Asthenozoospermia, Male Infertility, Oligospermia, Teratospermia
Conditions
Keywords
Male infertility, Low sperm count, Poor sperm motility, Poor Sperm shape and morphology
Brief summary
This is a randomized controlled trial to evaluate the effect of ramipril in stimulating and promoting sperm production in men with low sperm count. Ramipril is an Angiotensin Converting Enzyme Inhibitor (ACEI) currently used to treat high blood pressure. However, previous studies have shown that this class of medications can improve sperm parameters. The purpose of this study is to evaluate the efficacy of ramipril compared to placebo (Substance That is not known to have treatment effect), in improving sperm density in infertile men with documented low sperm count. This study will help us identify subjects that might benefit from treatment with this medication, and the effect it will have on sperm count, shape, and motility.
Detailed description
Approximately half of all infertility problems are caused by male factors. These men account for 17% of patients at the primary health care level that seek help for infertility. Oligospermia (Low sperm count) of unknown cause occurs in up to 60% of men with unexplained infertility. Certain group of patients with oligospermia can father children, but those with infertility have long posed a major therapeutic challenge. A variety of empirical non-specific treatments have been used, in attempt to improve their semen characteristics and fertility. In the past, androgens were suggested as a treatment; however, exogenous testosterone was found to exert negative feedback on the pituitary-gonadal axis and thereby suppresses Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) secretion then adversely affects sperm production. Other treatment modalities like clomiphene citrate, tamoxifen, recombinant FSH, zinc, selenium, and L-carnitine have been tried with minimal success. In the present study we are proposing the use of an angiotensin converting enzyme inhibitor (ACEI) for the treatment of oligospermia. A recently published pilot study showed that the use of lisinopril improved sperm quantity and quality in oligospermic men. ACEI are inexpensive, safe, widely available, and, if effective in improving sperm production and quality, could avert couples from undergoing invasive procedures.
Interventions
DRUGRamipril
Angiotensin Converting Enzyme Inhibitor
DRUGPlacebo
Placebo pill that will match the treatment pill
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male partner of a couple presenting for infertility. 2. Moderate abnormalities of semen parameters (Mean sperm density \<20 million, but ≥ 3 million/ml), and/or motility \< 50%, and/or \< 4% abnormal morphology on at least two separate occasions. 3. Age 18-45 years. 4. Normal renal function defined as Glomerular filtration rate \> 90
Exclusion criteria
1. Patients that are currently taking thiazide, cyclosporin, lithium, and allopurinol or the use of these medications in the last 2 weeks. 2. The frequent use of NSAIDS (3 or more times a week). 3. Vasectomy reversal. 4. Regular use of tobacco products. 5. Mean white blood cell count \>1 million/ml in the ejaculate. 6. Inability or unwillingness to participate in evaluations required by the study. 7. Potassium \> 5.0. 8. Systolic blood pressure \< 90 mmHg. 9. Currently use of ACEI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sperm Density in Infertile Men With Documented Oligospermia. | 32 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Motile Sperm Count(TMSC), Total Sperm Count, Sperm Motility, and Morphology in the Ejaculate. | 32 weeks | The efficacy of ramipril in improving total sperm count will be evaluated, as well as, improving sperm motility, and morphology. |
| Pregnancy Rate | 32 weeks | — |
| Hormonal Profile | 32 weeks | LH, FSH, serum testosterone, prolactin |
Other
| Measure | Time frame |
|---|---|
| Seminal Angiotensin II and Serum Bradykinin Levels | 32 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ramipril The initial dose of ramipril will be 2.5 mg that will be started at visit 2, week zero of the study. The dose will be increased to 5 mg during visit 3, 4 weeks into the study, for a total of 32 weeks.
Ramipril: Angiotensin Converting Enzyme Inhibitor | 1 |
| Placebo The placebo group will get a similar pill that will be started at visit 2, week zero of the study. Subjects will be asked to double the dose by taking two pills during visit 3, four weeks into the study, for a total of 32 weeks.
Placebo: Placebo pill that will match the treatment pill | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Ramipril | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Sperm Density in Infertile Men With Documented Oligospermia.
Time frame: 32 weeks
Population: Data was not collected on the 2 participants as the principal investigator on this trial moved to a different practice and thus the study terminated before any results could be analyzed.
Secondary
Hormonal Profile
LH, FSH, serum testosterone, prolactin
Time frame: 32 weeks
Population: Data was not collected on the 2 participants as the principal investigator on this trial moved to a different practice and thus the study terminated before any results could be analyzed.
Secondary
Pregnancy Rate
Time frame: 32 weeks
Population: Data was not collected on the 2 participants as the principal investigator on this trial moved to a different practice and thus the study terminated before any results could be analyzed.
Secondary
Total Motile Sperm Count(TMSC), Total Sperm Count, Sperm Motility, and Morphology in the Ejaculate.
The efficacy of ramipril in improving total sperm count will be evaluated, as well as, improving sperm motility, and morphology.
Time frame: 32 weeks
Population: Data was not collected on the 2 participants as the principal investigator on this trial moved to a different practice and thus the study terminated before any results could be analyzed.
Other Pre-specified
Seminal Angiotensin II and Serum Bradykinin Levels
Time frame: 32 weeks
Population: Data was not collected on the 2 participants as the principal investigator on this trial moved to a different practice and thus the study terminated before any results could be analyzed.