Trial Outcomes & Findings for Males, Antioxidants, and Infertility Trial (NCT NCT02421887)

NCT ID: NCT02421887

Last Updated: 2019-09-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 171 participants
• Primary outcome timeframe: up to 15 months
• Results posted on: 2019-09-04

Participant Flow

Participant milestones

Measure	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	Placebo Placebo: Placebo
Overall Study STARTED	85	86
Overall Study COMPLETED	68	77
Overall Study NOT COMPLETED	17	9

Reasons for withdrawal

Measure	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	Placebo Placebo: Placebo
Overall Study Lost to Follow-up	5	0
Overall Study Withdrawal by Subject	8	5
Overall Study Physician Decision	2	4
Overall Study Adverse Event	2	0

Baseline Characteristics

Males, Antioxidants, and Infertility Trial

Baseline characteristics by cohort

Measure	Antioxidant Supplement n=85 Participants 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	Placebo n=86 Participants Placebo: Placebo	Total n=171 Participants Total of all reporting groups
Age, Continuous	34.0 years n=93 Participants	34.0 years n=4 Participants	34.0 years n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	85 Participants n=93 Participants	86 Participants n=4 Participants	171 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=93 Participants	5 Participants n=4 Participants	12 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=93 Participants	78 Participants n=4 Participants	150 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=93 Participants	3 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Asian	7 Participants n=93 Participants	2 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants	7 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) White	63 Participants n=93 Participants	69 Participants n=4 Participants	132 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=93 Participants	5 Participants n=4 Participants	13 Participants n=27 Participants

PRIMARY outcome

Timeframe: up to 15 months

Outcome measures

Measure	Antioxidant Supplement n=85 Participants 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	Placebo n=86 Participants Placebo: Placebo
Live Birth Rate	15.3 percentage of live births	22.1 percentage of live births

SECONDARY outcome

Timeframe: up to 7 months

Outcome measures

Measure	Antioxidant Supplement n=85 Participants 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	Placebo n=86 Participants Placebo: Placebo
Pregnancy Rate	18 Participants	26 Participants

SECONDARY outcome

Timeframe: up to 9 months

Population: Miscarriage rate is calculated per number of participants who became pregnant.

miscarriages per total number of pregnancies

Outcome measures

Measure	Antioxidant Supplement n=18 Participants 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	Placebo n=26 Participants Placebo: Placebo
Miscarriage Rate	4 miscarriages	5 miscarriages

SECONDARY outcome

Timeframe: up to 7 months

Population: Time to pregnancy is calculated only for subjects who obtained pregnancy during the trial.

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.

Outcome measures

Measure	Antioxidant Supplement n=18 Participants 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	Placebo n=25 Participants Placebo: Placebo
Time to Pregnancy	103.5 days Standard Deviation 62.3	123.5 days Standard Deviation 59.9

SECONDARY outcome

Timeframe: baseline and 3 months

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

Samples will be assessed using a standard semen analysis

Outcome measures

Measure	Antioxidant Supplement n=82 Participants 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	Placebo n=82 Participants Placebo: Placebo
Change in Total Motile Sperm Count	-4.0 million sperm per mL Interval -13.2 to 9.9	1.5 million sperm per mL Interval -11.8 to 15.4

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Antioxidant Supplement n=73 Participants 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	Placebo n=74 Participants Placebo: Placebo
Change in Deoxyribonucleic Acid (DNA) Fragmentation Index (DFI)	18.7 percentage of damaged DNA to total DNA Interval 14.3 to 28.3	21.1 percentage of damaged DNA to total DNA Interval 14.1 to 28.6

SECONDARY outcome

Timeframe: baseline and 3 months

Samples assessed using a standard semen analysis

Outcome measures

Measure	Antioxidant Supplement n=82 Participants 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	Placebo n=82 Participants Placebo: Placebo
Change in Semen Total Motility	-1.6 percentage of sperm with any motility Standard Deviation 16.0	-1.1 percentage of sperm with any motility Standard Deviation 13.7

SECONDARY outcome

Timeframe: baseline and 3 months

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

Samples assessed using a standard semen analysis

Outcome measures

Measure	Antioxidant Supplement n=82 Participants 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	Placebo n=82 Participants Placebo: Placebo
Change in Sperm Concentration	-4.0 million sperm per mL Interval -12.0 to 5.7	2.4 million sperm per mL Interval -9.0 to 15.5

SECONDARY outcome

Timeframe: baseline and 3 months

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

Samples assessed using a standard semen analysis

Outcome measures

Measure	Antioxidant Supplement n=55 Participants 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	Placebo n=55 Participants Placebo: Placebo
Change in Normal Morphology of Semen, Using World Health Organization (WHO) 5 Criteria	0 percentage of sperm with normal morpholo Interval -2.0 to 1.0	0 percentage of sperm with normal morpholo Interval -2.0 to 1.0

SECONDARY outcome

Timeframe: baseline and 3 months

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

Samples assessed using a standard semen analysis

Outcome measures

Measure	Antioxidant Supplement n=82 Participants 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	Placebo n=82 Participants Placebo: Placebo
Change in Total Sperm Count	-10.6 million sperm per sample Interval -32.5 to 12.6	1.6 million sperm per sample Interval -21.8 to 42.9

Adverse Events

Antioxidant Supplement

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Antioxidant Supplement n=85 participants at risk 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	Placebo n=86 participants at risk Placebo: Placebo
Gastrointestinal disorders Abdominal pain	0.00% 0/85 • 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.	4.7% 4/86 • 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.
Gastrointestinal disorders Dyspepsia	4.7% 4/85 • 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.	2.3% 2/86 • 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.
General disorders Headache	17.6% 15/85 • 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.	8.1% 7/86 • 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.
Infections and infestations Nasopharyngitis	4.7% 4/85 • 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.	8.1% 7/86 • 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.
Gastrointestinal disorders Nausea	1.2% 1/85 • 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.	4.7% 4/86 • 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.
Infections and infestations Upper Respiratory Infection	4.7% 4/85 • 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.	4.7% 4/86 • 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.

Additional Information

Esther Eisenberg, NICHD Project Scientist

NICHD

Phone: 301-496-6516

Email: esther.eisenberg@nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place