To Evaluate the Effect of Reveratrol,Folic Acid, Vitamin D, Vitamin B12 and B6 in Male Infertility

Evaluation of Treatment With Trans-resveratrol, Folic Acid, Vitamin D, Vitamin B12 and B6 in Men With Infertility

The objective of this study is to evaluate the impact of the Genante(TM) on the spermiogram parameters in infertile male patients

Study Overview

• Status: Unknown
• Conditions: Male Infertility
• Intervention / Treatment: Dietary supplement: Genante

Detailed Description

This is a single-centre prospective observational study. Twenty infertile male patients.

Inclusion criteria are:

Age:18-50 years oligozoospermia: < 5 million spermatozoa/mL; asthenozoospermia: < 32% progressive motile spermatozoa; teratozoospermia: < 4% normal forms.

Esclusion criteria:

Patients with azoospermia, who smoke, use drugs, drugs with proven fertility toxicity, exposed to any environmental or occupational toxic substances, radiation or heat; with orchitis secondary to mumps, sexually transmitted diseases, history of cryptorchidism, previous testicular torsion, genitourinary anomalies, alterations of the epididymis or deferens; and inguinal surgery

Pretreatment evaluation included:

Semen analysis Hormonal determinations:follicle-stimulating hormone (FSH) and luteinising hormone (LH) total Testosterone Total,estradiol, prolactina, 25-OH-Vitamin D3); scrotal ultrasound prostatic transrectal ultrasound

Outocmes measures (baseline, at 1 and 6 months):

• Semen volume (mL)
• Total sperm number (106/ejaculate)
• Sperm concentration (106/mL)
• Total motility (PR + NP)
• Progressive motility (PR, %)
• Vitality (live spermatozoa, %)
• Sperm morphology (normal forms, %)
• Ph
• FSH
• LH
• Testosterone totale
• Estradiol
• Prolactiona
• 25-OH-Vitamin D3
• scrotal ultrasound
• prostatic transrectal ultrasound

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisabetta Costantini, Professor; Phone Number: 3283620614; Email: elisabetta.costantini@unipg.it
• Study Contact Backup: Name: Ester Illiano, MD; Phone Number: 3283620614; Email: ester.illiano@inwind.it

Study Locations

• Italy
  • Terni, Italy, 05100
    • Recruiting
    • Elisabetta Costantini
    • Contact: Elisabetta Costantini, Professor; Phone Number: 3283620614; Email: elisabetta.costantini@unipg.it
    • Contact: Ester Illiano, MD; Phone Number: 3283620614; Email: ester.illiano@inwind.it
    • Sub-Investigator: Ester Illiano, MD
    • Principal Investigator: Elisabetta Costantini, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• male 18-50 years
• oligozoospermia: < 5 million spermatozoa/mL;
• asthenozoospermia: < 32% progressive motile spermatozoa;
• teratozoospermia: < 4% normal forms.

Exclusion Criteria:

• azoospermia
• smoke
• use drugs
• use drugs with proven fertility toxicity
• exposition to any environmental or occupational toxic substances
• exposition to radiation or heat
• orchitis secondary to mumps
• sexually transmitted diseases
• history of cryptorchidism
• previous testicular torsion
• genitourinary anomalies
• alterations of the epididymis or deferens
• inguinal surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Genante (Tm); Genante tablets One tablet in the morning and one tablet in the evening for 3 months	Dietary supplement: Genante; A dietary supplement for male infertility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Semen volume at 1 month	semen volume in semen analysis	1 month
Change from 1month Semen volume at 6 months	semen volume in semen analysis	6 months
Change from baseline Total sperm number at 1 month	total sperm number in semen analysis	1 month
Change from 1 month Total sperm number at 6 months	total sperm number in semen analysis	6 months
Change from baseline Sperm concentration at 1 month	Sperm concentration in semen analysis	1 month
Change from 1 month Sperm concentration at 6 months	Sperm concentration in semen analysis	6 months
Change from baseline Total Motility at 1 month	total motility of spermatozoa in semen analysis	1 month
Change from 1 month Total Motility at 6 months	total motility of spermatozoa in semen analysis	6 months
Change from baseline Progressive motility at 1 month	Porgressive motility of spermatozoa in semen analysis	1 month
Change from 1 month Progressive motility at 6 months	Progressive motility of spermatozoa in semen analysis	6 months
Change from baseline Vitality at 1 month	live spermatozoa	1 month
Change from 1 month Vitality at 6 months	live spermatozoa	6 months
Change from baseline Sperm morphology at 1 month	normal forms of spermatozoa	1 month
Change from 1 month Sperm morphology at 6 months	normal forms of spermatozoa	6 months
Change from baseline FSH at 1 month	plasmatic evaluation of FSH	1 month
Change from 1 month FSH at 6 months	plasmatic evaluation of FSH	6 months
Change from baseline LH at 1 month	Plasmatic evaluation of LH	1 month
Change from 1 month LH at 6 months	Plasmatic evaluation of LH	6 months
Change from baseline Total testosterone at 1 month	plasmatic evaluation of total testosterone	1 month
Change from 1 month Total testosterone at 6 months	plasmatic evaluation of total testosterone	6 months
Change from baseline Prolactina at 1 month	plasmatic evaluation of prolactina	1 month
Change from 1 month Prolactina at 6 months	plasmatic evaluation of prolactina	6 months
Change from baseline 25-OH-Vitamin D3 at 1 month	plasmatic evaluation of 25-OH-Vitamin D3	1 month
Change from 1 month 25-OH-Vitamin D3 at 6 months	plasmatic evaluation of 25-OH-Vitamin D3	6 months
Change from baseline Scrotal ultrasound at 1 month	testis volume and vas deferens by ultrasound	1 month
Change from 1 month Scrotal ultrasound at 6 months	testis volume and vas deferens by ultrasound	6 months
Change from baseline Trans rectal Prostatic ultrasound at 1 month	prostate volume and morphology by ultrasound	1 month
Change from 1 month Trans rectal Prostatic ultrasound at 6 months	prostate volume and morphology by ultrasound	6 months
Change from baseline estradiol at 1 month	plasmatic evaluation of esatrdiol	1 month
Change from 1 month estradiol at 6 months	plasmatic evaluation of esatrdiol	6 months

Collaborators and Investigators

• Sponsor: University Of Perugia
• Collaborators: Ester Illiano, MD
• Investigators: Study Director: Ester Illiano, MD, University Of Perugia

Publications and helpful links

General Publications

• Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004 Jun;8(6):616-27. doi: 10.1016/s1472-6483(10)61641-0.
• Griveau JF, Le Lannou D. Reactive oxygen species and human spermatozoa: physiology and pathology. Int J Androl. 1997 Apr;20(2):61-9. doi: 10.1046/j.1365-2605.1997.00044.x.
• Aitken RJ. Free radicals, lipid peroxidation and sperm function. Reprod Fertil Dev. 1995;7(4):659-68. doi: 10.1071/rd9950659.
• de Lamirande E, Leclerc P, Gagnon C. Capacitation as a regulatory event that primes spermatozoa for the acrosome reaction and fertilization. Mol Hum Reprod. 1997 Mar;3(3):175-94. doi: 10.1093/molehr/3.3.175.
• Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W. The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity. Hum Reprod. 1998 May;13(5):1240-7. doi: 10.1093/humrep/13.5.1240. Erratum In: Hum Reprod 1998 Nov;13(11):3284.
• Erben RG, Soegiarto DW, Weber K, Zeitz U, Lieberherr M, Gniadecki R, Moller G, Adamski J, Balling R. Deletion of deoxyribonucleic acid binding domain of the vitamin D receptor abrogates genomic and nongenomic functions of vitamin D. Mol Endocrinol. 2002 Jul;16(7):1524-37. doi: 10.1210/mend.16.7.0866.
• Hammoud AO, Meikle AW, Peterson CM, Stanford J, Gibson M, Carrell DT. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl. 2012 Nov;14(6):855-9. doi: 10.1038/aja.2012.77. Epub 2012 Oct 8.
• Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA, Steegers-Theunissen RP. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertil Steril. 2002 Mar;77(3):491-8. doi: 10.1016/s0015-0282(01)03229-0.
• Chen Q, Ng V, Mei J, Chia SE. [Comparison of seminal vitamin B12, folate, reactive oxygen species and various sperm parameters between fertile and infertile males]. Wei Sheng Yan Jiu. 2001 Mar;30(2):80-2. Chinese.
• Das S, Lin HS, Ho PC, Ng KY. The impact of aqueous solubility and dose on the pharmacokinetic profiles of resveratrol. Pharm Res. 2008 Nov;25(11):2593-600. doi: 10.1007/s11095-008-9677-1. Epub 2008 Jul 16. Erratum In: Pharm Res. 2008 Dec;25(12):2983.
• Amri A, Chaumeil JC, Sfar S, Charrueau C. Administration of resveratrol: What formulation solutions to bioavailability limitations? J Control Release. 2012 Mar 10;158(2):182-93. doi: 10.1016/j.jconrel.2011.09.083. Epub 2011 Sep 25.
• Orihuela-Campos RC, Tamaki N, Mukai R, Fukui M, Miki K, Terao J, Ito HO. Biological impacts of resveratrol, quercetin, and N-acetylcysteine on oxidative stress in human gingival fibroblasts. J Clin Biochem Nutr. 2015 May;56(3):220-7. doi: 10.3164/jcbn.14-129. Epub 2015 Mar 28.
• Liu J, Yi L, Xiang Z, Zhong J, Zhang H, Sun T. Resveratrol attenuates spinal cord injury-induced inflammatory damage in rat lungs. Int J Clin Exp Pathol. 2015 Feb 1;8(2):1237-46. eCollection 2015.
• Illiano E, Trama F, Zucchi A, Iannitti RG, Fioretti B, Costantini E. Resveratrol-Based Multivitamin Supplement Increases Sperm Concentration and Motility in Idiopathic Male Infertility: A Pilot Clinical Study. J Clin Med. 2020 Dec 11;9(12). pii: E4017. doi: 10.3390/jcm9124017.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2019
• Primary Completion (Anticipated): March 20, 2019
• Study Completion (Anticipated): April 30, 2019

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: March 3, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 3, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Vitamin B12; Folic acid; Vitamin B6; Male infertility; Reveratrol
• Additional Relevant MeSH Terms: Infertility; Infertility, Male
• Other Study ID Numbers: RESV1; 3310 (CEAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No