L-Citrulline and Tadalafil for Mild to Moderate Erectile Dysfunction
L-Citrulline Versus Tadalafil Versus Combination Therapy in Mild to Moderate Erectile Dysfunction: A Prospective Randomized Trial
Beni-Suef University
133 participants
Jun 8, 2026
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria7
- 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 Criteria13
- 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.
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Interventions
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.
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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07642505