Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential (Androsi-Test)
Primary Purpose
Asthenozoospermia, Mitochondrial Damage
Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
ANDROSITOL®TEST
Sponsored by
About this trial
This is an interventional diagnostic trial for Asthenozoospermia focused on measuring Male infertility, Sperm parameters, Mitochondrial membrane potential
Eligibility Criteria
Inclusion Criteria:
/
Exclusion Criteria:
- Absolute asthenozoospermia
- Leukocytospermia
- Positive semen culture and/or urethral swab
- Human Papilloma Virus (HPV) DNA in semen
- History of cryptorchidism
- 3rd degree varicocele
- Markedly reduced testicular volume
- Decompensated diabetes mellitus and other systemic diseases leading to oxidative stress (e.g. chronic renal failure, liver failure)
- Altered concentrations of the following hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, prolactin, 17β-estradiol
- Alcohol and drug abuse
- Heavy cigarette smoke (≥10 cigarettes/day)
- Body Mass Index (BMI) >35 kg/m2
Sites / Locations
- Department of Clinical and Experimental Medicine, University of Catania
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ANDROSITOL®TEST
Arm Description
At least 45 patients (13 for each category: low, medium, and high responders, + 15% of hypothetical drop-outs)
Outcomes
Primary Outcome Measures
Response to the ANDROSI-TEST
Number of poor and high responders to ANDROSI-TEST
Sperm parameters
Percentage of total and progressive sperm motility and percentage of spermatozoa with high or low mitochondrial membrane potential
Secondary Outcome Measures
Other Sperm parameters (1)
Sperm concentration (mil/ml) and Sperm total count (mil/ejaculate)
Other Sperm parameters (2)
Percentage of spermatozoa with normal morphology
Effects after therapy (1)
Re-evaluation of number of poor and high responders to ANDROSI-TEST 3 months after the discontinuation of Andrositol intake
Effects after therapy (2)
Re-evaluation of percentage of total and progressive sperm motility and percentage of spermatozoa with high or low mitochondrial membrane potential 3 months after the discontinuation of Andrositol intake
Effects after therapy (3)
Re-evaluation of sperm concentration (mil/ml) and Sperm total count (mil/ejaculate) 3 months after the discontinuation of Andrositol intake
Effects after therapy (4)
Re-evaluation of Percentage of spermatozoa with normal morphology 3 months after the discontinuation of Andrositol intake
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04291495
Brief Title
Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential
Acronym
Androsi-Test
Official Title
Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential Before and After Oral Supplementation With Antioxidants and Myo-inositol
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
October 23, 2018 (Actual)
Primary Completion Date
October 31, 2020 (Actual)
Study Completion Date
October 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Catania
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Mitochondria is the cellular organelle responsible for the production of the energy necessary to fuel sperm motility. It has been demonstrated that mitochondrial efficiency is correlated to the fertilizing capacity of the spermatozoon and to the production of high quality embryos. Mitochondria efficiency is measured in the laboratory setting by evaluating the mitochondrial membrane potential.
Myo-inositol is the most represented stereoisomer of the family of inositols and is the only one physiologically concentrated within the seminal plasma. It is essential for sperm maturation and motility and its deficiency is also associated to a reduced sperm count. Myo-inositol promotes motility and allows recovering a higher number of sperm cells after swim-up, both in normospermic patients and in patients with altered seminal parameters.
Scientific studies have shown that semen samples treated in vitro with ANDROSITOL®DGN, show an improvement in mitochondrial efficiency that results in an increase in spermatozoa progressive motility. Based on the percentage increase in the progressive motility showed by the spermatozoa after incubation with ANDROSITOL®DGN (ANDROSITOL®TEST), it is possible to subdivide the semen samples into three categories: low, medium, and high responders.
The aim of the study is to evaluate whether the in vitro response of spermatozoa to ANDROSITOL®TEST correlates with the in vivo improvement of seminal parameters after oral treatment with antioxidants and myo-inositol.
Detailed Description
Mitochondria is the cellular organelle responsible for the production of the energy necessary to fuel sperm motility. It has been demonstrated that mitochondrial efficiency is correlated to the fertilizing capacity of the spermatozoon and to the production of high quality embryos. Mitochondria efficiency is measured in the laboratory setting by evaluating the mitochondrial membrane potential.
Myo-inositol is the most represented stereoisomer of the family of inositols and is the only one physiologically concentrated within the seminal plasma. It is essential for sperm maturation and motility and its deficiency is also associated to a reduced sperm count. Myo-inositol promotes motility and allows recovering a higher number of sperm cells after swim-up, both in normospermic patients and in patients with altered seminal parameters.
Scientific studies have shown that semen samples, both pathological and normal, treated in vitro with ANDROSITOL®DGN - a concentrate solution (66X) containing 133 mg/ml of myo-inositol - show an improvement in mitochondrial efficiency that results in an increase in spermatozoa progressive motility. Based on the percentage increase in the progressive motility showed by the spermatozoa after incubation with ANDROSITOL®DGN (ANDROSITOL®TEST), it is possible to subdivide the semen samples into three categories: low, medium, and high responders. High responders have worst mitochondrial function and lower fertilizing capacity, and could represent the category of patients most benefiting from supplementary oral therapy with antioxidants and myo-inositol.
The aim of our study is to evaluate whether the in vitro response of spermatozoa to ANDROSITOL®TEST correlates with the in vivo improvement of seminal parameters after oral treatment with antioxidants and myo-inositol. To do this, the investigators will enroll at least 13 patients for each category (low, medium, and high responder at ANDROSITOL®TEST) and they will re-evaluate conventional seminal parameters, mitochondrial function, and response to ANDROSITOL®TEST after three months of oral supplementation with ANDROSITOL® (dietary supplement of myo-inositol, vitamin E, L-carnitine, L-arginine, folic acid and selenium). The investigators hypothesize that, following supplementation, high-responder patients will exhibit the best improvement in seminal parameters, in particular in sperm motility. Furthermore, if the mitochondrial function is fully restored, they should respond less to the ANDROSITOL®TEST and could be reclassified as low responders.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthenozoospermia, Mitochondrial Damage
Keywords
Male infertility, Sperm parameters, Mitochondrial membrane potential
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ANDROSITOL®TEST
Arm Type
Experimental
Arm Description
At least 45 patients (13 for each category: low, medium, and high responders, + 15% of hypothetical drop-outs)
Intervention Type
Diagnostic Test
Intervention Name(s)
ANDROSITOL®TEST
Intervention Description
Sperm incubation with ANDROSITOL®DGN and evaluation of sperm motility and mithocondrial membrane potential
Primary Outcome Measure Information:
Title
Response to the ANDROSI-TEST
Description
Number of poor and high responders to ANDROSI-TEST
Time Frame
T0 and T1 (three months)
Title
Sperm parameters
Description
Percentage of total and progressive sperm motility and percentage of spermatozoa with high or low mitochondrial membrane potential
Time Frame
T0 and T1 (three months)
Secondary Outcome Measure Information:
Title
Other Sperm parameters (1)
Description
Sperm concentration (mil/ml) and Sperm total count (mil/ejaculate)
Time Frame
T0 and T1 (three months)
Title
Other Sperm parameters (2)
Description
Percentage of spermatozoa with normal morphology
Time Frame
T0 and T1 (three months)
Title
Effects after therapy (1)
Description
Re-evaluation of number of poor and high responders to ANDROSI-TEST 3 months after the discontinuation of Andrositol intake
Time Frame
T1 (three months) and T2 (six months - three months after supplementation withdrawal)
Title
Effects after therapy (2)
Description
Re-evaluation of percentage of total and progressive sperm motility and percentage of spermatozoa with high or low mitochondrial membrane potential 3 months after the discontinuation of Andrositol intake
Time Frame
T1 (three months) and T2 (six months - three months after supplementation withdrawal)
Title
Effects after therapy (3)
Description
Re-evaluation of sperm concentration (mil/ml) and Sperm total count (mil/ejaculate) 3 months after the discontinuation of Andrositol intake
Time Frame
T1 (three months) and T2 (six months - three months after supplementation withdrawal)
Title
Effects after therapy (4)
Description
Re-evaluation of Percentage of spermatozoa with normal morphology 3 months after the discontinuation of Andrositol intake
Time Frame
T1 (three months) and T2 (six months - three months after supplementation withdrawal)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
/
Exclusion Criteria:
- Absolute asthenozoospermia
Leukocytospermia
Positive semen culture and/or urethral swab
Human Papilloma Virus (HPV) DNA in semen
History of cryptorchidism
3rd degree varicocele
Markedly reduced testicular volume
Decompensated diabetes mellitus and other systemic diseases leading to oxidative stress (e.g. chronic renal failure, liver failure)
Altered concentrations of the following hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, prolactin, 17β-estradiol
Alcohol and drug abuse
Heavy cigarette smoke (≥10 cigarettes/day)
Body Mass Index (BMI) >35 kg/m2
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aldo E. Calogero, Professor
Organizational Affiliation
University of Catania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Clinical and Experimental Medicine, University of Catania
City
Catania
ZIP/Postal Code
95123
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25854593
Citation
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22656408
Citation
Condorelli RA, La Vignera S, Bellanca S, Vicari E, Calogero AE. Myoinositol: does it improve sperm mitochondrial function and sperm motility? Urology. 2012 Jun;79(6):1290-5. doi: 10.1016/j.urology.2012.03.005.
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26361940
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Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential
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