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

NCT03669692 | Withdrawn

• 1 other identifier: URO - CHUAC - 002 - HBP - RC
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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) .

Conditions

Prostatic Hyperplasia, Benign; Metabolic Syndrome

Keywords

Prostate; Caloric Restriction; Metabolic Syndrome; Heart Rate Variability

Outcome Measures

Primary Outcomes (1)

• 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.

  Change from Baseline IPPS at 36 months

Secondary Outcomes (24)

• Change in Prostatic volumen

  Change from Baseline Prostatic Volumen at 36 months

• Change in Insulin Resistance

  Change from Baseline Insulin Resistance at 36 months

• Prostatic Specific Antigen (PSA)

  Before and after 36 months

• Testosterone

  Before and after 36 months

• IIEF5

  Before and after 36 months

Study Arms (2)

Control

ACTIVE COMPARATOR

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

Behavioral: Control

Caloric Restriction

EXPERIMENTAL

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.

Behavioral: Caloric Restriction

Interventions

Caloric Restriction BEHAVIORAL

Subjects will be trained to perform intermittent caloric restriction, based on an early time restricted feeding, with a 16/8 hour fasting / feeding schedule, respectively.

Caloric Restriction

Control BEHAVIORAL

Subjects will receive diet and lifestyle recommendations from the Spanish Association of Urology, for symptoms secondary to HBP, without restriction in the meal schedule.

Control

Eligibility Criteria

• Age: 45 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Complexo Hospitalario Universitario de A Coruña: lead

Study Sites (1)

Jose Luis Ponce Diaz-Reixa

A Coruña, 15006, Spain

Location

MeSH Terms

Conditions

Prostatic Hyperplasia; Metabolic Syndrome

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Urologist

Model Details: Open Randomized Clinical Trials

Study Record Dates

• First Submitted: September 9, 2018
• First Posted: September 13, 2018
• Study Start: July 10, 2018
• Primary Completion: December 10, 2022
• Study Completion: January 1, 2023
• Last Updated: August 2, 2021

Record last verified: 2021-07

Locations

ES (1)