Open Randomized Clinical Trial to Evaluate the Effects of Intermittent Caloric Restriction in Patients With Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- Change in the International Prostatic Symptoms Score (IPPS)
研究概览
简要总结
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) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Change in the International Prostatic Symptoms Score (IPPS)
时间窗: 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.
次要结局
- Triglyceride variation(Before and after 36 months)
- Testosterone(Before and after 36 months)
- IIEF5(Before and after 36 months)
- Dutasteride/Finasteride prescription percentage(Before and after 36 months)
- Change in Body Mass Index (BMI) variation(Change from Baseline BMI at 36 months)
- Change in Insulin Resistance(Change from Baseline Insulin Resistance at 36 months)
- Change in SF36 score(Change from Baseline SF36 questionnaire at 36 months)
- Change in Abdominal perimeter variation(Change from Baseline abdominal perimeter variation at 36 months)
- Prostate Cancer(36 months)
- Surgery for BPH(Before and after 36 months)
- Sistolic pressure variation(Before and after 36 months)
- Heart rate variation(Before and after 36 months)
- Tamsulosin prescription(Before and after 36 months)
- Alanine transaminase (ALT) variation(Before and after 36 months)
- HRV parameter - Sympathetic Nervous System Index (SNS index)(Before and after 36 months)
- HRV parameter - Low frequency / High Frequency Ratio (LF/HF ratio)(Before and after 36 months)
- Change in Prostatic volumen(Change from Baseline Prostatic Volumen at 36 months)
- Prostatic Specific Antigen (PSA)(Before and after 36 months)
- Total cholesterol variation(Before and after 36 months)
- LDL cholesterol variation(Before and after 36 months)
- Diastolic pressure variation(Before and after 36 months)
- High Density Lipoprotein cholesterol variation(Before and after 36 months)
- Aspartate transaminase (AST) variation(Before and after 36 months)
- HRV parameter - Parasympathetic Nervous System Index (PNS index)(Before and after 36 months)
研究者
José Luis Ponce Díaz-Reixa
Urologist
Complexo Hospitalario Universitario de A Coruña