Ramipril for the Treatment of Oligospermia

Ramipril for the Treatment of Oligospermia: A Double-Blind Randomized Control Trial

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.

Study Overview

• Status: Terminated
• Conditions: Male Infertility; Oligospermia; Asthenozoospermia; Teratospermia
• Intervention / Treatment: Drug: Ramipril; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College, Department of Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sperm Density in Infertile Men With Documented Oligospermia.	32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	32 weeks
Pregnancy Rate		32 weeks
Hormonal Profile	LH, FSH, serum testosterone, prolactin	32 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Seminal Angiotensin II and Serum Bradykinin Levels	32 weeks

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Department of Urology Cornell

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 17, 2013

Study Record Updates

• Last Update Posted (Actual): June 2, 2017
• Last Update Submitted That Met QC Criteria: April 27, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Male infertility; Low sperm count; Poor sperm motility; Poor Sperm shape and morphology
• Additional Relevant MeSH Terms: Infertility; Infertility, Male; Oligospermia; Asthenozoospermia; Teratozoospermia; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Ramipril
• Other Study ID Numbers: 1301013462

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided