Ignite Creation Date:
2024-10-26 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 3:36 PM
Study NCT ID:
NCT06520839
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-22
Brief Title:
Genetic Factors of Erectile Dysfunction Degree and Response to Tadalafil Treatment in Patients With Diabetes
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Genetic Factors of Erectile Dysfunction Degree and Response to Tadalafil Treatment in Patients With Diabetes
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EDGEN
Brief Summary:
The goal of this clinical trial is to examine the genetic markers of erectile dysfunction degree in patients with diabetes and find new predictive models based on genetic factors with which we will be able to more accurately address the adequacy of treatment in patients with diabetes and thus have a long-term impact to reduce side effects of treatment We will look for a predictive model based on genetic analysis to determine in the future patients with a good response to treatment with phosphodiesterase type 5 inhibitors in our case tadalafil 5 mg daily The main questions it aims to answer are
1 Genetic alterations in the NO signaling pathway affect the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
2 Genetic alterations in the folate pathway affect the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
3 Genetic factors of the vascular wall influence the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
4 Genetic changes in the pathways of tadalafil metabolism and action influence the response to the treatment of erectile dysfunction in patients with diabetes
Participants will take the drug tadalafil 5 mg every day for three months The level of erectile dysfunction will be assessed with the IIEF-5 questionnaire at the beginning of the study and after three months of taking the drug
1 Genetic alterations in the NO signaling pathway affect the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
2 Genetic alterations in the folate pathway affect the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
3 Genetic factors of the vascular wall influence the degree of erectile dysfunction and the response to tadalafil treatment in patients with diabetes
4 Genetic changes in the pathways of tadalafil metabolism and action influence the response to the treatment of erectile dysfunction in patients with diabetes
Participants will take the drug tadalafil 5 mg every day for three months The level of erectile dysfunction will be assessed with the IIEF-5 questionnaire at the beginning of the study and after three months of taking the drug
Detailed Description:
We will include in the study 90 patients with diabetes and erectile dysfunction We will use the IIEF-5 questionnaire to confirm the diagnosis of erectile dysfunction Patients between the ages of 40 and 65 who score 21 points or less on the IIEF-5 scale will be included in the study
The research will be clinically pharmacological prospective interventional and genetic-associative Patients will be selected sequentially according to their willingness to participate in the research taking into account the inclusion and exclusion criteria As a result they will not be subject to randomization At the first examination and after signing the informed consent form for participation in the research blood will be taken from the patients for laboratory and molecular genetic tests they will receive the drug for the treatment of erectile dysfunction tadalafil which they will receive in a dose of 5 mg daily for a period of three months After three months patients will complete the IIEF-5 questionnaire again
At the beginning of the research we will explain the course and purpose of the research to the people involved they will fill out a consent form for participating in the research Upon inclusion we will perform the following on all subjects
History and clinical examination including weight height and body mass index The degree of erectile dysfunction will be classified using the IIEF-5 questionnaire into four categories namely severe 5-7 points moderate 8-11 points mild to moderate 12-16 points and mild form 17-21 points of erectile dysfunction
Laboratory tests Peripheral venous blood will be taken to determine laboratory parameters renal function hepatogram lipidogram HbA1c TIR PSA TSH LH FSH PRL SHBG testosterone total and free folic acid
Molecular genetic tests 3-5 ml of peripheral venous blood will be taken from the examinees in a test tube with EDTA Centrifugation will separate the blood plasma from the cellular part of the blood Genomic DNA will be isolated from the cellular part of the blood using commercial reagent sets DNA Mini Kit and Flexigene DNA kit Qiagen Hilden Germany To determine polymorphisms of individual nucleotides in the genes of the synthesis pathway NO function and folate pathway we will use modern high-throughput methods based on the real-time PCR reaction such as the 5-exonuclease test TaqMan SNP genotyping assay Applied Biosystems Foster City CA USA and allele-specific competitive PCR reactions KASPar assay KBiosciences Herts UK
Candidate genes were selected based on a literature review focusing on pathways related to the molecular pathogenesis of erectile dysfunction and pathways related to the metabolism and action of tadalafil Based on a review of the databases dbSNP PharmGKB and the literature we searched for genetic changes in the mentioned genes that are common in the white race and affect the expression of the gene or the function of the written protein Based on this we decided to include the following genes and polymorphisms in the analysis
signaling pathway NO NOS3 894GT rs1799983 786TC rs2070744
vascular wall factors VEGF 460TC rs833061 1154GA rs1570360 2578AC rs699947 ACE rs1800764 rs4343 rs1799752 ACE2 rs2285666 rs1978124
folate pathway MTHFR rs1801133 pAla222Val c 677 CT rs1801131 pGlu429Ala c1298 AC MS rs1805087 pAsp919Gly c2756AG MTRR rs1801394 pAla66Gly 66AG
tadalafil metabolism CYP3A422 and CYP3A53
tadalafil target PDE5A rs12646525 rs3806808
The research will be clinically pharmacological prospective interventional and genetic-associative Patients will be selected sequentially according to their willingness to participate in the research taking into account the inclusion and exclusion criteria As a result they will not be subject to randomization At the first examination and after signing the informed consent form for participation in the research blood will be taken from the patients for laboratory and molecular genetic tests they will receive the drug for the treatment of erectile dysfunction tadalafil which they will receive in a dose of 5 mg daily for a period of three months After three months patients will complete the IIEF-5 questionnaire again
At the beginning of the research we will explain the course and purpose of the research to the people involved they will fill out a consent form for participating in the research Upon inclusion we will perform the following on all subjects
History and clinical examination including weight height and body mass index The degree of erectile dysfunction will be classified using the IIEF-5 questionnaire into four categories namely severe 5-7 points moderate 8-11 points mild to moderate 12-16 points and mild form 17-21 points of erectile dysfunction
Laboratory tests Peripheral venous blood will be taken to determine laboratory parameters renal function hepatogram lipidogram HbA1c TIR PSA TSH LH FSH PRL SHBG testosterone total and free folic acid
Molecular genetic tests 3-5 ml of peripheral venous blood will be taken from the examinees in a test tube with EDTA Centrifugation will separate the blood plasma from the cellular part of the blood Genomic DNA will be isolated from the cellular part of the blood using commercial reagent sets DNA Mini Kit and Flexigene DNA kit Qiagen Hilden Germany To determine polymorphisms of individual nucleotides in the genes of the synthesis pathway NO function and folate pathway we will use modern high-throughput methods based on the real-time PCR reaction such as the 5-exonuclease test TaqMan SNP genotyping assay Applied Biosystems Foster City CA USA and allele-specific competitive PCR reactions KASPar assay KBiosciences Herts UK
Candidate genes were selected based on a literature review focusing on pathways related to the molecular pathogenesis of erectile dysfunction and pathways related to the metabolism and action of tadalafil Based on a review of the databases dbSNP PharmGKB and the literature we searched for genetic changes in the mentioned genes that are common in the white race and affect the expression of the gene or the function of the written protein Based on this we decided to include the following genes and polymorphisms in the analysis
signaling pathway NO NOS3 894GT rs1799983 786TC rs2070744
vascular wall factors VEGF 460TC rs833061 1154GA rs1570360 2578AC rs699947 ACE rs1800764 rs4343 rs1799752 ACE2 rs2285666 rs1978124
folate pathway MTHFR rs1801133 pAla222Val c 677 CT rs1801131 pGlu429Ala c1298 AC MS rs1805087 pAsp919Gly c2756AG MTRR rs1801394 pAla66Gly 66AG
tadalafil metabolism CYP3A422 and CYP3A53
tadalafil target PDE5A rs12646525 rs3806808
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None