Probenecid for Male Infertility Due to Spinal Cord Injury
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Male
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: University of Miami
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This is a study of infertility which often occurs in men with spinal cord injury. Most men with spinal cord injury have a normal sperm count but abnormally low sperm motility - which means that the sperm does not swim well. This study will determine if a medicine given by mouth will improve sperm motility in men with spinal cord injuries. The medicine is called probenecid.
Do I need to stop my current medications to join the trial?
Yes, you will need to stop taking methotrexate, aspirin, other salicylates, or anti-inflammatory medicines to participate in the trial.
Is Probenecid safe for human use?
Probenecid has been used safely in humans for other conditions, but specific safety data for its use in treating male infertility due to spinal cord injury is not available. Generally, it is important to consult with a healthcare provider to understand potential risks and benefits.
12345How does the drug Probenecid differ from other treatments for male infertility due to spinal cord injury?
Probenecid is unique because it is primarily used to treat gout by increasing uric acid excretion, and its use for male infertility due to spinal cord injury is novel, as traditional treatments focus on managing erectile and ejaculatory dysfunctions or improving semen quality through methods like vibratory stimulation or electroejaculation.
678910Eligibility Criteria
This trial is for men over 18 with traumatic spinal cord injury who have been injured for at least a year. It's not for those with zero sperm count, indwelling catheters, unstable conditions like Crohn's or colon cancer, implanted electrical devices, allergies to probenecid, history of kidney stones/ulcers, recent UTI fever, or taking certain medications.Participant Groups
The study tests if probenecid can improve the swimming ability of sperm in men with spinal cord injuries. Participants will receive either a placebo (no active ingredient) or probenecid at doses of 250 mg or 500 mg to see which works better.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Half dose groupExperimental Treatment1 Intervention
Participants in this group will receive half the dose of probenecid for a total of 90 days.
Group II: Full dose groupExperimental Treatment1 Intervention
Participants in this group will receive the full dose of probenecid for a total of 90 days.
Group III: Control-placebo groupPlacebo Group1 Intervention
Participants in this group will receive a placebo dose (No active ingredient) for a total of 90 days.
Probenecid is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Benemid for:
- Gout
- Hyperuricemia
🇨🇦 Approved in Canada as Probecid for:
- Gout
- Hyperuricemia
🇪🇺 Approved in European Union as Probenecid for:
- Gout
- Hyperuricemia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of MiamiMiami, FL
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Who is running the clinical trial?
University of MiamiLead Sponsor
United States Department of DefenseCollaborator
References
Histopathology of the male reproductive system induced by the fungicide benomyl. [2018]Benomyl is an effective fungicide that has been in use for many years. This chemical and its primary metabolite, carbendazim, are microtubule poisons that are relatively nontoxic to all mammalian organs, except for the male reproductive system. Its primary effects, at moderate to low dosages, are on the testis, where it causes sloughing of germ cells in a stage-dependent manner. Sloughing is caused by the effects of the chemical on microtubules and intermediate filaments of the Sertoli cell. These effects spread to dividing germ cells and also lead to abnormal development of the head of elongating spermatids. At higher dosages, it causes occlusion of the efferent ducts, blocking passage of sperm from the rete testis to epididymis. The mechanism of occlusion appears to be related to fluid reabsorption, sperm stasis, followed by leukocyte chemotaxis, sperm granulomas, fibrosis and often the formation of abnormal microcanals. The occlusion results in a rapid swelling of the testis and ultimately seminiferous tubular atrophy and infertility. In conclusion, studies that reveal long term testicular atrophy following chronic or subchronic exposure to a toxicant should be re-examined for histopathological lesions in the efferent ductules and head of the epididymis. Lesions in the male track that cause blockage may induce permanent testicular damage and a decrease in sperm production.
Cardiovascular/Pulmonary Medications and Male Reproduction. [2018]Cardiovascular and respiratory medications are used by men of reproductive age although use of the former is most prevalent in advanced age. Many of these drugs have been associated with sexual dysfunction, including erectile and ejaculatory dysfunction, but for most there is insufficient evidence to link their use with testicular dysfunction, reduced semen quality or infertility. Some exceptions are the irreversible α1-adrenergic antagonist phenoxybenzamine, which carries a high risk of retrograde ejaculation; the specific α1A-adrenergic antagonists silodosin and tamsulosin, used primarily to treat BPH/lower urinary tract symptoms, which can cause retrograde ejaculation; and the peripheral β1-adrenergic antagonist atenolol, used to treat hypertension, which may decrease testosterone/free-testosterone levels. In this chapter, we review the evidence available regarding adverse reactions on male reproduction of adrenergic receptor agonists/antagonists, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, digoxin, and hydralazine. For some of these medications, there is some evidence for male reproductive effects, along with some solid work in experimental and companion animal species suggesting negative effects. In contrast, and of special note, are calcium channel blockers, which have long been included on lists of medications with the potential to cause male infertility. This turns out to be a good example of a substance with profound effects on sperm function in vitro, but with limited evidence for in vivo effects on semen quality or fertility, even in experimental species. We hope that the evidence provided in this chapter will stimulate additional studies for these important classes of medications.
Adverse drug reactions on male fertility. [2023]For several years, fertility disorders have been on the increase worldwide. These disorders affect both sexes, but are more pronounced in men; and in half of cases the etiology is unknown. The role of drugs in male infertility has been little studied to date. Most of the available data comes from experimental animal studies, with all their limitations. With the exception of a few drugs, such as certain anticancer agents, human data are rare. This article describes the mainly drugs known to have deleterious effects on male fertility, the mechanisms leading to these effects and methods used to assess the risk of drug-induced male infertility. It underlines the need for further work in experimental research, clinical trials and post-marketing surveillance to improve our knowledge of drugs that induce male infertility. Although these adverse effects are not life-threatening, they can have a significant impact on patients' lives.
Case reports of individuals with oligospermia and methylene chloride exposures. [2019]Between December 7, 1984 and June, 1986, 34 men with exposure to methylene chloride were evaluated at the Greater Cincinnati Occupational Health Center (GCOHC). Their primary complaint involved problems associated with central nervous system dysfunction. However, 8 of the 34 men complained of testicular, epididymal or lower abdominal pain (found on exam to be prostatic in origin) and had clinical histories consistent with infertility. Semen specimens from four volunteers were found to be in the subfertile or infertile range with regard to motility, morphology and sperm density.
Reproductive toxicity of methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) in male Wistar rats. [2019]Methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) is a systemic fungicide which has been implicated in producing damage to the testes. The present investigation was undertaken to evaluate the functional and behavioral significance of this reported benomyl-induced damage to male rats using a 70-day feeding study followed by a 70-day recovery study. Adult male Wistar rats were fed laboratory chow containing 1.0, 6.3, or 203 ppm benomyl, with control animals receiving standard laboratory chow. Ejaculate sperm counts were significantly depressed (P less than or equal to 0.05) in male ingesting 203 ppm benomyl during the 70 day feeding phase. A significant decrease in relative testicular weights and a lowered male fertility index were observed in all benomyl-treatment groups. No significant alterations in plasma testosterone, LH, or FSH levels were observed during the feeding phase. Benomyl ingestion did not alter male copulatory behavior, nor was benomyl found to be an inducer of dominant lethal mutations. Identical studies performed during the recovery phase demonstrated that the benomyl-induced alterations in testicular function were reversible. The male fertility index, ejaculate sperm content, and testicular weights returned to control values during this phase.
Infertility in men with spinal cord injury. [2005]Infertility is a significant and frustrating problem for many men after spinal cord injury. The two major causes are poor semen quality and ejaculatory dysfunction. Factors attributed to poor semen quality include stasis of prostatic fluid, testicular hyperthermia, recurrent urinary tract infections, abnormal testicular histology, possible changes in the hypothalamic-pituitary-testicular axis, possible sperm antibodies, chronic long-term use of various medications, and type of bladder management. Further work is needed to define the impact and importance of each of these factors. Ejaculations are reported to occur in only 5% of men with spinal cord injury (SCI) who have complete upper motor lesions and 18% of those who have complete lower motor lesions. Ejaculations occur in up to 70% of men with incomplete lesions. Methods that have been used to induce an ejaculate include intrathecal neostigmine, subcutaneous physostigmine, direct aspiration of sperm from the vas deferens, vibratory stimulation, electroejaculation, and direct stimulation of the hypogastric nerve. The most commonly used methods in the United States are electroejaculation and vibratory stimulation; using these two methods, ejaculates can be obtained up to 85% and 59% of the time, respectively. Each of these methods has advantages and disadvantages. Particular care needs to be given to monitoring men undergoing these procedures who are prone to autonomic dysreflexia. The future outlook is encouraging once improved technology for obtaining semen and various methods to assist reproduction, such as in vitro fertilization, are available.
Male fertility following spinal cord injury: an update. [2016]Spinal cord injury (SCI) occurs most often in young men at the peak of their reproductive health. The majority of men with SCI cannot father children naturally. Three major complications contribute to infertility in men with SCI: erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. Erectile dysfunction can be managed by regimens available to the general population, including oral administration of phosphodiesterase-5 (PDE-5) inhibitors, intracavernosal injections, vacuum devices, and penile prostheses. Semen may be obtained from anejaculatory men with SCI via the medically assisted ejaculation methods of penile vibratory stimulation (PVS) or electroejaculation (EEJ). Sperm retrieval is also possible via prostate massage or surgical sperm retrieval. Most men with SCI have abnormal semen quality characterized by normal sperm concentrations but abnormally low sperm motility and viability. Accessory gland dysfunction has been proposed as the cause of these abnormalities. Leukocytospermia is evident in most SCI patients. Additionally, elevated concentrations of pro-inflammatory cytokines and elevated concentrations of inflammasome components are found in their semen. Neutralization of these constituents has resulted in improved sperm motility. There is a recent and alarming trend in the management of infertility in couples with SCI male partners. Although many men with SCI have sufficient motile sperm in their ejaculates for attempting intrauterine insemination (IUI) or even intravaginal insemination, surgical sperm retrieval is often introduced as the first and only sperm retrieval method for these couples. Surgical sperm retrieval commits the couple to the most advanced, expensive, and invasive method of assisted conception: in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI). Couples should be informed of all options, including semen retrieval by PVS or EEJ. Intravaginal insemination or IUI should be considered when indicated.
A comprehensive approach to the management of male infertility following spinal cord injury. [2019]To review the outcomes of management of male infertility following spinal cord injury in a specialised fertility clinic.
Management of sexual disorders in spinal cord injured patients. [2018]Spinal cord injured (SCI) patients have sexual disorders including erectile dysfunction (ED), impotence, priapism, ejaculatory dysfunction and infertility. Treatments for erectile dysfunction include four steps. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors (PDE5I) such as Sildenafil (Viagra), intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (SNM). Priapism can be resolved spontaneously if there is no ischemia found on blood gas measurement or by Phenylephrine. For anejaculatory dysfunction, massage, vibrator, electrical stimulation and direct surgical biopsy can be used to obtain sperm which can then be used for intra-uterine or in-vitro fertilization. Infertility treatment in male SCI patients involves a combination of the above treatments for erectile and anejaculatory dysfunctions. The basic approach to and management of sexual dysfunction in female SCI patients are similar as for men but do not require treatment for erectile or ejaculatory problems.
Treatment of infertility in men with spinal cord injury. [2021]Most men with spinal cord injury (SCI) are infertile. Erectile dysfunction, ejaculatory dysfunction and semen abnormalities contribute to the problem. Treatments for erectile dysfunction include phosphodiesterase type 5 inhibitors, intracavernous injections of alprostadil, penile prostheses, and vacuum constriction devices. In anejaculatory patients who wish to father children, semen retrieval is necessary. Penile vibratory stimulation is recommended as the first line of treatment. Patients who fail penile vibratory stimulation can be referred for electroejaculation. If this approach is not possible, prostate massage is an alternative. Surgical sperm retrieval should be considered as a last resort when other methods fail. Most men with SCI have a unique semen profile characterized by normal sperm count but abnormally low sperm motility. Scientific investigations indicate that accessory gland dysfunction and abnormal semen constituents contribute to the problem. Despite abnormalities, sperm from men with SCI can successfully induce pregnancy. In selected couples, the simple method of intravaginal insemination is a viable option. Another option is intrauterine insemination. The efficacy of intrauterine insemination increases as the total motile sperm count inseminated increases. In vitro fertilization and intracytoplasmic sperm injection are options in cases of extremely low total motile sperm count. Reproductive outcomes for SCI male factor infertility are similar to outcomes for general male factor infertility.