Clinical Trial: The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A 5-year Prospective, Placebo-controlled, Crossover Evaluation of the Efficacy and Tolerability of Low-dose Lisinopril in Normotensives With Idiopathic Oligospermic Infertility

Brief Summary: This study was conceived in order to explain what the investigators previously observed suggesting that lisinopril, a drug normally used to treat patients with high blood pressure and heart failure, may be effective in treating infertile men with low sperm count. The investigators hypothesized, therefore, that the drug will not only improve sperm quantity and quality but also increase the fertility in such patients. The investigators first of all reviewed the results of previously published investigations and found out that there was only a few previous studies done in humans.with this class of drugs. Besides, the methods used in conducting most of those studies have been so faulted that the results cannot be trusted to be showing the true picture. The investigators looked at the various faults pointed out with respect to the their design and conduct and took care of them while designing the investigators own study. This was an attempt to provide more credible answers to the question of whether lisinopril, and possibly other drugs of similar mode of action, can be useful in rectifying the problem of infertility caused by low sperm count and , if so, whether it will be safe to use it in people who do not have high blood pressure or heart failure. In order to achieve this the investigators studied 33 patients with sperm of low cell concentration, low percentage of motile cells and high percentage of abnormal cells from no known cause. The patients were randomly allocated to receive either lisinopril 2.5mg daily (17 patients) or daily placebo (16 patients)and their sperm characteristics were examined at intervals, starting from the beginning of the study until when it ended 282 weeks later. The patients were also monitored for adverse events throughout the period. The data form all the patients that took part in the random allocation of treatments at the beginning of the study were included in the analysis that followed, irrespective of whether they completed the study

Detailed Summary:

Introduction. Infertility constitutes the cause for about 16.6% of patients seeking consultations at the primary healthcare level. Male factor infertility accounts for about 50% of all infertility problems. Of this percentage seminal fluid abnormality of unknown cause is common, occurring in up to 60% of males with unexplained, this type of infertility. Although some subjects with seminal fluid defects have fathered children those with infertility have long posed a major therapeutic challenge. The rationale for using the various hormonal and non-hormonal drugs currently available is, at best, empirical as most of the efficacy trials conducted yielded conflicting results. Although assisted fertilization techniques have now increased the number of therapeutic options available to couples with infertility problems there is still a very serious limitation in the access to the new technology, especially in low-income countries. Besides, there are additional concerns regarding the possible untoward effects. These lingering problems underscore the need for continuing to search for other effective treatment options that will not only be cheaper and more accessible but also less complicated and non-invasive.

The current study was occasioned by our previous, independent observations (albeit fortuitous) of normalization of seminal fluid parameters as well as spouse pregnancies in two men with long-standing, idiopathic azoospermia. The common factor between the two men was treatment with low-dose (2.5mg per day) Lisinopril, an angiotensin converting enzyme inhibitor or ACEI prescribed for the concomitant hypertension. A review of the available literature on the efficacy studies of various types of angiotensin converting enzyme inhibitors on sperm count and quality revealed a near-consistent finding of improvement in animal studies. However, methodological flaws have rendered the resu
Sponsor: University Of Nigeria Teaching Hospital

Current Primary Outcome:

  • Changes From Baseline in the Seminal Fluid Characteristics Throughout the Study [ Time Frame: Week 96. ]
    The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.
  • Total Sperm Cell Count Per Milliliter of Seminal Fluid. [ Time Frame: Week 96 ]
    the number of sperm cells counted per milliliter volume of seminal fluid
  • Proportion of Sperm Cells With Normal Motility (%) [ Time Frame: Week 96 ]
    This was determined as the proportion (percent) of the total sperm cells exhibiting both rhythmic and propulsive movements considered to be of normal intensity.
  • Proportion of Sperm Cells With Abnormal Morphology (%) [ Time Frame: Week 96 ]
    Proportion (per cent) of sperm cells with abnormal appearance
  • Ejaculate Volume [ Time Frame: Week 282 ]
    The volume in milliliters of seminal fluid produced per ejaculation.
  • Total Sperm Cell Count [ Time Frame: Week 282 ]
    The total number of sperm cells found in each milliliter of seminal fluid.<

    Original Primary Outcome: Changes From Baseline in the Seminal Fluid Characteristics Throughout the Study [ Time Frame: At weeks 0, 6, 12, 24, 48, 96, 102, 114, 138, 186, 282. ]

    The seminal fluid characteristics were assessed twice before the entry of each patient and both at least two-weeks apart. The two values were averaged and recorded as baseline for week 0 while subsequent changes from the baseline were monitored during each of the scheduled visits at weeks 6, 12, 24, 48, 96, 102, 114, 138, 186 and 282. The two groups swopped treatments at the 96th week. The number of pregnancies achieved was also documented throughout the study period.


    Current Secondary Outcome: Adverse Events Monitoring [ Time Frame: At weeks 6, 12, 24, 48, 96, 102, 114,138, 186 and 282 ]

    The patients were encouraged to report every event promptly by phone to one of the authors (NOG), no matter however minor.Blood pressure measurements were done with mercury sphygmomanometers fitted with adult-size cuffs (Accoson, England). Serum potassium levels were estimated using the flame photometric method as described by Davidson and Henry


    Original Secondary Outcome: Same as current

    Information By: University Of Nigeria Teaching Hospital

    Dates:
    Date Received: August 2, 2011
    Date Started: March 1998
    Date Completion:
    Last Updated: September 21, 2013
    Last Verified: September 2013