The Influence of Urate-lowering Therapy on Sperm Quality of Male Gouty Patients：A Prospective Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The mean change from baseline to week 12 in semen quality.
研究概览
简要总结
Gout is a kind of crystal-associated arthropathy caused by monosodium urate deposition, which is directly related to hyperuricemia caused by purine metabolic disorder and/or decreased uric acid excretion. It belongs to the category of metabolic rheumatism. Gout can be complicated with kidney disease. The severe cases can occur joint destruction, renal function damage, and often accompanied by hyperlipidemia, hypertension, diabetes, arteriosclerosis and coronary heart disease and so on.
The prevalence of gout varies greatly from different countries. But on the whole, the prevalence of gout is increasing year by year, and the incidence of gout is getting younger. With the continuous improvement of living standards in today's society, middle-aged men have quietly become a high incidence group of gout.
The pathophysiological basis of gout is hyperuricemia, so reducing uric acid is the core of gout treatment. The reducing uric acid in patients with gout is a long-term process, and the drug can not be stopped after the serum uric acid is reduced to normal. Once patients with gout stop taking uric acid-lowering drugs, serum uric acid quickly returns to the pre-treatment level, which can not only cause gout attack again, but also bring the risk of kidney and cardio-cerebrovascular involvement if serum uric acid does not reach the control standard for a long time. Therefore, uric acid-lowering therapy requires the use of a minimum dose of uric acid-lowering drugs to maintain long-term uric acid levels.
In recent years, with the aggravation of environmental pollution and the postponement of childbearing age, the incidence of male infertility is increasing year by year. However, there are relatively few studies on the effect of gout caused by hyperuricemia on male sperm quality. With the rejuvenation of gout patients and the long-term nature of uric acid-lowering therapy, the safety of uric acid-lowering drugs in male gout patients of childbearing age during pregnancy is not sure. Coupled with the opening of China's comprehensive second-child policy, more and more male gout patients join this fertility group. Unfortunately, so far, no animal or human trial has observed the effect of uric acid-lowering drugs on sperm quality. For this reason, this study intends to carry out this observational clinical trial to evaluate the effect of long-term use of uric acid-lowering drugs on male sperm quality by collecting relevant data of patients with gout treated with uric acid-lowering drugs. Aim to provide a theoretical basis for the safety of uric acid-lowering drugs during pregnancy.
详细描述
- Research drugs. Three kinds of uric acid lowering drugs, allopurinol, febuxostat and benzbromarone, will be evaluated in this study.
- Study design and sample size calculation. This study was designed as a single-center prospective cohort study. After a careful search of the relevant literature, there are no reports of similar studies, so it is impossible to accurately estimate the sample size. Therefore, this study planned to enroll 20 patients with gout who were using allopurinol, febuxostat and benzbromarone to reduce uric acid, respectively. It is planned to recruit 5 gouty patients and 5 control males every month. Therefore, the whole study needs to last at least 12 months after initiation
- Research process. The process of this study does not affect the routine diagnosis and treatment procedures of patients with gout. Our research team is made up of doctors majoring in rheumatology and andrology. Therefore, we can make routine clinical diagnosis and treatment according to the specific conditions of patients with gout.
- Screening period. It will takes about 2 weeks, including the following forms:
- Patients with gout are in acute attack. According to the guidelines for the diagnosis and treatment of gout, we should first give them anti-inflammatory and analgesic treatment. Non-steroidal anti-inflammatory drugs(NSAIDs) or colchicine can be selected to control acute symptoms. Then we performed the semen analysis after the joint swelling and pain is completely improved. If the patient meets our admission criteria, urate-lowering therapy should be initiated according to the clinical practice. And we regard this time as week 0. NSAIDs or colchicine can be prophylacticly used for at least 2 weeks combined with urate-lowering treatment in case of gout flare.
- Patients with gout in remission. For this kind of patients, we directly conduct semen analysis. If the results meets our admission criteria, urate-lowering therapy should be initiated according to the clinical practice. We also regard this time as week 0. And the preventive use of NSAIDs or colchicine is the same as above.
- Follow-up stage. The follow-up cycle was calculated after the beginning of urate-lowering therapy. We will detect the blood routine, urine routine, liver and kidney function and serum uric acid at the time of screening and week 2, week 4, week 8 and week 12 visits. The patients will receive the repeated sperm analysis at week 4 and week 12, respectively. At the same time, we will collect all the corresponding data on the case report form.
4、Patient withdrawal. Patients can drop out of the trial at any time. Researchers can also persuade patients to withdraw for a variety of reasons, including baseline screening for sperm quality below World Health Organization (WHO) standards, adverse events, safety concerns, or patients' failure to comply with the trial regimen.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male, aged 18 ~45 years old;
- •In accordance with the gout classification criteria of the American Rheumatic Society in 1977 or ACR/EULAR (European Alliance against Rheumatism) in 2015 ;
- •Willing to receive uric acid-lowering drugs regularly for at least 3 months;
- •No drugs affecting sperm quality were taken within 3 months before screening.
- •Sign the informed consent form.
排除标准
- •Patients who have a pregnancy plan during the trial;
- •Patients with severe heart, liver, kidney and other important organs, blood and endocrine system diseases, the evaluation criteria are as follows:
- •Heart disease: patients with a history of heart disease such as decompensated cardiac insufficiency, refractory hypertension or coronary heart disease;
- •Liver function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal reference value (ULN);
- •Renal function: complicated with renal tubule and/or renal interstitial lesions, or renal insufficiency: serum creatinine≥ULN or glomerular filtration rate (eGFR) <60ml/min/1.73m2;
- •leukocyte (WBC) count <3 × 109/L and/or hemoglobin (Hb) <100g/L and/or platelet (PLT) count <80 × 109/L;
- •Other serious diseases, such as tumors, etc;
- •Those who are unable to cooperate with the treatment of mental illness or other reasons;
- •Allergic constitution or multi-drug allergy;
- •Those who are known to be allergic or intolerant to uric acid-lowering drugs in the trial;
- •Chromosome abnormality or deletion of AZF region of Y chromosome;
- •Previous history of orchitis, epididymitis, mumps or varicocele affecting sperm quality;
- •Positive semen bacterial culture, or Chlamydia trachomatis, Ureaplasma Urealyticum and Mycoplasma hominis;
- •Those who have a history of exposure to high temperature, chemistry, physics or toxicants in the past year;
- •Those who undergo X-ray or CT examination in the past 3 months and during the period of enrollment;
- •Patients with other systemic diseases who are being treated with other drugs that may affect semen quality.
结局指标
主要结局
The mean change from baseline to week 12 in semen quality.
时间窗: At baseline, week 4 and week 12 visits
According to the current world health orgnization semen analysis guidelines, semen quality evaluation can not use a single index to evaluate semen quality grade. The change of semen quality needs to be evaluated comprehensively from two aspects, namely basic semen analysis and sperm DNA integrity analysis Therefore, all the measurements will be aggregated to arrive at the reported value as semen quality.
次要结局
- Comparison of the reproductive hormone levels, oxidative stress level,the rate of the target serum urate level of <6.0 mg/dl at week12 of treatment, et al among different groups.(At baseline, week 4 and week 12 visits)
研究者
Jinxia Zhao
Deputy department director
Peking University Third Hospital