Impact of Antioxidant Treatment on DNA Fragmentation Index (Androferti)

• ClinicalTrials.gov Identifier: NCT03466229
• Recruitment Status: Completed
• First Posted: March 15, 2018
• Last Update Posted: March 16, 2018
• Sponsor: Region Skane
• Collaborators: Q-Pharma; Octean
• Information provided by (Responsible Party): Aleksander Giwercman, Region Skane

Study Description

Brief Summary:

Increased sperm DNA Fragmentation Index implies decreased male fertility in vivo and in vitro. There is need for developing new strategies for improvement of male fertility. The study aims to investigate whether high sperm DNA Integration Index can be treated by use of antioxidants.

Condition or disease	Intervention/treatment	Phase
Male Infertility	Dietary Supplement: Androferti; Dietary Supplement: Placebo	Not Applicable

Detailed Description:

In the Western world, approximately 15-20% of couples experience infertility problems during their reproductive life. In this context ´'infertility' is defined as 12 months of unprotected intercourse without getting pregnant.

Although there is limited access to reliable diagnostic methods, it is assumed that in at least 50% of all cases 'male subfertility' is a contributing or the main cause of the infertility of the couple. The gold standard in assessment of male reproductive function is standard semen analysis including evaluation of sperm number, motility and morphology. Although efforts have been made in to improve and standardise the methodology for semen analysis, there are no well established cut off levels for sperm concentration, motility or morphology which accurately predict the chance of pregnancy or indicate which assisted reproductive technique (ART) - the most frequent therapy for infertility- will ultimately be the most effective. This lack of diagnostic tools is not only hampering proper management of infertility but also represents a serious limitation in relation to the understanding of biological underpinnings of the disorder and as a consequence, the development of cause related treatment modalities.

Although various novel alternative methods of assessing semen quality have been developed, so far, none have contributed to or altered our clinical approach to the treatment of infertile couples. During the passed two decades a lot of attention has been paid to impairment of sperm DNA integrity as a possible cause of male subfertility. There are different techniques currently available for the assessment of sperm DNA integrity e.g. Sperm Chromatin Structure Assay (SCSA®), Comet, TUNEL and sperm chromatin dispersion test. Generally, the use of these tests has shown an increased proportion of sperm with fragmented DNA structure among subfertile men as compared to proven fertile or men from general population. Although measuring different characteristics of the status of sperm DNA (e.g. presence of single and double strand breaks, propensity to damage and probable cause of the fragmentation), comparisons of the results obtained with two or more of these tests show a correlation coefficient of a magnitude 0.4 to 0.6, indicating that, although not completely overlapping, the tests to a certain extent assess some of the same characteristics of sperm DNA. Another interesting finding is that there is only a weak to moderate correlation between standard sperm parameters and measures of DNA integrity, the level of association (correlation coefficient ~ 0.6) the most pronounced being for motility. This means that assessment of sperm chromatin integrity adds to the information obtained by standard semen analysis.

The most appraised, standardised and studied of the sperm nDNA tests is the SCSA® which is based on a very well defined protocol for handling of samples and subsequent data analysis. The robustness of the techniques was exemplified by a comparison of the SCSA® analysis of almost 200 samples results performed by two independent laboratories which found a correlation coefficient of 0.9 with mean difference between the DNA Fragmentation Index (DFI) results of about 1%. A further advantage of the SCSA® method over the remaining assessment techniques is the relatively large number of studies that have utilised the technique in clinical settings constituting a considerable record of the method's performance in predicting fertility outcome.

Briefly, these data indicate that the chance of spontaneous pregnancy decreases at DFI levels above 20% and approaches zero if DFI exceeds 30%. This is also true for Intrauterine insemination (IUI). However, it seems that even spermatozoa from samples with high DFI can be used for in vitro fertilisation by standard IVF or ICSI, with some data suggesting that ICSI might actually be more efficient using samples with high (>30%) DFI. A finding, which may at first appear paradoxical but may be a reflection of the relative probability of fortuitously selecting a sperm with intact DNA. The data regarding fertilisation rate, embryo quality and risk of miscarriage in relation to DFI are also conflicting.

The biological mechanisms responsible for DNA strand breaks and other types of impairment of sperm DNA integrity are not completely known. Amongst others incomplete DNA repair during spermiogenesis, abortive apoptosis and/or increased level of oxidative stress have been suggested as possible options .

The overall aim of this project is to evaluate effect of restoring oxidant balance using Androferti, (Q Pharma Laboratories; Alicante, Spain) on sperm DNA integrity in subfertile men with high level of DFI.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double blind randomised placebo controlled study
• Masking: Single (Investigator)
• Masking Description: The active compound and placebo are given a number and the list linking this number to the type of preparation (placebo or active compound) is stored by one of the sponsors (Octean)
• Primary Purpose: Treatment
• Official Title: Impact of Antioxidant (Androferti) Treatment on Sperm DNA Integrity
• Actual Study Start Date: July 1, 2015
• Actual Primary Completion Date: December 31, 2016
• Actual Study Completion Date: December 31, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Antioxidant; Androferti - 1 twice per day	Dietary Supplement: Androferti
Placebo Comparator: Placebo; Placebo - 1 twice per day	Dietary Supplement: Placebo

Outcome Measures

Primary Outcome Measures :

1. DFI_3 [ Time Frame: Change in DNA Fragmentation Index from Baseline to 3 months ]
   3_month_change_DNA Fragmentation Index assessed by Sperm Chromatin
2. DFI_6 [ Time Frame: Change in DNA Fragmentation Index from Baseline to 6 months ]
   6_month_change_DNA Fragmentation Index assessed by Sperm Chromatin Structure Assay

Secondary Outcome Measures :

1. Concentration_3 [ Time Frame: Change in sperm concentration from baseline to 3 months in millions/mL ]
   Change sperm concentration 3 months
2. Concentration_6 [ Time Frame: Change in sperm concentration from baseline to 6 months in millions/mL ]
   Change sperm concentration 6 months
3. Motility_3 [ Time Frame: Change in sperm motility from baseline to 3 months in % ]
   Change sperm motility 3 months
4. Motility_6 [ Time Frame: Change in sperm motility from baseline to 6 months in % ]
   Change sperm motility 6 months
5. Morphology_3 [ Time Frame: Change in sperm morphology from baseline to 3 months in % ]
   Change sperm morphology 3 months
6. Morphology_6 [ Time Frame: Change in sperm morphology from baseline to 6 months in % ]
   Change sperm morphology 6 months

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Men able to deliver semen sample and investigated due to infertility
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Referred due to infertility
2. Age: 18-50 years,
3. Non-smoking,
4. Sperm DNA Fragmentation Index >25%

Exclusion Criteria:

1. Body mass index (BMI) ≥30,
2. FSH outside the normal range of 2-8 IU/L,g)
3. LH outside the normal range of 2-10 IU/L,
4. T < 10nmol/L
5. Treated with antihypertensive drugs, hormones, statins, psychotropic drugs, or oral cortisone for the last six months,
6. History of anabolic steroids use,
7. Taking antioxidant supplementation the last six months.

Contacts and Locations

No Contacts or Locations Provided

More Information

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

Stenqvist A, Oleszczuk K, Leijonhufvud I, Giwercman A. Impact of antioxidant treatment on DNA fragmentation index: a double-blind placebo-controlled randomized trial. Andrology. 2018 Nov;6(6):811-816. doi: 10.1111/andr.12547. Epub 2018 Oct 8.

• Responsible Party: Aleksander Giwercman, Professor, Region Skane
• ClinicalTrials.gov Identifier: NCT03466229
• Other Study ID Numbers: Androferti
• First Posted: March 15, 2018
• Last Update Posted: March 16, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Plan to share IPD has not yet been discussed

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aleksander Giwercman, Region Skane:

sperm DNA strand breaks; antioxidants

Additional relevant MeSH terms:

Infertility; Infertility, Male