Males, Antioxidants, and Infertility Trial

NCT02421887 | Completed Phase 2 Results DMC

• 1 other identifier: MOXI
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 10

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

Outcome Measures

Primary Outcomes (1)

• Live Birth Rate

  up to 15 months

Secondary Outcomes (9)

• Pregnancy Rate

  up to 7 months

• Miscarriage Rate

  up to 9 months

• Time to Pregnancy

  up to 7 months

• Change in Total Motile Sperm Count

  baseline and 3 months

• Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)

  Baseline and 3 months

Study Arms (2)

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

Drug: Antioxidant Supplement

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Antioxidant Supplement DRUG

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

Antioxidant Supplement

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• University of North Carolina: collaborator
• Augusta University: collaborator
• Penn State University: collaborator
• University of California, San Francisco: collaborator
• University of Oklahoma: collaborator
• University of Pennsylvania: collaborator

Study Sites (10)

Keck School of Medicine of University of Southern California

Los Angeles, California, 90089, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Stanford University

Sunnyvale, California, 94087, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Wayne State University

Southfield, Michigan, 48034, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center - Women's Institute

Charlotte, North Carolina, 28204, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• 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.

  PMID: 35106743 DERIVED

• 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.

  PMID: 32111479 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Results Point of Contact

• Title: Esther Eisenberg, NICHD Project Scientist
• Organization: NICHD

esther.eisenberg@nih.gov

301-496-6516

Study Officials

• Esther Eisenberg, MD

  Eunice Kennedy Shriver National Institue of Child Health and Human Development

  STUDY DIRECTOR

• Nanette Santoro, MD

  University of Colorado, Denver

  STUDY CHAIR

• Anne Z Steiner, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

• Michael P Diamond, MD

  Augusta University

  STUDY DIRECTOR

• Richard S Legro, MD

  Penn State University

  STUDY DIRECTOR

• Marcelle Cedars, MD

  University of California, San Francisco

  STUDY DIRECTOR

• Karl R Hansen, MD

  University of Oklahoma

  STUDY DIRECTOR

• Christos Coutifaris, MD

  University of Pennsylvania

  STUDY DIRECTOR

• Heping Zhang, PhD

  Yale University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: April 21, 2015
• Study Start: December 1, 2015
• Primary Completion: June 11, 2018
• Study Completion: December 1, 2018
• Last Updated: September 4, 2019
• Results First Posted: September 4, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Following publication of the primary publication and when the de-identified data have been put into a format that is acceptable for DASH submission.

Locations

US (10)