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

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ClinicalTrials.gov Identifier: NCT03669692
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
José Luis Ponce Díaz-Reixa, Complexo Hospitalario Universitario de A Coruña

Tracking Information
First Submitted Date  ICMJE September 9, 2018
First Posted Date  ICMJE September 13, 2018
Last Update Posted Date September 21, 2018
Actual Study Start Date  ICMJE July 10, 2018
Estimated Primary Completion Date December 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
Change in the International Prostatic Symptoms Score (IPPS) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
International Prostatic Symptoms Score (IPPS) variation [ Time Frame: 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.
Change History Complete list of historical versions of study NCT03669692 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Change in Prostatic volumen [ Time Frame: Change from Baseline Prostatic Volumen at 36 months ]
    To evaluate prostatic volumen reduction, trough transrectal sonography
  • Change in Insulin Resistance [ Time Frame: Change from Baseline Insulin Resistance at 36 months ]
    To evaluate variations on insuline resistance through the HOMA-IR formula.
  • Prostatic Specific Antigen (PSA) [ Time Frame: Before and after 36 months ]
    To evaluate PSA variation
  • Testosterone [ Time Frame: Before and after 36 months ]
    To evaluate Testosterone variation
  • IIEF5 [ Time Frame: Before and after 36 months ]
    To evaluate the International Index of Erectile Function variation
  • Prostate Cancer [ Time Frame: 36 months ]
    To evaluate prostate cancer incidence
  • Change in SF36 score [ Time Frame: Change from Baseline SF36 questionnaire at 36 months ]
    To evaluate quality of life through SF36 questionnaire.
  • Tamsulosin prescription [ Time Frame: 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.
  • Dutasteride/Finasteride prescription percentage [ Time Frame: 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.
  • Surgery for BPH [ Time Frame: 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.
  • Change in Body Mass Index (BMI) variation [ Time Frame: 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 Abdominal perimeter variation [ Time Frame: Change from Baseline abdominal perimeter variation at 36 months ]
    To evaluate variations on abdominal perimeter, measured as centimeters.
  • Diastolic pressure variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on diastolic pressure variation, measured as mmHg.
  • Sistolic pressure variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on sistolic pressure variation, measured as mmHg.
  • Heart rate variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on heart rate, measured as beats per minute.
  • Total cholesterol variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on total cholesterol, measured as mg/dL.
  • High Density Lipoprotein cholesterol variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on HDL cholesterol, measured as mg/dL.
  • LDL cholesterol variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on LDL cholesterol, measured as mg/dL.
  • Triglyceride variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on triglyceride, measured as mg/dL.
  • Alanine transaminase (ALT) variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on alanine transaminase, measured as IU.
  • Aspartate transaminase (AST) variation [ Time Frame: Before and after 36 months ]
    To evaluate variations on aspartate transaminase, measured as IU.
  • HRV parameter - Parasympathetic Nervous System Index (PNS index) [ Time Frame: 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
  • HRV parameter - Sympathetic Nervous System Index (SNS index) [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2018)
  • Prostatic volumen [ Time Frame: 36 months ]
    To evaluate prostatic volumen reduction, trough transrectal sonography
  • Insulin Resistance [ Time Frame: 36 months ]
    To evaluate variations on insuline resistance through the HOMA-IR formula.
  • Prostatic Specific Antigen (PSA) [ Time Frame: 36 months ]
    To evaluate PSA variation
  • Testosterone [ Time Frame: 36 months ]
    To evaluate Testosterone variation
  • IIEF5 [ Time Frame: 36 months ]
    To evaluate the International Index of Erectile Function variation
  • Prostate Cancer [ Time Frame: 36 months ]
    To evaluate prostate cancer incidence
  • SF36 [ Time Frame: 36 months ]
    To evaluate quality of life through SF36 questionnaire.
  • Tamsulosin prescription [ Time Frame: 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.
  • Dutasteride/Finasteride prescription percentage [ Time Frame: 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.
  • Surgery for BPH [ Time Frame: 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.
  • Body Mass Index (BMI) variation [ Time Frame: 36 months ]
    To evaluate variations on body mass index, measured as weight (kilograms) divided by height (cm) square.
  • Abdominal perimeter variation [ Time Frame: 36 months ]
    To evaluate variations on abdominal perimeter, measured as centimeters.
  • Diastolic pressure variation [ Time Frame: 36 months ]
    To evaluate variations on diastolic pressure variation, measured as mmHg.
  • Sistolic pressure variation [ Time Frame: 36 months ]
    To evaluate variations on sistolic pressure variation, measured as mmHg.
  • Heart rate variation [ Time Frame: 36 months ]
    To evaluate variations on heart rate, measured as beats per minute.
  • Total cholesterol variation [ Time Frame: 36 moths ]
    To evaluate variations on total cholesterol, measured as mg/dL.
  • High Density Lipoprotein cholesterol variation [ Time Frame: 36 moths ]
    To evaluate variations on HDL cholesterol, measured as mg/dL.
  • LDL cholesterol variation [ Time Frame: 36 moths ]
    To evaluate variations on LDL cholesterol, measured as mg/dL.
  • Triglyceride variation [ Time Frame: 36 moths ]
    To evaluate variations on triglyceride, measured as mg/dL.
  • Alanine transaminase (ALT) variation [ Time Frame: 36 moths ]
    To evaluate variations on alanine transaminase, measured as IU.
  • Aspartate transaminase (AST) variation [ Time Frame: 36 moths ]
    To evaluate variations on aspartate transaminase, measured as IU.
  • HRV measures [ Time Frame: 36 months ]
    To evaluate variations on heart rate variability parameters.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open Randomized Clinical Trials
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostatic Hyperplasia, Benign
  • Metabolic Syndrome
Intervention  ICMJE
  • Behavioral: 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.
  • 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.
Study Arms  ICMJE
  • Active Comparator: 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
    Intervention: Behavioral: Control
  • Experimental: 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.

    Intervention: Behavioral: Caloric Restriction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 12, 2018)
92
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date December 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03669692
Other Study ID Numbers  ICMJE URO - CHUAC - 002 - HBP - RC
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party José Luis Ponce Díaz-Reixa, Complexo Hospitalario Universitario de A Coruña
Study Sponsor  ICMJE Complexo Hospitalario Universitario de A Coruña
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Complexo Hospitalario Universitario de A Coruña
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP