Males, Antioxidants, and Infertility Trial

Males, Antioxidants, and Infertility (MOXI) Trial

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02421887

Acronym

MOXI

Enrollment

171

Registered

2015-04-21

Start date

2015-12-31

Completion date

2018-12-31

Last updated

2019-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Male Infertility

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.

Interventions

DRUGAntioxidant Supplement

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

OTHERPlacebo

Placebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Live Birth Rate	up to 15 months

Secondary

Measure	Time frame	Description
Miscarriage Rate	up to 9 months	miscarriages per total number of pregnancies
Time to Pregnancy	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.
Change in Total Motile Sperm Count	baseline and 3 months	Samples will be assessed using a standard semen analysis
Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)	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.
Pregnancy Rate	up to 7 months	—
Change in Sperm Concentration	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Total Sperm Count	baseline and 3 months	Samples assessed using a standard semen analysis
Change in Semen Total Motility	baseline and 3 months	Samples assessed using a standard semen analysis

Countries

United States

Participant flow

Participants by arm

Arm	Count
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 Antioxidant Supplement: An antioxidant combination including Vitamin C, Vitamin E, folic acid, selenium, zinc, and L-carnitine	85
Placebo Placebo: Placebo	86
Total	171

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Lost to Follow-up	5	0
Overall Study	Physician Decision	2	4
Overall Study	Withdrawal by Subject	8	5

Baseline characteristics

Characteristic	Placebo	Total	Antioxidant Supplement
Age, Continuous	34.0 years	34.0 years	34.0 years
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	12 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants	150 Participants	72 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants	9 Participants	6 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) Asian	2 Participants	9 Participants	7 Participants
Race (NIH/OMB) Black or African American	7 Participants	13 Participants	6 Participants
Race (NIH/OMB) More than one race	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants	13 Participants	8 Participants
Race (NIH/OMB) White	69 Participants	132 Participants	63 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	86 Participants	171 Participants	85 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 85	0 / 86
other Total, other adverse events	28 / 85	28 / 86
serious Total, serious adverse events	0 / 85	0 / 86

Outcome results

Primary

Live Birth Rate

Time frame: up to 15 months

Arm	Measure	Value (NUMBER)
Antioxidant Supplement	Live Birth Rate	15.3 percentage of live births
Placebo	Live Birth Rate	22.1 percentage of live births

Secondary

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.

Time frame: Baseline and 3 months

Population: Participants for which semen samples were analyzed for DFI at both Baseline and Month 3 visit are included in this outcome measure.

Arm	Measure	Value (MEAN)
Antioxidant Supplement	Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)	18.7 percentage of damaged DNA to total DNA
Placebo	Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)	21.1 percentage of damaged DNA to total DNA

Secondary