Erectile Dysfunction
Conditions
Keywords
L-citrulline, Tadalafil, International Index of Erectile Function
Brief summary
Erectile dysfunction is a common male sexual health problem that may affect quality of life and sexual relationships. Tadalafil 5 mg once daily is an established oral treatment for erectile dysfunction. L-citrulline is an oral nitric oxide pathway supplement that may improve erectile function by increasing L-arginine availability. This randomized trial will compare three oral treatment regimens in men with mild to moderate erectile dysfunction: L-citrulline 1500 mg/day, tadalafil 5 mg/day, and the combination of L-citrulline 1500 mg/day plus tadalafil 5 mg/day. Participants will receive treatment for 12 weeks and will be followed at baseline, week 4, week 8, and week 12. The primary outcome will be the change in the International Index of Erectile Function-Erectile Function domain score from baseline to 12 weeks. Secondary outcomes will include changes in IIEF-5/SHIM score, Erection Hardness Score, SEP diary outcomes, treatment adherence, adverse events, and treatment discontinuation.
Detailed description
This is a prospective, randomized, three-arm, parallel-group, active-controlled clinical trial conducted at the Urology outpatient clinics of the Department of Urology, Faculty of Medicine, Beni-Suef University, Egypt. Adult men with mild to moderate erectile dysfunction will be enrolled after written informed consent. Eligible participants will be randomized in a 1:1:1 ratio to receive one of three oral treatment regimens for 12 weeks: L-citrulline 1500 mg/day, tadalafil 5 mg/day, or combination therapy with L-citrulline 1500 mg/day plus tadalafil 5 mg/day. The preferred design is double-blind and double-dummy, using active and matching placebo preparations when available. Participants will be assessed at baseline, week 4, week 8, and week 12. Baseline assessment will include medical and sexual history, review of comorbidities and medications, physical examination, relevant laboratory tests, and validated erectile function questionnaires. The primary endpoint is change in the International Index of Erectile Function-Erectile Function domain score from baseline to 12 weeks. Secondary endpoints include change in IIEF-5/SHIM score, change in Erection Hardness Score, proportion of patients achieving Erection Hardness Score grade 4, change in affirmative SEP-3 responses, adherence, treatment-emergent adverse events, and discontinuation due to adverse events.
Interventions
DRUGL-Citrulline
Oral L-citrulline 1500 mg/day administered for 12 weeks as an active oral nitric oxide pathway supplement for men with mild to moderate erectile dysfunction.
DRUGTadalafil
Oral tadalafil 5 mg once daily administered for 12 weeks as active phosphodiesterase type 5 inhibitor therapy for men with mild to moderate erectile dysfunction.
Oral placebo preparation matching L-citrulline, administered for 12 weeks as part of the double-dummy design
Oral placebo preparation matching tadalafil, administered for 12 weeks as part of the double-dummy study design.
Sponsors
Beni-Suef University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study will use a double-blind, double-dummy design when matching placebo preparations are available. Participants, care providers, investigators, and outcome assessors will be masked to treatment allocation. Active and placebo preparations of L-citrulline and tadalafil will be dispensed in coded treatment packs according to the randomization sequence.
Intervention model description
Participants will be randomized in a 1:1:1 ratio to one of three parallel treatment arms: L-citrulline 1500 mg/day, tadalafil 5 mg/day, or combination therapy with L-citrulline 1500 mg/day plus tadalafil 5 mg/day. Each participant will receive the allocated oral treatment for 12 weeks, with follow-up visits at baseline, week 4, week 8, and week 12.
Eligibility
Sex/Gender
MALE
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male patients aged 30 to 70 years. * Erectile dysfunction for at least 3 months. * Mild to moderate erectile dysfunction, defined by International Index of Erectile Function-Erectile Function domain score from 11 to 25. * Stable sexual relationship during the study period. * Willingness to attempt sexual activity during the study period. * Ability to complete study questionnaires and attend follow-up visits. * Written informed consent.
Exclusion criteria
* Severe erectile dysfunction, defined by International Index of Erectile Function-Erectile Function domain score of 10 or less. * Current nitrate or nicorandil use. * Contraindication or hypersensitivity to tadalafil or L-citrulline. * Unstable cardiovascular disease, unstable angina, recent myocardial infarction or stroke, uncontrolled hypertension, or high-risk arrhythmia. * Severe hepatic impairment. * Severe renal impairment. * Untreated hypogonadism requiring hormonal treatment. * Hyperprolactinemia or uncontrolled endocrine disorder. * Major neurogenic erectile dysfunction, spinal cord injury, or previous radical pelvic surgery causing severe erectile dysfunction. * Significant Peyronie's disease preventing intercourse. * Active major psychiatric illness impairing reliable assessment. * Use of phosphodiesterase type 5 inhibitors, intracavernosal injection therapy, vacuum device therapy, testosterone therapy, L-arginine, L-citrulline, or erectile dysfunction nutraceuticals during the washout period before randomization. * Participation in another clinical trial during the previous 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in International Index of Erectile Function-Erectile Function Domain Score | Baseline to 12 weeks | Change in the International Index of Erectile Function-Erectile Function domain score from baseline to week 12. The Erectile Function domain score ranges from 1 to 30, with higher scores indicating better erectile function. A greater positive change indicates greater improvement in erectile function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in International Index of Erectile Function-5 Score | Baseline to 12 weeks | Change in the International Index of Erectile Function-5 score, also known as the Sexual Health Inventory for Men score, from baseline to week 12. The score ranges from 5 to 25, with higher scores indicating better erectile function. A greater positive change indicates greater improvement. |
| Treatment Adherence | From treatment initiation to 12 weeks | Percentage of prescribed study medication doses taken during the 12-week treatment period, assessed by patient report and treatment accountability at follow-up visits. Higher percentages indicate better adherence |
| Proportion of Participants Achieving Erection Hardness Score Grade 4 | 12 weeks | Percentage of participants achieving Erection Hardness Score grade 4 at week 12. Grade 4 indicates that the penis is completely hard and fully rigid. |
Countries
Egypt
Contacts
CONTACTHany F Badawy, MD
PRINCIPAL_INVESTIGATORHany F Badawy
Faculty of medicine Beni-Suef University
Outcome results
None listed