L-Citrulline and Tadalafil for Mild to Moderate Erectile Dysfunction

Beni-Suef University

Status and phase: Enrolling; Phase 4

Conditions: Erectile Dysfunction

Treatments: Drug: L-Citrulline; Drug: Tadalafil; Drug: Tadalafil Placebo; Drug: L-Citrulline Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07642505

FMBSUREC-07062026g-Badawy

Details and patient eligibility

About

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.

Full 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.

Enrollment: 133 estimated patients

Sex: Male

Ages: 30 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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133 participants in 3 patient groups

L-Citrulline

Experimental group

Description:

Participants assigned to this arm will receive oral L-citrulline 1500 mg/day for 12 weeks. In the double-dummy design, participants will receive active L-citrulline plus tadalafil placebo.

Treatment:

Drug: Tadalafil Placebo

Drug: L-Citrulline

Tadalafil

Active Comparator group

Description:

Participants assigned to this arm will receive oral tadalafil 5 mg once daily for 12 weeks. In the double-dummy design, participants will receive active tadalafil plus L-citrulline placebo.

Treatment:

Drug: L-Citrulline Placebo

Drug: Tadalafil

L-Citrulline Plus Tadalafil

Experimental group

Description:

Participants assigned to this arm will receive combination oral therapy with L-citrulline 1500 mg/day plus tadalafil 5 mg once daily for 12 weeks.

Treatment:

Drug: Tadalafil

Drug: L-Citrulline