Clinical trial NCT03669692: Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
Official title: Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Prostatic Hyperplasia, Benign
Metabolic Syndrome
Keywords: Prostate
Caloric Restriction
Metabolic Syndrome
Heart Rate Variability
Lead sponsor: Complexo Hospitalario Universitario de A Coruña
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 0
Sex: MALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open Randomized Clinical Trials
Primary purpose: TREATMENT

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) .


Eligibility criteria: 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.

Primary outcomes:
measure: Change in the International Prostatic Symptoms Score (IPPS)
timeFrame: Change from Baseline IPPS at 36 months
Secondary outcomes:
measure: Change in Prostatic volumen
timeFrame: Change from Baseline Prostatic Volumen at 36 months
measure: Change in Insulin Resistance
timeFrame: Change from Baseline Insulin Resistance at 36 months
measure: Prostatic Specific Antigen (PSA)
timeFrame: Before and after 36 months
measure: Testosterone
timeFrame: Before and after 36 months
measure: IIEF5
timeFrame: Before and after 36 months
measure: Prostate Cancer
timeFrame: 36 months
measure: Change in SF36 score
timeFrame: Change from Baseline SF36 questionnaire at 36 months
measure: Tamsulosin prescription
timeFrame: Before and after 36 months
measure: Dutasteride/Finasteride prescription percentage
timeFrame: Before and after 36 months
measure: Surgery for BPH
timeFrame: Before and after 36 months
measure: Change in Body Mass Index (BMI) variation
timeFrame: Change from Baseline BMI at 36 months
measure: Change in Abdominal perimeter variation
timeFrame: Change from Baseline abdominal perimeter variation at 36 months
measure: Diastolic pressure variation
timeFrame: Before and after 36 months
measure: Sistolic pressure variation
timeFrame: Before and after 36 months
measure: Heart rate variation
timeFrame: Before and after 36 months
measure: Total cholesterol variation
timeFrame: Before and after 36 months
measure: High Density Lipoprotein cholesterol variation
timeFrame: Before and after 36 months
measure: LDL cholesterol variation
timeFrame: Before and after 36 months
measure: Triglyceride variation
timeFrame: Before and after 36 months
measure: Alanine transaminase (ALT) variation
timeFrame: Before and after 36 months
measure: Aspartate transaminase (AST) variation
timeFrame: Before and after 36 months
measure: HRV parameter - Parasympathetic Nervous System Index (PNS index)
timeFrame: Before and after 36 months
measure: HRV parameter - Sympathetic Nervous System Index (SNS index)
timeFrame: Before and after 36 months
measure: HRV parameter - Low frequency / High Frequency Ratio (LF/HF ratio)
timeFrame: Before and after 36 months
Other outcomes:
Locations:
city: A Coruña
country: Spain
facility: Jose Luis Ponce Diaz-Reixa
Study officials:
References: