Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
- Conditions
- Prostatic Hyperplasia, BenignMetabolic Syndrome
- Interventions
- Behavioral: ControlBehavioral: Caloric Restriction
- Registration Number
- NCT03669692
- Lead Sponsor
- Complexo Hospitalario Universitario de A Coruña
- Brief Summary
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) .
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Male
- Target Recruitment
- Not specified
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Control Patients in the control group will be assigned to a free diet (ad libitum), according to the Spanish Association of Urology lifestyle recommendations for patients with LUTS Caloric Restriction Caloric Restriction Patients in the experimental group will be assigned to intermittent caloric restriction, based on an early time restricted eating, with a 16/8 fasting/feeding scheme. The patients in this group will have a RC progressive scheme until achieve a maximum of 5 days a week of fasting.
- Primary Outcome Measures
Name Time Method Change in the International Prostatic Symptoms Score (IPPS) Change from Baseline IPPS at 36 months 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.
- Secondary Outcome Measures
Name Time Method Triglyceride variation Before and after 36 months To evaluate variations on triglyceride, measured as mg/dL.
Testosterone Before and after 36 months To evaluate Testosterone variation
IIEF5 Before and after 36 months To evaluate the International Index of Erectile Function variation
Dutasteride/Finasteride prescription percentage Before and after 36 months 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.
Change in Body Mass Index (BMI) variation Change from Baseline BMI at 36 months To evaluate variations on body mass index, measured as weight (kilograms) divided by height (cm) square.
Change in Insulin Resistance Change from Baseline Insulin Resistance at 36 months To evaluate variations on insuline resistance through the HOMA-IR formula.
Change in SF36 score Change from Baseline SF36 questionnaire at 36 months To evaluate quality of life through SF36 questionnaire.
Change in Abdominal perimeter variation Change from Baseline abdominal perimeter variation at 36 months To evaluate variations on abdominal perimeter, measured as centimeters.
Prostate Cancer 36 months To evaluate prostate cancer incidence
Surgery for BPH Before and after 36 months 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.
Sistolic pressure variation Before and after 36 months To evaluate variations on sistolic pressure variation, measured as mmHg.
Heart rate variation Before and after 36 months To evaluate variations on heart rate, measured as beats per minute.
Tamsulosin prescription Before and after 36 months To assess the incidence of the prescription of Tamsulosin for symptoms relief. It will be analyzed as a percentage of patients with Tamsulosin prescription.
Alanine transaminase (ALT) variation Before and after 36 months To evaluate variations on alanine transaminase, measured as IU.
HRV parameter - Sympathetic Nervous System Index (SNS index) Before and after 36 months 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.
HRV parameter - Low frequency / High Frequency Ratio (LF/HF ratio) Before and after 36 months 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.
Change in Prostatic volumen Change from Baseline Prostatic Volumen at 36 months To evaluate prostatic volumen reduction, trough transrectal sonography
Prostatic Specific Antigen (PSA) Before and after 36 months To evaluate PSA variation
Total cholesterol variation Before and after 36 months To evaluate variations on total cholesterol, measured as mg/dL.
LDL cholesterol variation Before and after 36 months To evaluate variations on LDL cholesterol, measured as mg/dL.
Diastolic pressure variation Before and after 36 months To evaluate variations on diastolic pressure variation, measured as mmHg.
High Density Lipoprotein cholesterol variation Before and after 36 months To evaluate variations on HDL cholesterol, measured as mg/dL.
Aspartate transaminase (AST) variation Before and after 36 months To evaluate variations on aspartate transaminase, measured as IU.
HRV parameter - Parasympathetic Nervous System Index (PNS index) Before and after 36 months 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
Trial Locations
- Locations (1)
Jose Luis Ponce Diaz-Reixa
🇪🇸A Coruña, Spain