Parasympathetic Nervous System Index (PNS index)

To evaluate variations on PNS index, measured by heart rate variability, through Kubios software version 3.1. PNS index includes the following measures: Mean RR, RMSSD and high frequency (HF) power

Time frame: Before and after 36 months

HRV parameter - Sympathetic Nervous System Index (SNS index)

To evaluate variations on SNS index, measured by heart rate variability, through Kubios software version 3.1. The SNS index includes the following measures: Mean HR, Stress index and low frequency (LF) power.

Time frame: Before and after 36 months

HRV parameter - Low frequency / High Frequency Ratio (LF/HF ratio)

To evaluate variations on LF/HF ratio, measured by heart rate variability, through Kubios software version 3.1. Values upper 1.6 indicates SNS predominance.

Time frame: Before and after 36 months

Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes