Male InfertilityEarly Phase 1NCT04541459
Validation of New Devices Against Ambient Electromagnetic Radiation
A Early Phase 1 study testing new device against ambient electromagnetic radiation in people with Male Infertility, run by Waveguard GmbH at 1 site in United States.
Trial summary
Project Summary Cell phones have become indispensable devices in the investigator's daily life. These phones operate between 400 and 2000 MHz frequency bands and emit radiofrequency electromagnetic waves (EMW). Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Male Infertility
- What is being tested?
- new device against ambient electromagnetic radiation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2020to 1 Apr 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normal healthy men with normozoospermic semen parameters.
Who cannot join
- Subjects with a history of smoking
- Chewing tobacco
- Alcohol consumption
- Antioxidant supplementation
- Orchitis, varicocele, tuberculosis, diabetes mellitus, and hypertension
- Viral/bacterial infection in the past 4 weeks
- History of cardiac, neural, or nephrotic disease
- Family history of any genetic disease
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
American Center for Reproductive Medicine, Cleveland Clinic
Cleveland, Ohio, 44195
Ashok Agarwal, PhD, 216-444-9485, agarwaa@ccf.org
Ashok Agarwal, PhD
About this study
Official title: Validation of New Devices Against Ambient Electromagnetic Radiation: A Randomized Double Blind Controlled Study
Project Summary Cell phones have become indispensable devices in the investigator's daily life. These phones operate between 400 and 2000 MHz frequency bands and emit radiofrequency electromagnetic waves (EMW). Radio-frequency electro-magnetic field exposure from cell phones or other sources of microwaves have deleterious effects on sperm parameters (like sperm count, morphology, motility). Further, EMW radiation emitted by mobile phones affects cells and organelles, and results in disorientation of charged molecules within the cytosol and a distortion of electron flow along the internal membranes of the cells. These cellular changes results in the generation of ROS leading to oxidative stress, which in turn results in radiation-induced sperm DNA fragmentation.
Radiation shield can help provide protection from high levels of EMW radiations deflecting, diverting, and absorbing the radiation between the user and the source. A new EMW radiation shield, Qi-Shield device developed by Waveguard GmbH (Bautzen, Germany) provides protection against the radiations emitted by the smartphone and laptop devices. Qi-Shield utilizes conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation.
Read more
Study Aims:
To evaluate the changes in the semen parameters from the use of Qi-Shield device in sham (control) and user groups To determine the molecular changes pertaining to sperm proteins from the use of Qi-Shield device in sham (control) and user groups
Significance The negative health consequences of EMWs have been documented across a wide range of device types, exposure frequencies and doses (Giuliani, 2010), at field strengths substantially below the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for permissible exposures. In the absence of a revision in the ICNIRP guidelines, near-term public exposures to EMWs will most certainly continue to increase, despite the scientific evidence suggesting more careful review and recommendations to limit exposure to electromagnetic fields as much as possible. At present, there is no veritable means for counteracting the negative health consequences of human-made EMWs, revealing an unmet need for a means of protecting from or ameliorating the negative effects of EMWs, and the need for devising strategies for creating safer living and working environments in a time of increasing EMW exposures.
Positive results in this study would demonstrate a means of counteracting negative effects on human sperm due to EMWs. Documentation of protection due to the Qi-Shield devices would show proof of principle that a low-cost passive device, portable and without battery or mains power, can provide improvements in human sperm parameters, with promise for a means of counteracting EMW-reduced fertility in large numbers of people. Confirmation of changes on protein expression would provide data needed to identify specific pathways of action, insight that is necessary for a more detailed understanding of the mechanisms of action of the EMW protection effect. Taken together, these results would suggest further lines of study in EMW protection, and provide clinical support for the adoption of EMW-protecting devices in the home and workplace.
Read the detailed description
Normal healthy men enrolled in the study will be asked to provide semen specimens prior to the use of device. Samples will be produced with a minimum of 48-72 hours of abstinence. Further, the subjects will be blindly assigned with either sham Qi-Shield or Qi-Shield device and will be instructed to use the device for a duration of 8 weeks .Semen samples will be provided by the subjects at 0, 4 and 8 weeks interval.
Group 1 study subjects will be provided with sham Qi-Shield device, whereas Group 2 study subjects with be provided with actual Qi-Shield device. Each user will be provided with a small carrier bag to accommodate the device during their travel. The participants are advised to keep the device within 3 meters of range as per the manufacturer instructions for a duration of 8 weeks.
Semen analysis All specimens will be collected by masturbation at the Andrology Laboratory after 48-72 hours of sexual abstinence. Samples will be allowed to liquefy completely for 15-20 minutes at 37C before further processing. After complete liquefaction, semen analysis will be carried out using automated LensHooke™X1 PRO semen quality analyzer (Bonraybio Co., Ltd) to determine sperm concentration and motility, progressive motility (Agarwal et al., 2019). Viability will be determined by Eosin-Nigrosin stain if motility is <25%. Smears of the raw semen will be stained with a Diff-Quik kit (Baxter Healthcare Corporation, Inc., McGaw Park, IL) for assessment of sperm morphology according to strict criteria as described in the WHO, 5th edition guideline.
White blood cell measurement When the round cell concentration in the ejaculate is >1 X million/mL or >5 round cells per high power field, the sample will be tested for leukocytospermia, i.e. >1 X million white blood cells/mL. This will be confirmed by the peroxidase or the Endtz test.
Measurement of Oxidation Reduction Potential ORP measures the transfer of electrons from a reductant (or antioxidant) to an oxidant. ORP is measured in millivolts (mV). In the current study, ORP will be measured using novel galvanostat-based technology-the MiOXSYS System (Aytu Bioscience, Englewood, CO). Briefly, 30µL of liquefied semen will be loaded on the MiOXSYS sensor. The sensor will be inserted into the MiOXSYS analyzer. Static ORP (sORP), measured in mV, is the integrated measure of the existing balance between total oxidants and reductants in a biological system. Data will be normalized with sperm concentration. ORP will be expressed as mV/ million sperm/mL.
DNA fragmentation DNA fragmentation will be assessed via Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL assay). Briefly, 2 million spermatozoa will be washed in phosphate buffered saline (PBS) and resuspended in 3.7% paraformaldehyde. A total of 2 aliquots (A and B) will be used for each donor, one for ORP measurement and other for measurement of sperm DNA fragmentation. These will be placed on ice for 30-60 minutes at 4C. Thereafter, the spermatozoa will again be washed to remove the paraformaldehyde and then re-suspended in 70% ice-cold ethanol, stored at -20C until the time of analysis.
Sperm DNA fragmentation will be evaluated using a TUNEL assay with an Apo-DirectTM kit (Pharmingen, San Diego, CA). Positive and negative kit controls provided by the manufacturer and positive test prepared by treating with hydrogen peroxide controls will be included for each run. Following a second wash in PBS to remove ethanol, the sperm pellets are re-suspended in 50 µL of freshly prepared staining solution for 60 minutes at 37C. The staining solution contains terminal deoxytransferase (TdT) enzyme, TdT reaction buffer, fluorescein isothiocynate tagged deoxyuridine triphosphate nucleotides (FITC-dUTP) and distilled water. All specimens are further washed in rinse buffer and re-suspended in 0.5 mL of propidium Iodide/RNase solution, and incubated for 30 minutes followed by flow cytometric analysis.
BD C6 Acuri cytometry analysis: All fluorescence signals of labelled spermatozoa will be analyzed by the flow cytometer BD Accuri Flow cytometer (Becton Dickinson, San Jose, CA). About 10,000 spermatozoa will be examined for each assay at a slow flow rate of <100 cells/sec. The laser excitation is provided at 2 wavelengths of 488 nm supplied by a solid blue state laser at 20mW and 640 nm powered by 14.7mW diode red laser. Green fluorescence (480-530 nm) is measured in the FL-1 channel and red fluorescence (640 nm) in the FL-2 channel. The percentage of positive cells (TUNEL-positive) will be calculated using the flow cytometer software.
Proteomic analysis Individual samples collected from each group will be subjected to 65% percoll gradient to specifically remove the white blood cells. Semen samples will be washed with PBS three times. Once the supernatant is removed, spermatozoa will be solubilized in radio-immunoprecipitation assay (RIPA) lysis buffer containing the proteinase inhibitor cocktail. After complete lysis of the spermatozoa, protein concentration will be determined using a bicinchoninic acid (BCA) kit and equal amounts of proteins will be fractionated using SDS-Page 1D gel electrophoresis. Separated bands will be cut from a single Coomassie blue stained 1D gel and analyzed. The bands will be washed, reduced, alkylated, and digested with trypsin. The digests will be separated by capillary column LC-tandem MS and the CID spectra searched against the human reference sequence database.
Functional annotation and enrichment analysis will be performed using publicly available bioinformatics annotation tools and databases such as GO Term Finder, GO Term Mapper, UniProt, Software Tools for Researching Annotations of Proteins (STRAP), Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.niaid.nih.gov), and proprietary software package such as IPA (Ingenuity Pathway Analysis) from Ingenuity® Systems, used to obtain consensus-based, comprehensive functional context for the large list of proteins derived from proteomic study. The data will be subjected to STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), a biological database and web resource of known and predicted protein-protein interactions. This will help in identifying critical proteins involved in reproductive function.
Data analysis All the data will be analyzed using the using the MedCalc Software (V. 17.8; MedCalc Software, Ostend, Belgium). Paired t-test will be used if the distribution is normal. Whereas, Wilcoxon signed rank tests will be used for parameters that do not follow normal distribution. For paired T-test comparisons based on 20 samples for each experiment, the power should be least 90% for parameters where a coefficient of variation is no more than 20%.
- Conditions
- Male Infertility
- Being tested
- new device against ambient electromagnetic radiation, sham device against ambient electromagnetic radiation
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
new device against ambient electromagnetic radiationDevice
New device provides protection against the radiations emitted by the smartphone and laptop devices. Device uses conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation.
sham device against ambient electromagnetic radiationDevice
Sham device as as a control for new device, which provides protection against the radiations emitted by the smartphone and laptop devices. Device uses conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation.
| Study group | Role | What they receive |
|---|---|---|
| Sham Qi-Shield user group | Sham comparator | Not described Receives: Device: sham device against ambient electromagnetic radiation |
| Qi-Shield user group | Active comparator | Not described Receives: Device: new device against ambient electromagnetic radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sperm concentration
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 0 weeks
Sperm concentration
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 4 weeks
Sperm concentration
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 8 weeks
Total sperm motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 0 weeks
Total sperm motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 4 weeks
Total sperm motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 8 weeks
Progressive motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 0 weeks
Progressive motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 4 weeks
Progressive motility
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 8 weeks
Sperm morphology
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 0 weeks
Sperm morphology
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 4 weeks
Sperm morphology
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Measured: 8 weeks
Seminal oxidative stress
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Measured: 0 weeks
Seminal oxidative stress
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Measured: 4 weeks
Seminal oxidative stress
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Measured: 8 weeks
Sperm DNA damage
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Measured: 0 weeks
Sperm DNA damage
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Measured: 4 weeks
Sperm DNA damage
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Measured: 8 weeks
Sperm proteome
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Measured: 0 weeks
Sperm proteome
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Measured: 4 weeks
Sperm proteome
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start14 Sep 2020
- Primary completion1 Mar 2021 (estimated)
- Study completion1 Apr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Male InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised double blind controlled study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Waveguard GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashok Agarwal, PhD, Principal investigator, American Center for Reproductive Medicine, Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04541459
- Sponsor's protocol ID
- WAVEGUARD MALE FERTILITY CC01
- Other IDs
- IRB #20-329
- Status last verified
- Oct 2020
- First submitted
- 27 Aug 2020
- Last updated
- 6 Oct 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Agarwal A, Deepinder F, Sharma RK, Ranga G, Li J. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008 Jan;89(1):124-8. doi: 10.1016/j.fertnstert.2007.01.166. Epub 2007 May 4.
PubMed 17482179Agarwal A, Desai NR, Makker K, Varghese A, Mouradi R, Sabanegh E, Sharma R. Effects of radiofrequency electromagnetic waves (RF-EMW) from cellular phones on human ejaculated semen: an in vitro pilot study. Fertil Steril. 2009 Oct;92(4):1318-1325. doi: 10.1016/j.fertnstert.2008.08.022. Epub 2008 Sep 20.
PubMed 18804757Agarwal A, Henkel R, Huang CC, Lee MS. Automation of human semen analysis using a novel artificial intelligence optical microscopic technology. Andrologia. 2019 Dec;51(11):e13440. doi: 10.1111/and.13440. Epub 2019 Oct 4.
PubMed 31583732Desai NR, Kesari KK, Agarwal A. Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system. Reprod Biol Endocrinol. 2009 Oct 22;7:114. doi: 10.1186/1477-7827-7-114.
PubMed 19849853Kesari KK, Agarwal A, Henkel R. Radiations and male fertility. Reprod Biol Endocrinol. 2018 Dec 9;16(1):118. doi: 10.1186/s12958-018-0431-1.
PubMed 30445985Kivrak EG, Yurt KK, Kaplan AA, Alkan I, Altun G. Effects of electromagnetic fields exposure on the antioxidant defense system. J Microsc Ultrastruct. 2017 Oct-Dec;5(4):167-176. doi: 10.1016/j.jmau.2017.07.003. Epub 2017 Aug 2.
PubMed 30023251
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of New Devices Against Ambient Electromagnetic Radiation: A Randomized Double Blind Controlled Study
- ClinicalTrials.gov ID
- NCT04541459
- Acronym / sponsor ID
- WAVEGUARD MALE FERTILITY CC01
- Conditions
- Male Infertility
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Waveguard GmbHIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 1 Mar 2021 (estimated)
- Study completion
- 1 Apr 2021 (estimated)
- First posted
- 9 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Project Summary Cell phones have become indispensable devices in the investigator's daily life. These phones operate between 400 and 2000 MHz frequency bands and emit radiofrequency electromagnetic waves (EMW). Radio-frequency electro-magnetic field exposure from cell phones or other sources of microwaves have deleterious effects on sperm parameters (like sperm count, morphology, motility). Further, EMW radiation emitted by mobile phones affects cells and organelles, and results in disorientation of charged molecules within the cytosol and a distortion of electron flow along the internal membranes of the cells. These cellular changes results in the generation of ROS leading to oxidative stress, which in turn results in radiation-induced sperm DNA fragmentation.
Radiation shield can help provide protection from high levels of EMW radiations deflecting, diverting, and absorbing the radiation between the user and the source. A new EMW radiation shield, Qi-Shield device developed by Waveguard GmbH (Bautzen, Germany) provides protection against the radiations emitted by the smartphone and laptop devices. Qi-Shield utilizes conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation.
Study Aims:
To evaluate the changes in the semen parameters from the use of Qi-Shield device in sham (control) and user groups To determine the molecular changes pertaining to sperm proteins from the use of Qi-Shield device in sham (control) and user groups
Significance The negative health consequences of EMWs have been documented across a wide range of device types, exposure frequencies and doses (Giuliani, 2010), at field strengths substantially below the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for permissible exposures. In the absence of a revision in the ICNIRP guidelines, near-term public exposures to EMWs will most certainly continue to increase, despite the scientific evidence suggesting more careful review and recommendations to limit exposure to electromagnetic fields as much as possible. At present, there is no veritable means for counteracting the negative health consequences of human-made EMWs, revealing an unmet need for a means of protecting from or ameliorating the negative effects of EMWs, and the need for devising strategies for creating safer living and working environments in a time of increasing EMW exposures.
Positive results in this study would demonstrate a means of counteracting negative effects on human sperm due to EMWs. Documentation of protection due to the Qi-Shield devices would show proof of principle that a low-cost passive device, portable and without battery or mains power, can provide improvements in human sperm parameters, with promise for a means of counteracting EMW-reduced fertility in large numbers of people. Confirmation of changes on protein expression would provide data needed to identify specific pathways of action, insight that is necessary for a more detailed understanding of the mechanisms of action of the EMW protection effect. Taken together, these results would suggest further lines of study in EMW protection, and provide clinical support for the adoption of EMW-protecting devices in the home and workplace.
Detailed description
Normal healthy men enrolled in the study will be asked to provide semen specimens prior to the use of device. Samples will be produced with a minimum of 48-72 hours of abstinence. Further, the subjects will be blindly assigned with either sham Qi-Shield or Qi-Shield device and will be instructed to use the device for a duration of 8 weeks .Semen samples will be provided by the subjects at 0, 4 and 8 weeks interval.
Group 1 study subjects will be provided with sham Qi-Shield device, whereas Group 2 study subjects with be provided with actual Qi-Shield device. Each user will be provided with a small carrier bag to accommodate the device during their travel. The participants are advised to keep the device within 3 meters of range as per the manufacturer instructions for a duration of 8 weeks.
Semen analysis All specimens will be collected by masturbation at the Andrology Laboratory after 48-72 hours of sexual abstinence. Samples will be allowed to liquefy completely for 15-20 minutes at 37C before further processing. After complete liquefaction, semen analysis will be carried out using automated LensHooke™X1 PRO semen quality analyzer (Bonraybio Co., Ltd) to determine sperm concentration and motility, progressive motility (Agarwal et al., 2019). Viability will be determined by Eosin-Nigrosin stain if motility is <25%. Smears of the raw semen will be stained with a Diff-Quik kit (Baxter Healthcare Corporation, Inc., McGaw Park, IL) for assessment of sperm morphology according to strict criteria as described in the WHO, 5th edition guideline.
White blood cell measurement When the round cell concentration in the ejaculate is >1 X million/mL or >5 round cells per high power field, the sample will be tested for leukocytospermia, i.e. >1 X million white blood cells/mL. This will be confirmed by the peroxidase or the Endtz test.
Measurement of Oxidation Reduction Potential ORP measures the transfer of electrons from a reductant (or antioxidant) to an oxidant. ORP is measured in millivolts (mV). In the current study, ORP will be measured using novel galvanostat-based technology-the MiOXSYS System (Aytu Bioscience, Englewood, CO). Briefly, 30µL of liquefied semen will be loaded on the MiOXSYS sensor. The sensor will be inserted into the MiOXSYS analyzer. Static ORP (sORP), measured in mV, is the integrated measure of the existing balance between total oxidants and reductants in a biological system. Data will be normalized with sperm concentration. ORP will be expressed as mV/ million sperm/mL.
DNA fragmentation DNA fragmentation will be assessed via Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL assay). Briefly, 2 million spermatozoa will be washed in phosphate buffered saline (PBS) and resuspended in 3.7% paraformaldehyde. A total of 2 aliquots (A and B) will be used for each donor, one for ORP measurement and other for measurement of sperm DNA fragmentation. These will be placed on ice for 30-60 minutes at 4C. Thereafter, the spermatozoa will again be washed to remove the paraformaldehyde and then re-suspended in 70% ice-cold ethanol, stored at -20C until the time of analysis.
Sperm DNA fragmentation will be evaluated using a TUNEL assay with an Apo-DirectTM kit (Pharmingen, San Diego, CA). Positive and negative kit controls provided by the manufacturer and positive test prepared by treating with hydrogen peroxide controls will be included for each run. Following a second wash in PBS to remove ethanol, the sperm pellets are re-suspended in 50 µL of freshly prepared staining solution for 60 minutes at 37C. The staining solution contains terminal deoxytransferase (TdT) enzyme, TdT reaction buffer, fluorescein isothiocynate tagged deoxyuridine triphosphate nucleotides (FITC-dUTP) and distilled water. All specimens are further washed in rinse buffer and re-suspended in 0.5 mL of propidium Iodide/RNase solution, and incubated for 30 minutes followed by flow cytometric analysis.
BD C6 Acuri cytometry analysis: All fluorescence signals of labelled spermatozoa will be analyzed by the flow cytometer BD Accuri Flow cytometer (Becton Dickinson, San Jose, CA). About 10,000 spermatozoa will be examined for each assay at a slow flow rate of <100 cells/sec. The laser excitation is provided at 2 wavelengths of 488 nm supplied by a solid blue state laser at 20mW and 640 nm powered by 14.7mW diode red laser. Green fluorescence (480-530 nm) is measured in the FL-1 channel and red fluorescence (640 nm) in the FL-2 channel. The percentage of positive cells (TUNEL-positive) will be calculated using the flow cytometer software.
Proteomic analysis Individual samples collected from each group will be subjected to 65% percoll gradient to specifically remove the white blood cells. Semen samples will be washed with PBS three times. Once the supernatant is removed, spermatozoa will be solubilized in radio-immunoprecipitation assay (RIPA) lysis buffer containing the proteinase inhibitor cocktail. After complete lysis of the spermatozoa, protein concentration will be determined using a bicinchoninic acid (BCA) kit and equal amounts of proteins will be fractionated using SDS-Page 1D gel electrophoresis. Separated bands will be cut from a single Coomassie blue stained 1D gel and analyzed. The bands will be washed, reduced, alkylated, and digested with trypsin. The digests will be separated by capillary column LC-tandem MS and the CID spectra searched against the human reference sequence database.
Functional annotation and enrichment analysis will be performed using publicly available bioinformatics annotation tools and databases such as GO Term Finder, GO Term Mapper, UniProt, Software Tools for Researching Annotations of Proteins (STRAP), Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.niaid.nih.gov), and proprietary software package such as IPA (Ingenuity Pathway Analysis) from Ingenuity® Systems, used to obtain consensus-based, comprehensive functional context for the large list of proteins derived from proteomic study. The data will be subjected to STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), a biological database and web resource of known and predicted protein-protein interactions. This will help in identifying critical proteins involved in reproductive function.
Data analysis All the data will be analyzed using the using the MedCalc Software (V. 17.8; MedCalc Software, Ostend, Belgium). Paired t-test will be used if the distribution is normal. Whereas, Wilcoxon signed rank tests will be used for parameters that do not follow normal distribution. For paired T-test comparisons based on 20 samples for each experiment, the power should be least 90% for parameters where a coefficient of variation is no more than 20%.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised double blind controlled study
| Arm | Type | Receives |
|---|---|---|
| Sham Qi-Shield user group | Sham comparator | Device: sham device against ambient electromagnetic radiation |
| Qi-Shield user group | Active comparator | Device: new device against ambient electromagnetic radiation |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Normal healthy men with normozoospermic semen parameters.
Key exclusion criteria (8 listed)
- Subjects with a history of smoking
- Chewing tobacco
- Alcohol consumption
- Antioxidant supplementation
- Orchitis, varicocele, tuberculosis, diabetes mellitus, and hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| new device against ambient electromagnetic radiationNew device provides protection against the radiations emitted by the smartphone and laptop devices. Device uses conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation. | Device | Qi-Shield user group |
| sham device against ambient electromagnetic radiationSham device as as a control for new device, which provides protection against the radiations emitted by the smartphone and laptop devices. Device uses conductive fluids in a particular geometric arrangement intended to ameliorate the negative effects of EMW radiation. | Device | Sham Qi-Shield user group |
Primary outcome
Sperm concentration
Time frame: 0 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Sperm concentration
Time frame: 4 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Sperm concentration
Time frame: 8 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm concentration (millions/ mL) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Total sperm motility
Time frame: 0 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Total sperm motility
Time frame: 4 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Total sperm motility
Time frame: 8 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Total motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Progressive motility
Time frame: 0 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Progressive motility
Time frame: 4 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Progressive motility
Time frame: 8 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Progressive motility (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Sperm morphology
Time frame: 0 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Sperm morphology
Time frame: 4 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Sperm morphology
Time frame: 8 weeks
Semen analysis will be carried out using LensHooke™X1 PRO semen quality analyzer. Sperm morphology (%) will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group).
Seminal oxidative stress
Time frame: 0 weeks
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Seminal oxidative stress
Time frame: 4 weeks
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Seminal oxidative stress
Time frame: 8 weeks
ORP is considered as a marker of oxidative stress. Increased levels of oxidative stress is harmful to the spermatozoa. In semen samples ORP is measured using MiOXSYS analyzers. Seminal ORP will be assessed in both the groups (Qi-shield user group and sham Qi-shield user group) to evaluate the change in the seminal oxidative stress due to use of Qi-shield.
Sperm DNA damage
Time frame: 0 weeks
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Sperm DNA damage
Time frame: 4 weeks
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Sperm DNA damage
Time frame: 8 weeks
Sperm DNA integrity is directly correlated with the quality of the spermatozoa. Increased levels of sperm DNA damage has negative impact on pregnancy and live birth rates. Sperm DNA fragmentation (SDF) is measured using TUNEL assay. In the current study levels of SDF before and after the use of Qi-shield will allow us to understand the effect of electromagnetic radiations on DNA integrity of spermatozoa.
Sperm proteome
Time frame: 0 weeks
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Sperm proteome
Time frame: 4 weeks
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Sperm proteome
Time frame: 8 weeks
In spermatozoa normal expression of fertility associated proteins are essential for fertilization process. Several studies reported that aberrant expression of proteins related to sperm function as capacitation, hyperactivation, acrosome reaction and binging of zona pellucida with ovum in infertile men. Furthermore, electromagnetic radiations can also cause molecular changes. In the present study, proteome profile of the spermatozoa from subjects before and after the use of Qi-shield will provide the information related to the molecular changes at protein level.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
- Background: PubMed 17482179Agarwal A, Deepinder F, Sharma RK, Ranga G, Li J. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008 Jan;89(1):124-8. doi: 10.1016/j.fertnstert.2007.01.166. Epub 2007 May 4.
- Background: PubMed 18804757Agarwal A, Desai NR, Makker K, Varghese A, Mouradi R, Sabanegh E, Sharma R. Effects of radiofrequency electromagnetic waves (RF-EMW) from cellular phones on human ejaculated semen: an in vitro pilot study. Fertil Steril. 2009 Oct;92(4):1318-1325. doi: 10.1016/j.fertnstert.2008.08.022. Epub 2008 Sep 20.
- Background: PubMed 31583732Agarwal A, Henkel R, Huang CC, Lee MS. Automation of human semen analysis using a novel artificial intelligence optical microscopic technology. Andrologia. 2019 Dec;51(11):e13440. doi: 10.1111/and.13440. Epub 2019 Oct 4.
- Background: PubMed 19849853Desai NR, Kesari KK, Agarwal A. Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system. Reprod Biol Endocrinol. 2009 Oct 22;7:114. doi: 10.1186/1477-7827-7-114.
- Background: PubMed 30445985Kesari KK, Agarwal A, Henkel R. Radiations and male fertility. Reprod Biol Endocrinol. 2018 Dec 9;16(1):118. doi: 10.1186/s12958-018-0431-1.
- Background: PubMed 30023251Kivrak EG, Yurt KK, Kaplan AA, Alkan I, Altun G. Effects of electromagnetic fields exposure on the antioxidant defense system. J Microsc Ultrastruct. 2017 Oct-Dec;5(4):167-176. doi: 10.1016/j.jmau.2017.07.003. Epub 2017 Aug 2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashok Agarwal, PhD principal investigator
American Center for Reproductive Medicine, Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing new device against ambient electromagnetic radiation in people with Male Infertility, run by Waveguard GmbH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ashok Agarwal, PhD (+1(216) 444-9485, agarwaa@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sperm concentration (time frame: 0 weeks). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04541459, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2020.