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

NCT ID: NCT03669692

Last Updated: 2021-08-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-10
• Study Completion Date: 2023-01-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Caloric Restriction

Intervention Type: 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.

Interventions

Caloric Restriction

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.

Intervention Type: BEHAVIORAL

Control

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

Intervention Type: BEHAVIORAL

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Complexo Hospitalario Universitario de A Coruña

OTHER

Sponsor Role: lead

Responsible Party

José Luis Ponce Díaz-Reixa

Urologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Jose Luis Ponce Diaz-Reixa

A Coruña, , Spain

Countries

Spain

Other Identifiers

URO - CHUAC - 002 - HBP - RC

Identifier Type: -

Identifier Source: org_study_id