Male InfertilityPhase 2MOXINCT02421887

Males, Antioxidants, and Infertility Trial

A Phase 2 study testing Antioxidant Supplement in people with Male Infertility, run by Yale University at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Male Infertility
What is being tested?: Antioxidant Supplement
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 171 participants
Where: 10 sitesUnited States
Study dates: Dec 2015to Dec 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

12 or more months of infertility (primary or secondary)
Heterosexual
Cohabitating and able to have regular intercourse
Male:
≥ 18 years of age
At least one abnormal semen parameter on a semen analysis within the past 6 months:

Show all 16Show fewer

Sperm concentration ≤15 Million/ml
Total motility ≤40%
Normal morphology (Kruger) ≤4%
DNA fragmentation (SCSA, DNA fragmentation index) >25%
Female:
≥18 years of age and ≤40 years of age
For women ≥ 35 years of age, evidence of normal ovarian reserve as assessed by menstrual cycle day 3 (+/-2 days) FSH ≤10 IU/L with estradiol ≤ 70 pg/mL, AMH ≥ 1.0 ng/mL, OR antral follicle count >10 within one year prior to study initiation.
Evidence of at least one patent fallopian tube as determined by an hysterosalpingogram or laparoscopy showing at least one patent fallopian tube or a saline infusion sonogram showing spillage of contrast material
Regular cycles defined as ≥25 days and ≤35 days in duration
Evidence of ovulation including biphasic basal body temperatures, positive ovulation predictor kits, or progesterone level ≥3 ng/ml.

Who cannot join

Couple:
Previous sterilization procedures (vasectomy, tubal ligation). The prior procedure may affect study outcomes.
Planning in vitro fertilization in the next 6 months
Male:
Sperm concentration < 5 million/mL on screening semen analysis
Current use of a medication or drug that would affect reproductive function or metabolism (see Appendix C for list)

Show all 19Show fewer

Current multivitamin or herb use (requires 1 month wash-out)
Current serious medical illnesses, such as cancer, heart disease, or cirrhosis
Current use of anticoagulants
Untreated hypothyroidism
Uncontrolled diabetes mellitus
Female:
History of surgically or medically confirmed moderate or severe endometriosis
Body mass index >35 kg/m2
Currently pregnant
History of polycystic ovarian syndrome
Current serious medical illnesses, such as cancer, heart disease, or cirrhosis
History of systemic chemotherapy or pelvic radiation
Current use of a medication or drug that would affect reproductive function or metabolism

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

United States10 sites

Augusta University
Augusta, Georgia, 30912
University of North Carolina
Chapel Hill, North Carolina, 27599
Carolinas Medical Center - Women's Institute
Charlotte, North Carolina, 28204
Pennsylvania State University
Hershey, Pennsylvania, 17033
Keck School of Medicine of University of Southern California
Los Angeles, California, 90089
University of Oklahoma
Oklahoma City, Oklahoma, 73104
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California San Francisco
San Francisco, California, 94115
Wayne State University
Southfield, Michigan, 48034
Stanford University
Sunnyvale, California, 94087

Other trials in United States

About this study

Official title: Males, Antioxidants, and Infertility (MOXI) Trial

The objective of the Males, Antioxidants, and Infertility (MOXI) Trial is to examine whether treatment of infertile males with an antioxidant formulation improves male fertility. The central hypothesis is that treatment of infertile males with antioxidants will improve sperm structure and function, resulting in higher fertilization rates and improved embryo development, leading to higher pregnancy and live birth rates. Findings from this research will be significant in that they will likely lead to an effective, non-hormonal treatment modality for male infertility. An effective treatment for men would also reduce the treatment burden on the female partner, lower costs, and provide effective alternatives to couples with religious or ethical contraindications to ART (Assisted Reproductive Technology). If antioxidants do not improve pregnancy rates, but do improve sperm motility and DNA integrity, they could allow for couples with male factor infertility to use less intensive therapies such as intrauterine insemination. Male fertility specialists currently prescribe antioxidants based on the limited data supporting their use. A negative finding, lack of any benefit, would also alter current treatment of infertile males.

Conditions: Male Infertility
Being tested: Antioxidant Supplement, Placebo
Medical subject headings: Infertility, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Antioxidant SupplementDrug
An antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine
PlaceboOther
Placebo

Study groups in NCT02421887
Study group	Role	What they receive
Antioxidant Supplement	Active comparator	Tablet: Vitamin C, 500 mg; Vitamin D3, 1000 IU; Vitamin E, 400 IU; Folic Acid 1000 mcg; Zinc, 20 mg; Selenium 200 mcg; Lycopene, 10 mg; Capsule: Vitamin D3, 1000 IU, L-Carnitine, 1000 mg Receives: Drug: Antioxidant Supplement
Placebo	Placebo comparator	Not described Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Live Birth Rate
Measured: up to 15 months

Secondary outcomes (9)

Pregnancy Rate
Measured: up to 7 months
Miscarriage Rate
miscarriages per total number of pregnancies
Measured: up to 9 months
Time to Pregnancy
Time to pregnancy will be the chronologic time from randomization to pregnancy detection in days, in which the pregnancy is defined as a human Chorionic Gonadotropin (hCG) value over 5 on 2 separate occasions.
Measured: up to 7 months
Change in Total Motile Sperm Count
Samples will be assessed using a standard semen analysis
Measured: baseline and 3 months
Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)
DFI is the ratio of damaged sperm to total sperm. It is measured using Sperm Chromatin Structure Analysis (SCSA) which was performed on 5000 sperm per sample.
Measured: Baseline and 3 months
Change in Semen Total Motility
Samples assessed using a standard semen analysis
Measured: baseline and 3 months
Change in Sperm Concentration
Samples assessed using a standard semen analysis
Measured: baseline and 3 months
Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria
Samples assessed using a standard semen analysis
Measured: baseline and 3 months
Change in Total Sperm Count
Samples assessed using a standard semen analysis
Measured: baseline and 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2015Dec 2018

First posted21 Apr 2015 (estimated)
Study startDec 2015
Primary completion11 Jun 2018
Study completionDec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Male InfertilityStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 171 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02421887
Sponsor's protocol ID: MOXI
Acronym: MOXI
Status last verified: Aug 2019
First submitted: 19 Mar 2015
Last updated: 4 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.

Publications

Spitzer TL, Trussell JC, Coward RM, Hansen KR, Barnhart KT, Cedars MI, Diamond MP, Krawetz SA, Sun F, Zhang H, Santoro N, Steiner AZ. Biomarkers of Stress and Male Fertility. Reprod Sci. 2022 Apr;29(4):1262-1270. doi: 10.1007/s43032-022-00853-x. Epub 2022 Feb 1.
PubMed 35106743
Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, Krawetz SA, Usadi R, Baker VL, Coward RM, Huang H, Wild R, Masson P, Smith JF, Santoro N, Eisenberg E, Zhang H; Reproductive Medicine Network. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertil Steril. 2020 Mar;113(3):552-560.e3. doi: 10.1016/j.fertnstert.2019.11.008. Epub 2020 Feb 25.
PubMed 32111479

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 3
Comparative Study of Post-Varicocelectomy Myo-inositol vs. Antioxidants vs. Surgery Alone in Infertile Men
Myo-inositol, Post Varicocelectomy
Active, not recruitingPhase 1/2
A Novel Aromatase Inhibitor, Leflutrozole, for Treatment of Non-Obstructive Azoospermia
Infertility Due to Azoospermia, Infertility, Male
Active, not recruiting
YO® Smartphone Home Sperm Test Versus Manual Semen Analysis in Egyptian Men
Semen Analysis, Male Infertility
Not yet recruitingPhase 4
Comparative Efficacy of Antioxidants Alone Versus Combined Therapy With SERMs or FSH in Normogonadotropic Idiopathic OAT Patients: A Randomized Controlled Trial
Oligoasthenoteratozoospermia, Male Infertility
Recruiting
Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
Infertility, Male

All Male Infertility trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Males, Antioxidants, and Infertility (MOXI) Trial
ClinicalTrials.gov ID: NCT02421887
Acronym / sponsor ID: MOXI / MOXI
Conditions: Male Infertility
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 171 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: University of North Carolina, Augusta University, Penn State University, University of California, San Francisco, University of Oklahoma, University of Pennsylvania
Study start: Dec 2015 (actual)
Primary completion: 11 Jun 2018 (actual)
Study completion: Dec 2018 (actual)
First posted: 21 Apr 2015 (estimated)
Results: Posted 4 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Antioxidant Supplement	Active comparator	Drug: Antioxidant SupplementTablet: Vitamin C, 500 mg; Vitamin D3, 1000 IU; Vitamin E, 400 IU; Folic Acid 1000 mcg; Zinc, 20 mg; Selenium 200 mcg; Lycopene, 10 mg; Capsule: Vitamin D3, 1000 IU, L-Carnitine, 1000 mg
Placebo	Placebo comparator	Other: Placebo

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

12 or more months of infertility (primary or secondary)
Heterosexual
Cohabitating and able to have regular intercourse
≥ 18 years of age
At least one abnormal semen parameter on a semen analysis within the past 6 months:

Key exclusion criteria (19 listed)

Couple:
Sperm concentration < 5 million/mL on screening semen analysis
Current use of a medication or drug that would affect reproductive function or metabolism (see Appendix C for list)
Current multivitamin or herb use (requires 1 month wash-out)
Current serious medical illnesses, such as cancer, heart disease, or cirrhosis

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Antioxidant SupplementAn antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine	Drug	Antioxidant Supplement
PlaceboPlacebo	Other	Placebo

Primary outcome

Live Birth Rate
Time frame: up to 15 months

9 secondary outcomes

Pregnancy Rate
Time frame: up to 7 months
Miscarriage Rate
Time frame: up to 9 months
Time to Pregnancy
Time frame: up to 7 months
Change in Total Motile Sperm Count
Time frame: baseline and 3 months
Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)
Time frame: Baseline and 3 months
Change in Semen Total Motility
Time frame: baseline and 3 months
Change in Sperm Concentration
Time frame: baseline and 3 months
Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria
Time frame: baseline and 3 months
Change in Total Sperm Count
Time frame: baseline and 3 months

Results and safety

Results posted to the registry on 4 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Antioxidant Supplement	85	68
Placebo	86	77

Primary outcome: Live Birth Rate

Time frame: up to 15 months. Number. Unit: percentage of live births

Measure	Antioxidant Supplement n = 85	Placebo n = 86
Value	15.3	22.1

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Event data was collected from start of study drug through 30 days after the last dose of study medication, on average 7 months. Subjects completed a monthly diary where they reported any adverse events. They were also queried by study staff at each study visit about any adverse events since the last visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Antioxidant Supplement	0 of 85 (0%)	28 of 85 (32.9%)	0 of 85
Placebo	0 of 86 (0%)	28 of 86 (32.6%)	0 of 86

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35106743Spitzer TL, Trussell JC, Coward RM, Hansen KR, Barnhart KT, Cedars MI, Diamond MP, Krawetz SA, Sun F, Zhang H, Santoro N, Steiner AZ. Biomarkers of Stress and Male Fertility. Reprod Sci. 2022 Apr;29(4):1262-1270. doi: 10.1007/s43032-022-00853-x. Epub 2022 Feb 1.
Derived from this study: PubMed 32111479Steiner AZ, Hansen KR, Barnhart KT, Cedars MI, Legro RS, Diamond MP, Krawetz SA, Usadi R, Baker VL, Coward RM, Huang H, Wild R, Masson P, Smith JF, Santoro N, Eisenberg E, Zhang H; Reproductive Medicine Network. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial. Fertil Steril. 2020 Mar;113(3):552-560.e3. doi: 10.1016/j.fertnstert.2019.11.008. Epub 2020 Feb 25.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.

Related trials for Male Infertility

Not yet recruitingPhase 3
Comparative Study of Post-Varicocelectomy Myo-inositol vs. Antioxidants vs. Surgery Alone in Infertile Men
Myo-inositol, Post Varicocelectomy
Active, not recruitingPhase 1/2
A Novel Aromatase Inhibitor, Leflutrozole, for Treatment of Non-Obstructive Azoospermia
Infertility Due to Azoospermia, Infertility, Male
Active, not recruiting
YO® Smartphone Home Sperm Test Versus Manual Semen Analysis in Egyptian Men
Semen Analysis, Male Infertility
Not yet recruitingPhase 4
Comparative Efficacy of Antioxidants Alone Versus Combined Therapy With SERMs or FSH in Normogonadotropic Idiopathic OAT Patients: A Randomized Controlled Trial
Oligoasthenoteratozoospermia, Male Infertility
Recruiting
Experimental Round Spermatid Injection (ROSI) to Treat Infertile Couples
Infertility, Male

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Esther Eisenberg, MD study director

Eunice Kennedy Shriver National Institue of Child Health and Human Development

Nanette Santoro, MD study chair

University of Colorado, Denver

Anne Z Steiner, MD principal investigator

University of North Carolina

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Antioxidant Supplement in people with Male Infertility, run by Yale University at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Live Birth Rate (time frame: up to 15 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02421887, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019; AzTrials last refreshed its copy on 6 Nov 2026.