Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.
Primary Purpose
Azoospermia, Nonobstructive, Oligozoospermia
Status
Completed
Phase
Phase 3
Locations
Singapore
Study Type
Interventional
Intervention
Letrozole
Sponsored by
About this trial
This is an interventional treatment trial for Azoospermia, Nonobstructive
Eligibility Criteria
Inclusion Criteria
- Patients with non-obstructive azoospermia (absence of sperm in the pellets of two centrifuged semen samples collected 30-60 days apart)
- Patients with non-obstructive azoospermia who do not yield spermatozoa with fine needle aspiration (FNA)
- Patients with severe oligozoospermia (presence of sperm concentration less than 5 million per ml in both semen samples collected 30-60 days apart)
- Normal sperm appearance, consistency, liquefaction, volume and pH
- Patient must not possess any chromosomal aberrations
Exclusion Criteria
- Possible etiology of infertility present
- Seminal white blood cell concentration more than 10 million per ml
- Positive seminal culture analysis
- Positive urethral swab for chlamydia test
- Smoker
- Drug or alcohol abuse
- Ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs, previous cancer radiotherapy or chemotherapy)
- Palpable varicocele
- X-ray exposure in the previous 8 months
- Y chromosome microdeletion
- Karyotype abnormalities (Klinefelter syndrome)
Sites / Locations
- KK Women's and Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Letrozole
Arm Description
Participants will be assigned to receive Letrozole 2.5 mg once a day for 4 months
Outcomes
Primary Outcome Measures
Sperm density
Sperm motility
Secondary Outcome Measures
Total serum Testosterone level
Total serum Estradiol level
Total serum Follicle Stimulating Hormone level
Total serum Luteinizing Hormone level
Full Information
NCT ID
NCT02900105
First Posted
August 30, 2016
Last Updated
August 15, 2017
Sponsor
KK Women's and Children's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02900105
Brief Title
Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.
Official Title
Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
KK Women's and Children's Hospital
4. Oversight
5. Study Description
Brief Summary
The investigators hope to learn if Letrozole is effective and safe in improving severe male infertility by increasing testosterone, decreasing oestradiol and stimulating sperm production thereby improving sperm motility (movement) and concentration. The study is being conducted because Letrozole is not yet proven to be a standard treatment in subjects with absent or very low sperm counts. The investigators are hoping to determine whether Letrozole is equal or superior to no treatment.
Detailed Description
This is a pilot study with recruitment carried out in a single centre where participants will be assigned to receive Letrozole 2.5 mg once a day for 4 months. The following data will be collected: semen analyses, clinical history including smoking status, BMI, Y microdeletion, karyotype and FSH, LH, testosterone, E2, drug side effects and effects on libido. The following assessments will be performed before and 4 months after drug administration: sperm analyses, FSH, LH, E2 and testosterone measurements.
Prior to recruitment, the study participant would have undergone the routine investigations for evaluating azoospermia or severe oligozoospermia. These would include FSH, LH, testosterone, karyotyping, Y chromosome microdeletion genetic studies and at least 1 seminal analysis. Despite the availability of biochemical techniques to differentiate non-obstructive azoospermia (NOA) patients from obstructive azoospermia patients, fine needle aspiration (FNA) has been regarded as a highly informative and a minimally invasive method often routinely done in the investigation of azoospermia. All patients with NOA would have a FNA performed as part of their routine workup which would be done before recruitment and initiation of Letrozole. The safety of FNA use is also regarded as being supportive for the researchers against any possible patient lawsuits resulting from any impaired spermatogenesis induced by an off-label prescription. All oligozoospermic patients will be offered to have their sperm cryopreserved before drug administration. The investigations must have been performed within a 6 month time frame prior to recruitment.
There will be 3 clinic visits during the dosing period and 1 post dosing follow up visit. During the initial visit where recruitment into the study occurs, the participant will be prescribed the medication. One week later, a telephone interview will be conducted to review for side effects and arrange an early appointment at patient request. One month later, the participant will be reviewed in clinic and a side effect check list will be conducted. Telephone interviews will be conducted again at 2nd and 3rd month from administration of the drug. At 4th month from administration of the drug, the blood tests and semen analysis will be performed. It is likely that the participant will still be followed up for enrolment into IVF / ICSI programme should spontaneous pregnancy fail to occur. The window period for all clinic visits and telephone interviews is +/- 5 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Azoospermia, Nonobstructive, Oligozoospermia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Letrozole
Arm Type
Experimental
Arm Description
Participants will be assigned to receive Letrozole 2.5 mg once a day for 4 months
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
Letrozole 2.5mg (1 tablet) once a day for 4 months
Primary Outcome Measure Information:
Title
Sperm density
Time Frame
After 4 months dosage of Letrozole
Title
Sperm motility
Time Frame
After 4 months dosage of Letrozole
Secondary Outcome Measure Information:
Title
Total serum Testosterone level
Time Frame
After 4 months dosage of Letrozole
Title
Total serum Estradiol level
Time Frame
After 4 months dosage of Letrozole
Title
Total serum Follicle Stimulating Hormone level
Time Frame
After 4 months dosage of Letrozole
Title
Total serum Luteinizing Hormone level
Time Frame
After 4 months dosage of Letrozole
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria
Patients with non-obstructive azoospermia (absence of sperm in the pellets of two centrifuged semen samples collected 30-60 days apart)
Patients with non-obstructive azoospermia who do not yield spermatozoa with fine needle aspiration (FNA)
Patients with severe oligozoospermia (presence of sperm concentration less than 5 million per ml in both semen samples collected 30-60 days apart)
Normal sperm appearance, consistency, liquefaction, volume and pH
Patient must not possess any chromosomal aberrations
Exclusion Criteria
Possible etiology of infertility present
Seminal white blood cell concentration more than 10 million per ml
Positive seminal culture analysis
Positive urethral swab for chlamydia test
Smoker
Drug or alcohol abuse
Ongoing medical treatment (gonadotropins, anabolic steroids, cancer chemotherapy, non-steroidal anti-inflammatory drugs, previous cancer radiotherapy or chemotherapy)
Palpable varicocele
X-ray exposure in the previous 8 months
Y chromosome microdeletion
Karyotype abnormalities (Klinefelter syndrome)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shuling Liu
Organizational Affiliation
KK Women's and Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
KK Women's and Children's Hospital
City
Singapore
ZIP/Postal Code
229899
Country
Singapore
12. IPD Sharing Statement
Learn more about this trial
Effect of Letrozole on Seminal Parameters in Men With Non Obstructive Azoospermia and Severe Oligozoospermia.
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