Clinical trial NCT03038867: Impact of Duloxetine on Male Fertility
Official title: Impact of Duloxetine on Male Fertility
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infertility, Male
Depression
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2017-02-01
Enrollment: 69
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Blinded, placebo-controlled, randomized controlled trial
Primary purpose: OTHER

Brief summary: The investigators are conducting a placebo-controlled, randomized control trial with duloxetine in healthy, fertile men not previously on any antidepressants. Participants will be randomized to either the duloxetine or placebo groups for 6 weeks. The investigators will assess changes in sperm DNA fragmentation at 0, 2, 6, 8, and 10 weeks. Other outcomes measured will include semen parameters (sperm concentration, motility, morphology), hormone levels (testosterone, estrogen, prolactin, LH, FSH), and sexual function (IIEF and MSHQ) surveys.

Detailed description: Antidepressant medications are commonly prescribed in the USA not only for depression, but also for anxiety disorders such as generalized anxiety disorder and obsessive-compulsive disorder, premature ejaculation, post-traumatic stress disorder, and neuropathic pain. Despite being widely prescribed in the United States in men of reproductive age, the impact of antidepressants on fertility has not been extensively studied.

After noticing worsened semen parameters in men on anti-depressants, the investigators performed the first prospective study to demonstrate a deleterious impact of selective serotonin reuptake inhibitors (SSRI) on sperm DNA integrity, which has been linked to reproductive outcomes. Further small studies have corroborated the negative impact of SSRIs on male fertility, as assessed by semen parameters and/or sperm DNA integrity.

No studies have examined the impact of a newer, but similar, class of antidepressant - the serotonin-norepinephrine reuptake inhibitor (SNRI). Like SSRIs, SNRIs inhibit the reuptake of serotonin, but also act on norepinephrine. The use of SNRIs has increased recently due to their slightly improved efficacy profile when compared to SSRIs. Duloxetine is an SNRI and is one of the most commonly prescribed anti-depressants in the United States.

The investigators are conducting this trial to determine whether or not the administration of duloxetine will result in a deterioration in sperm DNA fragmentation in healthy, fertile men.

Eligibility criteria: Inclusion Criteria:

* Healthy men aged 18-65 years old;
* normal or borderline semen analysis (sperm concentration \> 10 million/mL, sperm motility \> 30%, sperm morphology \> 3%);
* willing to engage in sexual activity (alone or with a partner) at least once per week for the duration of the study;
* capable of providing semen sample.

Exclusion Criteria:

* Clinically detected varicocele;
* oligoasthenoteratospermia or azoospermia on semen analysis;
* ongoing attempts to initiate pregnancy;
* current sexual dysfunction (classified as moderate or worse on IIEF);
* history of seizure disorder;
* history of previous chemotherapy or radiation therapy;
* current psychiatric history or history of bipolar disorder;
* family history of bipolar disorder, depression, or suicide;
* use of any psychotropic medications or anticonvulsants;
* use of sleeping pills more than once per week;
* use of any hormonal medications on a daily or intermittent basis during the preceding 3 months;
* use of medications which may affect hormone measures and/or sexual function;
* inability to read, follow instructions, or complete questionnaires in English;
* consumption of tobacco or illicit drugs;
* consumption of \>2oz of alcohol daily.

Primary outcomes:
measure: Number of Participants With Abnormal Sperm DNA Fragmentation at 6 Weeks
timeFrame: 6 Weeks (primary time point of interest)
measure: Number of Participants With Abnormal Sperm DNA Fragmentation at 0 Weeks
timeFrame: 0 weeks
measure: Number of Participants With Abnormal Sperm DNA Fragmentation at 2 Weeks
timeFrame: 2 weeks
measure: Number of Participants With Abnormal Sperm DNA Fragmentation at 8 Weeks
timeFrame: 8 weeks
measure: Number of Participants With Abnormal Sperm DNA Fragmentation at 10 Weeks
timeFrame: 10 Weeks
Secondary outcomes:
measure: Sperm Concentration at 0 Weeks
timeFrame: 0 weeks
measure: Sperm Concentration at 2 Weeks
timeFrame: 2 weeks
measure: Sperm Concentration at 6 Weeks
timeFrame: 6 weeks
measure: Sperm Concentration at 8 Weeks
timeFrame: 8 weeks
measure: Sperm Concentration at 10 Weeks
timeFrame: 10 Weeks
measure: Sperm Motility at 0 Weeks
timeFrame: 0 weeks
measure: Sperm Motility at 2 Weeks
timeFrame: 2 weeks
measure: Sperm Motility at 6 Weeks
timeFrame: 6 weeks
measure: Sperm Motility at 8 Weeks
timeFrame: 8 weeks
measure: Sperm Motility at 10 Weeks
timeFrame: 10 Weeks
measure: Sperm Head Defects at 0 Weeks
timeFrame: 0 weeks
measure: Sperm Head Defects at 2 Weeks
timeFrame: 2 weeks
measure: Sperm Head Defects at 6 Weeks
timeFrame: 6 weeks
measure: Sperm Head Defects at 8 Weeks
timeFrame: 8 weeks
measure: Sperm Head Defects at 10 Weeks
timeFrame: 10 Weeks
measure: Sperm Neck Defects at 0 Weeks
timeFrame: 0 weeks
measure: Sperm Neck Defects at 2 Weeks
timeFrame: 2 weeks
measure: Sperm Neck Defects at 6 Weeks
timeFrame: 6 weeks
measure: Sperm Neck Defects at 8 Weeks
timeFrame: 8 weeks
measure: Sperm Neck Defects at 10 Weeks
timeFrame: 10 Weeks
measure: Sperm Tail Defects at 0 Weeks
timeFrame: 0 weeks
measure: Sperm Tail Defects at 2 Weeks
timeFrame: 2 weeks
measure: Sperm Tail Defects at 6 Weeks
timeFrame: 6 weeks
measure: Sperm Tail Defects at 8 Weeks
timeFrame: 8 weeks
measure: Sperm Tail Defects at 10 Weeks
timeFrame: 10 Weeks
measure: Testosterone Level at 0 Weeks
timeFrame: 0 weeks
measure: Testosterone Level at 2 Weeks
timeFrame: 2 weeks
measure: Testosterone Level at 6 Weeks
timeFrame: 6 weeks
measure: Testosterone Level at 8 Weeks
timeFrame: 8 weeks
measure: Testosterone Level at 10 Weeks
timeFrame: 10 Weeks
measure: Estrogen Level at 0 Weeks
timeFrame: 0 weeks
measure: Estrogen Level at 2 Weeks
timeFrame: 2 weeks
measure: Estrogen Level at 6 Weeks
timeFrame: 6 weeks
measure: Estrogen Level at 8 Weeks
timeFrame: 8 weeks
measure: Estrogen Level at 10 Weeks
timeFrame: 10 Weeks
measure: Prolactin Level at 0 Weeks
timeFrame: 0 weeks
measure: Prolactin Level at 2 Weeks
timeFrame: 2 weeks
measure: Prolactin Level at 6 Weeks
timeFrame: 6 weeks
measure: Prolactin Level at 8 Weeks
timeFrame: 8 weeks
measure: Prolactin Level at 10 Weeks
timeFrame: 10 Weeks
measure: Luteinizing Hormone Level at 0 Weeks
timeFrame: 0 weeks
measure: Luteinizing Hormone Level at 2 Weeks
timeFrame: 2 weeks
measure: Luteinizing Hormone Level at 6 Weeks
timeFrame: 6 weeks
measure: Luteinizing Hormone Level at 8 Weeks
timeFrame: 8 weeks
measure: Luteinizing Hormone Level at 10 Weeks
timeFrame: 10 Weeks
measure: Follicle Stimulating Hormone Level at 0 Weeks
timeFrame: 0 weeks
measure: Follicle Stimulating Hormone Level at 2 Weeks
timeFrame: 2 weeks
measure: Follicle Stimulating Hormone Level at 6 Weeks
timeFrame: 6 weeks
measure: Follicle Stimulating Hormone Level at 8 Weeks
timeFrame: 8 weeks
measure: Follicle Stimulating Hormone Level at 10 Weeks
timeFrame: 10 Weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Peter Schlegel, MD
role: STUDY_CHAIR
affiliation: Weill Medical College of Cornell University
name: Nahid Punjani, MD
role: PRINCIPAL_INVESTIGATOR
References: