Impact of Duloxetine on Male Fertility

Depression Clinical Trial

Official title:

Impact of Duloxetine on Male Fertility

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03038867
• Other study ID #: 1603017099
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2016
• Est. completion date: August 31, 2018

Study information

• Verified date: February 2020
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: August 31, 2018
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Infertility
• Infertility, Male

Intervention

Drug:
• Duloxetine
Duloxetine orally 60mg daily for 5 weeks, then taper to 30mg daily for 1 week
• Placebo
Placebo orally 2 tabs daily for 5 weeks, then taper to 1 tab daily for 1 week

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Abnormal Sperm DNA Fragmentation at 6 Weeks	Number of participants with TUNEL values > 25% at 6 weeks in each treatment group	6 Weeks (primary time point of interest)
Primary	Number of Participants With Abnormal Sperm DNA Fragmentation at 0 Weeks	Number of participants with Tunel Values > 25% at 0 Weeks (baseline) in each treatment group	0 weeks
Primary	Number of Participants With Abnormal Sperm DNA Fragmentation at 2 Weeks	Number of participants with Tunel values > 25% at 2 weeks in each treatment group	2 weeks
Primary	Number of Participants With Abnormal Sperm DNA Fragmentation at 8 Weeks	Number of participants with Tunel values > 25% at 8 weeks in each treatment group	8 weeks
Primary	Number of Participants With Abnormal Sperm DNA Fragmentation at 10 Weeks	Number of participants with Tunel values > 25% at 10 weeks in each treatment group	10 Weeks
Secondary	Sperm Concentration at 0 Weeks	Sperm concentration (number of sperm/mL) in semen analysis at 0 weeks	0 weeks
Secondary	Sperm Concentration at 2 Weeks	Sperm concentration (number of sperm/mL) in semen analysis at 2 weeks	2 weeks
Secondary	Sperm Concentration at 6 Weeks	Sperm concentration (number of sperm/mL) in semen analysis at 6 weeks	6 weeks
Secondary	Sperm Concentration at 8 Weeks	Sperm concentration (number of sperm/mL) in semen analysis at 8 weeks	8 weeks
Secondary	Sperm Concentration at 10 Weeks	Sperm concentration (number of sperm/mL) in semen analysis at 10 weeks	10 Weeks
Secondary	Sperm Motility at 0 Weeks	Sperm motility (mean percent) at 0 weeks	0 weeks
Secondary	Sperm Motility at 2 Weeks	Sperm motility (mean percent) at 2 weeks	2 weeks
Secondary	Sperm Motility at 6 Weeks	Sperm motility (mean percent) at 6 weeks	6 weeks
Secondary	Sperm Motility at 8 Weeks	Sperm motility (mean percent) at 8 weeks	8 weeks
Secondary	Sperm Motility at 10 Weeks	Sperm motility (mean percent) at 10 weeks	10 Weeks
Secondary	Sperm Head Defects at 0 Weeks	Sperm head defects (mean number) at 0 weeks	0 weeks
Secondary	Sperm Head Defects at 2 Weeks	Sperm head defects (mean number) at 2 weeks	2 weeks
Secondary	Sperm Head Defects at 6 Weeks	Sperm head defects (mean number) at 6 weeks	6 weeks
Secondary	Sperm Head Defects at 8 Weeks	Sperm head defects (mean number) at 8 weeks	8 weeks
Secondary	Sperm Head Defects at 10 Weeks	Sperm head defects (mean number) at 10 weeks	10 Weeks
Secondary	Sperm Neck Defects at 0 Weeks	Sperm neck defects (mean number) at 0 weeks	0 weeks
Secondary	Sperm Neck Defects at 2 Weeks	Sperm neck defects (mean number) at 2 weeks	2 weeks
Secondary	Sperm Neck Defects at 6 Weeks	Sperm neck defects (mean number) at 6 weeks	6 weeks
Secondary	Sperm Neck Defects at 8 Weeks	Sperm neck defects (mean number) at 8 weeks	8 weeks
Secondary	Sperm Neck Defects at 10 Weeks	Sperm neck defects (mean number) at 10 weeks	10 Weeks
Secondary	Sperm Tail Defects at 0 Weeks	Sperm tail defects (mean number) at 0 weeks	0 weeks
Secondary	Sperm Tail Defects at 2 Weeks	Sperm tail defects (mean number) at 2 weeks	2 weeks
Secondary	Sperm Tail Defects at 6 Weeks	Sperm tail defects (mean number) at 6 weeks	6 weeks
Secondary	Sperm Tail Defects at 8 Weeks	Sperm tail defects (mean number) at 8 weeks	8 weeks
Secondary	Sperm Tail Defects at 10 Weeks	Sperm tail defects (mean number) at 10 weeks	10 Weeks
Secondary	Testosterone Level at 0 Weeks	Testosterone level (ng/dL) at 0 weeks	0 weeks
Secondary	Testosterone Level at 2 Weeks	Testosterone level (ng/dL) at 2 weeks	2 weeks
Secondary	Testosterone Level at 6 Weeks	Testosterone level (ng/dL) at 6 weeks	6 weeks
Secondary	Testosterone Level at 8 Weeks	Testosterone level (ng/dL) at 8 weeks	8 weeks
Secondary	Testosterone Level at 10 Weeks	Testosterone level (ng/dL) at 10 weeks	10 Weeks
Secondary	Estrogen Level at 0 Weeks	Estrogen level (pg/mL) at 0 weeks	0 weeks
Secondary	Estrogen Level at 2 Weeks	Estrogen level (pg/mL) at 2 weeks	2 weeks
Secondary	Estrogen Level at 6 Weeks	Estrogen level (pg/mL) at 6 weeks	6 weeks
Secondary	Estrogen Level at 8 Weeks	Estrogen level (pg/mL) at 8 weeks	8 weeks
Secondary	Estrogen Level at 10 Weeks	Estrogen level (pg/mL) at 10 weeks	10 Weeks
Secondary	Prolactin Level at 0 Weeks	Prolactin level (ng/mL) at 0 weeks	0 weeks
Secondary	Prolactin Level at 2 Weeks	Prolactin level (ng/mL) at 2 weeks	2 weeks
Secondary	Prolactin Level at 6 Weeks	Prolactin level (ng/mL) at 6 weeks	6 weeks
Secondary	Prolactin Level at 8 Weeks	Prolactin level (ng/mL) at 8 weeks	8 weeks
Secondary	Prolactin Level at 10 Weeks	Prolactin level (ng/mL) at 10 weeks	10 Weeks
Secondary	Luteinizing Hormone Level at 0 Weeks	Luteinizing hormone level (mIU/mL) at 0 weeks	0 weeks
Secondary	Luteinizing Hormone Level at 2 Weeks	Luteinizing hormone level (mIU/mL) at 2 weeks	2 weeks
Secondary	Luteinizing Hormone Level at 6 Weeks	Luteinizing hormone level (mIU/mL) at 6 weeks	6 weeks
Secondary	Luteinizing Hormone Level at 8 Weeks	Luteinizing hormone level (mIU/mL) at 8 weeks	8 weeks
Secondary	Luteinizing Hormone Level at 10 Weeks	Luteinizing hormone level (mIU/mL) at 10 weeks	10 Weeks
Secondary	Follicle Stimulating Hormone Level at 0 Weeks	Follicle stimulating hormone level (mIU/mL) at 0 weeks	0 weeks
Secondary	Follicle Stimulating Hormone Level at 2 Weeks	Follicle stimulating hormone level (mIU/mL) at 2 weeks	2 weeks
Secondary	Follicle Stimulating Hormone Level at 6 Weeks	Follicle stimulating hormone level (mIU/mL) at 6 weeks	6 weeks
Secondary	Follicle Stimulating Hormone Level at 8 Weeks	Follicle stimulating hormone level (mIU/mL) at 8 weeks	8 weeks
Secondary	Follicle Stimulating Hormone Level at 10 Weeks	Follicle stimulating hormone level (mIU/mL) at 10 weeks	10 Weeks