Ramipril for the Treatment of Oligospermia

• Sponsor: Weill Medical College of Cornell University
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Oligospermia; Teratospermia; Asthenozoospermia; Male Infertility	Drug: Ramipril; Drug: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ramipril for the Treatment of Oligospermia: A Double-Blind Randomized Control Trial
• Study Start Date: July 2013
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Ramipril; Angiotensin Converting Enzyme Inhibitor; Other Name: Altace
Sham Comparator: 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.	Drug: Placebo; Placebo pill that will match the treatment pill; Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :

1. Sperm Density in Infertile Men With Documented Oligospermia. [ Time Frame: 32 weeks ]

Secondary Outcome Measures :

1. Total Motile Sperm Count(TMSC), Total Sperm Count, Sperm Motility, and Morphology in the Ejaculate. [ Time Frame: 32 weeks ]
   The efficacy of ramipril in improving total sperm count will be evaluated, as well as, improving sperm motility, and morphology.
2. Pregnancy Rate [ Time Frame: 32 weeks ]
3. Hormonal Profile [ Time Frame: 32 weeks ]
   LH, FSH, serum testosterone, prolactin

Other Outcome Measures:

1. Seminal Angiotensin II and Serum Bradykinin Levels [ Time Frame: 32 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, New York

Weill Cornell Medical College, Department of Urology

New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

• Principal Investigator: Peter N Schlegel, MD; Weill Medical College of Cornell University

More Information

Additional Information:

Department of Urology Cornell 

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT01856361 History of Changes
• Other Study ID Numbers: 1301013462
• First Posted: May 17, 2013
• Results First Posted: June 2, 2017
• Last Update Posted: June 2, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Weill Medical College of Cornell University:

Male infertility; Low sperm count; Poor sperm motility; Poor Sperm shape and morphology

Additional relevant MeSH terms:

Infertility; Infertility, Male; Oligospermia; Asthenozoospermia; Teratozoospermia; Genital Diseases, Male; Genital Diseases, Female; Ramipril; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents