L-Citrulline and Tadalafil for Mild to Moderate Erectile Dysfunction

June 10, 2026 updated by: Hany Fathy Badawy, MD, Beni-Suef University

L-Citrulline Versus Tadalafil Versus Combination Therapy in Mild to Moderate Erectile Dysfunction: A Prospective Randomized Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

133

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
    • Beni Suweif Governorate
      • Banī Suwayf, Beni Suweif Governorate, Egypt, 02456
        • Recruiting
        • Department of Urology- Beni-Suef University Hospitals
        • Principal Investigator:
          • Hany F Badawy, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: L-Citrulline
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.
Drug: L-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.
Drug: Tadalafil Placebo
Oral placebo preparation matching tadalafil, administered for 12 weeks as part of the double-dummy study design.
Active Comparator: Tadalafil
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.
Drug: Tadalafil
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.
Drug: L-Citrulline Placebo
Oral placebo preparation matching L-citrulline, administered for 12 weeks as part of the double-dummy design
Experimental: L-Citrulline Plus Tadalafil
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.
Drug: L-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.
Drug: Tadalafil
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in International Index of Erectile Function-Erectile Function Domain Score
Time Frame: 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
Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in International Index of Erectile Function-5 Score
Time Frame: 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.
Baseline to 12 weeks
Treatment Adherence
Time Frame: 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
From treatment initiation to 12 weeks
Proportion of Participants Achieving Erection Hardness Score Grade 4
Time Frame: 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.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beni-Suef University

Investigators

  • Principal Investigator: Hany F Badawy, Faculty of medicine Beni-Suef University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2026

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 8, 2026

First Submitted That Met QC Criteria

June 8, 2026

First Posted (Actual)

June 11, 2026

Study Record Updates

Last Update Posted (Actual)

June 12, 2026

Last Update Submitted That Met QC Criteria

June 10, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMBSUREC-07062026g-Badawy

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared because the study includes sensitive individual-level sexual health data and treatment-related clinical information. Only aggregated, de-identified results will be reported in publications or presentations. Any future sharing of de-identified participant-level data would require additional approval from the Research Ethics Committee, Faculty of Medicine, Beni-Suef University.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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