Males, Antioxidants, and Infertility Trial

NCT ID: NCT02421887

Last Updated: 2019-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 171 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-12-31

Brief Summary

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Antioxidant Supplement

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

Group Type: ACTIVE_COMPARATOR

Antioxidant Supplement

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

Antioxidant Supplement

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

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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:

• 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.

Exclusion Criteria

• 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)
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of North Carolina

OTHER

Sponsor Role: collaborator

Augusta University

OTHER

Sponsor Role: collaborator

Penn State University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of Oklahoma

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esther Eisenberg, MD

Role: STUDY_DIRECTOR

Eunice Kennedy Shriver National Institue of Child Health and Human Development

Nanette Santoro, MD

Role: STUDY_CHAIR

University of Colorado, Denver

Anne Z Steiner, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Michael P Diamond, MD

Role: STUDY_DIRECTOR

Augusta University

Richard S Legro, MD

Role: STUDY_DIRECTOR

Penn State University

Marcelle Cedars, MD

Role: STUDY_DIRECTOR

University of California, San Francisco

Karl R Hansen, MD

Role: STUDY_DIRECTOR

University of Oklahoma

Christos Coutifaris, MD

Role: STUDY_DIRECTOR

University of Pennsylvania

Heping Zhang, PhD

Role: STUDY_DIRECTOR

Yale University

Locations

Keck School of Medicine of University of Southern California

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

Stanford University

Sunnyvale, California, United States

Augusta University

Augusta, Georgia, United States

Wayne State University

Southfield, Michigan, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Carolinas Medical Center - Women's Institute

Charlotte, North Carolina, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

Pennsylvania State University

Hershey, Pennsylvania, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35106743 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32111479 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

http://c2s2.yale.edu/rmn/

Related Info

Other Identifiers

MOXI

Identifier Type: -

Identifier Source: org_study_id