Males, Antioxidants, and Infertility Trial (MOXI)

• ClinicalTrials.gov Identifier: NCT02421887
• Recruitment Status: Completed
• First Posted: April 21, 2015
• Results First Posted: September 4, 2019
• Last Update Posted: September 4, 2019
• Sponsor: Yale University
• Collaborators: University of North Carolina; Augusta University; Penn State University; University of California, San Francisco; University of Oklahoma; University of Pennsylvania
• Information provided by (Responsible Party): Yale University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Male Infertility	Drug: Antioxidant Supplement; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 171 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Males, Antioxidants, and Infertility (MOXI) Trial
• Actual Study Start Date: December 2015
• Actual Primary Completion Date: June 11, 2018
• Actual Study Completion Date: December 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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	Drug: Antioxidant Supplement; An antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine
Placebo Comparator: Placebo	Other: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Live Birth Rate [ Time Frame: up to 15 months ]

Secondary Outcome Measures :

1. Pregnancy Rate [ Time Frame: up to 7 months ]
2. Miscarriage Rate [ Time Frame: up to 9 months ]
   miscarriages per total number of pregnancies
3. Time to Pregnancy [ Time Frame: up to 7 months ]
   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.
4. Change in Total Motile Sperm Count [ Time Frame: baseline and 3 months ]
   Samples will be assessed using a standard semen analysis
5. Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI) [ Time Frame: Baseline and 3 months ]
   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.
6. Change in Semen Total Motility [ Time Frame: baseline and 3 months ]
   Samples assessed using a standard semen analysis
7. Change in Sperm Concentration [ Time Frame: baseline and 3 months ]
   Samples assessed using a standard semen analysis
8. Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria [ Time Frame: baseline and 3 months ]
   Samples assessed using a standard semen analysis
9. Change in Total Sperm Count [ Time Frame: baseline and 3 months ]
   Samples assessed using a standard semen analysis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:Couple

• 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

Contacts and Locations

Locations

United States, California

Keck School of Medicine of University of Southern California

Los Angeles, California, United States, 90089

University of California San Francisco

San Francisco, California, United States, 94115

Stanford University

Sunnyvale, California, United States, 94087

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

United States, Michigan

Wayne State University

Southfield, Michigan, United States, 48034

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Carolinas Medical Center - Women's Institute

Charlotte, North Carolina, United States, 28204

United States, Oklahoma

University of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Pennsylvania State University

Hershey, Pennsylvania, United States, 17033

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Yale University

University of North Carolina

Augusta University

Penn State University

University of California, San Francisco

University of Oklahoma

University of Pennsylvania

Investigators

• Study Director: Esther Eisenberg, MD; Eunice Kennedy Shriver National Institue of Child Health and Human Development
• Study Chair: Nanette Santoro, MD; University of Colorado, Denver
• Principal Investigator: Anne Z Steiner, MD; University of North Carolina
• Study Director: 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 Documents (Full-Text)

Documents provided by Yale University:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] October 12, 2016

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02421887
• Other Study ID Numbers: MOXI
• First Posted: April 21, 2015
• Results First Posted: September 4, 2019
• Last Update Posted: September 4, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.
• 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.

Additional relevant MeSH terms:

Infertility; Infertility, Male; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs