Endothelial Markers and Tadalafil Response

Al-Azhar University120 enrolled

Overview

This prospective cohort study will recruit eligible men attending the Urology/Andrology outpatient clinic. Baseline assessment will include demographic and clinical data, cardiovascular risk assessment, erectile-function questionnaires, routine laboratory investigations, brachial artery flow-mediated dilatation, carotid intima-media thickness, and selected circulating endothelial biomarkers including endothelin-1, nitrite/nitrate, high-sensitivity C-reactive protein, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1. All participants will receive tadalafil 5 mg once daily for 12 weeks. Erectile function, adherence, and adverse events will be assessed during follow-up. The primary outcome will be clinical response at 12 weeks, defined as an improvement of at least 4 points in the IIEF-EF domain together with a positive response to the Global Assessment Question.

Erectile dysfunction is a common male sexual disorder and is often associated with endothelial dysfunction, impaired nitric oxide bioavailability, inflammation, arterial stiffness, and subclinical atherosclerosis. Because penile arteries are relatively small, vasculogenic erectile dysfunction may appear before overt cardiovascular disease. Brachial artery flow-mediated dilatation reflects endothelial-dependent vasodilation, carotid intima-media thickness reflects structural vascular change, and circulating endothelial biomarkers may provide additional information about endothelial injury and inflammation. This prospective observational cohort study will recruit men with predominantly vasculogenic erectile dysfunction attending the Urology/Andrology outpatient clinic. Baseline demographic, clinical, sexual, laboratory, vascular, and biomarker data will be collected before treatment. All participants will receive tadalafil 5 mg once daily for 12 weeks. Erectile function will be measured again at follow-up using the IIEF-EF domain, IIEF-5/SHIM, and the Global Assessment Question. The primary outcome is clinical response at 12 weeks, defined as an improvement of at least 4 points in IIEF-EF together with a positive Global Assessment Question response. The study will also evaluate whether baseline endothelial dysfunction markers improve prediction of tadalafil response beyond standard clinical variables.

Study Type

OBSERVATIONAL

Enrollment

120

Eligibility

Sex: MALEMin age: 30 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must fulfill all of the following: * Men aged 30 to 70 years. * ED lasting at least 3 months. * IIEF-5/SHIM score of 21 or less or clinically documented ED. * Clinical features suggesting predominantly vasculogenic ED. * Sexually active or willing to attempt sexual intercourse during the study. * Able to complete the study questionnaires. * Willing to take tadalafil 5 mg once daily for 12 weeks. * Able to provide written informed consent. * Willing to avoid other ED treatments during the study unless medically necessary. Exclusion Criteria: * Patients will be excluded if they have: * ED primarily attributed to psychogenic causes. * Predominantly neurogenic ED. * Severe untreated hypogonadism likely to be the primary cause of ED. * Untreated hyperprolactinemia or another major endocrine disorder. * Significant penile anatomical abnormality interfering with intercourse, including severe Peyronie's disease. * Previous radical pelvic surgery or pelvic radiotherapy. * Active urinary or genital infection. * Unstable angina or unstable cardiovascular disease. * Recent myocardial infarction or stroke. * Uncontrolled hypertension or clinically significant hypotension. * Severe renal impairment requiring an alternative tadalafil regimen. * Severe hepatic impairment. * Active malignancy or expected survival of less than one year. * Major psychiatric illness, cognitive impairment or inability to comply with follow-up. * Current use of another PDE5 inhibitor or intracavernosal therapy that cannot be discontinued. * Concomitant use of organic nitrates, nitric oxide donors or nicorandil. * Known hypersensitivity to tadalafil. * Participation in another study that may affect erectile function or vascular measurements. * Refusal or inability to provide informed consent.

Outcomes

Primary Outcomes

Clinical response to tadalafil at 12 weeks

Proportion of participants achieving clinical response, defined as an increase of at least 4 points in the IIEF-EF domain score from baseline together with a positive response to the Global Assessment Question. The IIEF-EF domain scores erectile function on a higher-is-better scale; higher scores indicate better erectile function.

Time frame: 12 weeks

Secondary Outcomes

Change in the International Index of Erectile Function erectile function score.

Change from baseline in the erectile function domain of the International Index of Erectile Function (IIEF-EF). The IIEF-EF domain is a validated erectile function score, with higher values indicating better erectile function.

Time frame: Baseline to 12 weeks

Change in Erection Hardness Score

Change from baseline in the Erection Hardness Score, a 4-point scale used to assess penile rigidity during erection. Higher scores indicate firmer erections.

Time frame: Baseline and12 weeks.

Brachial artery flow-mediated dilatation

Association between baseline brachial artery flow-mediated dilatation percentage and clinical response to tadalafil. Flow-mediated dilatation is a functional ultrasound-based measure of endothelial-dependent vasodilation; lower values indicate worse endothelial function. Baseline FMD will be evaluated as an independent predictor of treatment response.

Time frame: Baseline

Carotid intima-media thickness

Association between baseline mean carotid intima-media thickness and clinical response to tadalafil. Carotid intima-media thickness is a structural ultrasound marker of subclinical atherosclerosis; higher values indicate more advanced vascular wall thickening. Baseline CIMT will be evaluated as an independent predictor of treatment response.

Time frame: Baseline

Serum endothelin-1 level

Baseline biomarker levels will be evaluated as independent predictors of treatment response.

Time frame: Baseline

Serum nitrite/nitrate level

Baseline biomarker levels will be evaluated as independent predictors of treatment response.

Time frame: Baseline

Serum high-sensitivity C-reactive protein

Baseline biomarker levels will be evaluated as independent predictors of treatment response.

Time frame: Baseline

Adverse events during tadalafil treatment

Number and type of treatment-emergent adverse events occurring during 12 weeks of tadalafil 5 mg once-daily therapy.

Time frame: Throughout the 12-week treatment period.

Endothelial Markers and Tadalafil Response

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts