Ramipril for the Treatment of Oligospermia

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01856361
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.1

Study Details

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	N/A

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
• 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: Jul 1, 2013
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 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 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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. 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.

2. Pregnancy Rate [32 weeks]

3. Hormonal Profile [32 weeks]

   LH, FSH, serum testosterone, prolactin

Other Outcome Measures

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Department of Urology Cornell

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT01856361
• Other Study ID Numbers: 1301013462
• First Posted: May 17, 2013
• Last Update Posted: Jun 2, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• 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; Ramipril

Study Results

Participant Flow

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	1	1
COMPLETED	1	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ramipril	Placebo	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	1	1	2
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Measure Participants	0	0

2. Secondary Outcome

Title	Total Motile Sperm Count(TMSC), Total Sperm Count, Sperm Motility, and Morphology in the Ejaculate.
Description	The efficacy of ramipril in improving total sperm count will be evaluated, as well as, improving sperm motility, and morphology.
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Measure Participants	0	0

3. Secondary Outcome

Title	Pregnancy Rate
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Measure Participants	0	0

4. Secondary Outcome

Title	Hormonal Profile
Description	LH, FSH, serum testosterone, prolactin
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Measure Participants	0	0

5. Other Pre-specified Outcome

Title	Seminal Angiotensin II and Serum Bradykinin Levels
Time Frame	32 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ramipril	Placebo
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Arm/Group Title	Ramipril		Placebo
Arm/Group Description	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		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
All Cause Mortality
	Ramipril		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ramipril		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Ramipril		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.