Infertility, Male, Sperm DNA Fragmentation
Conditions
Brief summary
Double-blind placebo-controlled randomized trial of daily escitalopram for 6 weeks in healthy men with normal semen analyses and no psychiatric history of depression, bipolar, mania or suicidal ideation. Hormone profiles, semen analysis, sperm DNA fragmentation, and sexual function will be measured at baseline, after 6 weeks of therapy, and 4 weeks after discontinuation of therapy (10 weeks into study).
Detailed description
SSRI medications, specifically escitalopram is a very commonly prescribed medication among men of reproductive age. Significant evidence exists that they may be harmful for paternal fertility potential in both animal and human studies. However, high quality data is lacking, particularly among commonly used SSRI's such as escitalopram. As such, it is important to properly evaluate the potential effect of escitalopram in a randomized placebo controlled fashion. Results will be important in guiding urologists, psychiatrists and family practitioners regarding discussion surrounding SSRI use in their patients interested in fertility.
Interventions
DRUGEscitalopram
10mg by mouth daily for 6 weeks
OTHERPlacebo
matched placebo control by mouth for 6 weeks
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal semen analyses, or semen analyses with at least 5 million sperm * Normal TUNEL value (\<7%) * Willing to engage in at least weekly sexual activity, with a partner or alone for the duration of the 10-week study
Exclusion criteria
* Azoospermia or severe oligospermia (\<5million sperm per semen analysis) * Presently attempting to conceive pregnancy * Sexual dysfunction preventing ability to provide semen analysis throughout study or engage in weekly sexual activity * Current psychiatric disorder including: bipolar, mania, depression, generalized anxiety, social phobia, panic attacks, obsessive compulsive disorder, and schizophrenia. * Family history of bipolar disorder, or suicide (including 2nd degree relatives) * Present use of psychotropic agents (prescription or herbal) or anticonvulsants * Use of sleeping pills * Alcohol consumption greater that 2oz/day * Use of illicit drugs * Inability to read, follow instructions or complete questionnaires in English. * Use of hormonal medications in past 3 months (androgens, androgen blockade, anabolic steroids, estrogens, herbal) * Use of medications to enhance sexual function * History of chemotherapy or pelvic radiation * Use of Monoamine Oxidase inhibitors (MAOi's) or tricyclic antidepressants (TCAs) within 14 days * Liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Have Abnormal (>7%) TUNEL DNA Fragmentation Levels After 6 Weeks of Treatment | 6 weeks | TUNEL assay for sperm DNA fragmentation,Percentage of patients who have abnormal (\>7%) TUNEL DNA fragmentation levels after 6 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Who Have Abnormal DNA Fragmentation Levels at 10 Weeks (4 Weeks Following Cessation of Treatment) | 10 weeks | Tunnel assay of the DNA fragmentation, Percentage of patients who have abnormal DNA fragmentation levels at 10 weeks (4 weeks following cessation of treatment) |
| Absolute Change in DNA Fragmentation Percentage | 0 (baseline), 6, 10 weeks | Absolute change in DNA fragmentation percentage across treatment groups from baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Prolactin (ng/mL) | 0 (baseline), 6, 10 weeks | serum prolactin measurement,Change in serum prolactin (ng/mL) |
| Serum Testosterone Measurement | 0 (baseline), 6, 10 weeks | Change in serum testosterone (ng/dL) |
| Change in International Index of Erectile Function Survey | 0 (Baseline), 6, 10 weeks | International Index of Erectile Function (IIEF) Survey. Severe Erectile Dysfunction (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no Erectile Dysfunction (22-25) |
| Change in Serum Luteinizing Hormone (LH) (mIU/mL) | 0 (baseline), 6, 10 weeks | Serum Luteinizing hormone measurement, Change in serum luteinizing hormone (LH) (mIU/mL) |
| Change in Serum Follicle-stimulating Hormone (FSH) (mIU/mL) | 0 (baseline), 6, 10 weeks | Serum follicle-stimulating hormone measurement,Change in serum follicle-stimulating hormone (FSH) (mIU/mL) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram 10mg by mouth daily for 6 weeks
Escitalopram: 10mg by mouth daily for 6 weeks | 37 |
| Placebo Matched placebo control by mouth for 6 weeks.
Placebo: matched placebo control by mouth for 6 weeks | 38 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Escitalopram | 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 | 37 Participants | 38 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 34 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 16 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 37 Participants | 38 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 0 / 37 | 0 / 38 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 |
Outcome results
Primary
Percentage of Patients Who Have Abnormal (>7%) TUNEL DNA Fragmentation Levels After 6 Weeks of Treatment
TUNEL assay for sperm DNA fragmentation,Percentage of patients who have abnormal (\>7%) TUNEL DNA fragmentation levels after 6 weeks of treatment
Time frame: 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Percentage of Patients Who Have Abnormal (>7%) TUNEL DNA Fragmentation Levels After 6 Weeks of Treatment | 27 Percentage |
| Placebo | Percentage of Patients Who Have Abnormal (>7%) TUNEL DNA Fragmentation Levels After 6 Weeks of Treatment | 21.05 Percentage |
Secondary
Absolute Change in DNA Fragmentation Percentage
Absolute change in DNA fragmentation percentage across treatment groups from baseline
Time frame: 0 (baseline), 6, 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Escitalopram | Absolute Change in DNA Fragmentation Percentage | Baseline | 8.28 Percentage | Standard Deviation 5.61 |
| Escitalopram | Absolute Change in DNA Fragmentation Percentage | 6 Weeks | 9.22 Percentage | Standard Deviation 7.23 |
| Escitalopram | Absolute Change in DNA Fragmentation Percentage | 10 Weeks | 7.93 Percentage | Standard Deviation 7.05 |
| Placebo | Absolute Change in DNA Fragmentation Percentage | Baseline | 7.2 Percentage | Standard Deviation 5.66 |
| Placebo | Absolute Change in DNA Fragmentation Percentage | 6 Weeks | 8.3 Percentage | Standard Deviation 7.29 |
| Placebo | Absolute Change in DNA Fragmentation Percentage | 10 Weeks | 7.39 Percentage | Standard Deviation 4.66 |
Secondary
Percentage of Patients Who Have Abnormal DNA Fragmentation Levels at 10 Weeks (4 Weeks Following Cessation of Treatment)
Tunnel assay of the DNA fragmentation, Percentage of patients who have abnormal DNA fragmentation levels at 10 weeks (4 weeks following cessation of treatment)
Time frame: 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Percentage of Patients Who Have Abnormal DNA Fragmentation Levels at 10 Weeks (4 Weeks Following Cessation of Treatment) | 24 participants |
| Placebo | Percentage of Patients Who Have Abnormal DNA Fragmentation Levels at 10 Weeks (4 Weeks Following Cessation of Treatment) | 18 participants |
Other Pre-specified
Change in International Index of Erectile Function Survey
International Index of Erectile Function (IIEF) Survey. Severe Erectile Dysfunction (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no Erectile Dysfunction (22-25)
Time frame: 0 (Baseline), 6, 10 weeks
Other Pre-specified
Change in Serum Follicle-stimulating Hormone (FSH) (mIU/mL)
Serum follicle-stimulating hormone measurement,Change in serum follicle-stimulating hormone (FSH) (mIU/mL)
Time frame: 0 (baseline), 6, 10 weeks
Other Pre-specified
Change in Serum Luteinizing Hormone (LH) (mIU/mL)
Serum Luteinizing hormone measurement, Change in serum luteinizing hormone (LH) (mIU/mL)
Time frame: 0 (baseline), 6, 10 weeks
Other Pre-specified
Change in Serum Prolactin (ng/mL)
serum prolactin measurement,Change in serum prolactin (ng/mL)
Time frame: 0 (baseline), 6, 10 weeks
Other Pre-specified
Serum Testosterone Measurement
Change in serum testosterone (ng/dL)
Time frame: 0 (baseline), 6, 10 weeks