Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06123156
Other study ID # 2019/0398/HP
Secondary ID 2020-002682-34
Status Not yet recruiting
Phase Phase 3
First received
Last updated
Start date June 2024
Est. completion date May 2028

Study information

Verified date November 2023
Source University Hospital, Rouen
Contact Valérie Bridoux
Phone 0232881347
Email valerie.bridoux@chu-rouen.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study aims to evaluate the efficacy of erectile rehabilitation with Sildenafil, in men treated with neoadjuvant proctectomy and radiotherapy for rectal cancer, in preventing long-term erectile dysfunction at 12 months post-operatively.


Description:

Colorectal cancer is the third most common cancer in men in France, after lung and prostate cancer. Proctectomy (possibly preceded by radiotherapy) is the most effective treatment for this cancer, but erectile dysfunction (ED) is a frequent complication, even when the nerves are preserved during dissection, and has a major impact on the quality of life of operated men. The cause of erectile dysfunction after rectal cancer surgery is usually neurological, due to intraoperative trauma to the autonomic nerves, while erectile dysfunction after radiotherapy is mainly vascular in origin, with damage to erectile tissue. Several risk factors for sexual dysfunction after rectal cancer surgery have been reported (age, neoadjuvant radiotherapy, type of resection, operative difficulties and complications, body image affected by protective stoma). On the other hand, surgical expertise may be a protective factor. In the physiological condition, the nitric oxide released by the pelvic nerves causes an increase in cyclic guanosine monophosphate, which in turn causes smooth muscle cells relaxation and an influx of blood into the cavernous body, triggering and maintaining the erection. Similar to prostatectomy, nerve damage can occur during proctectomy through stretching, heat, ischemia or inflammation; this nerve damage results in reduced nitric oxide production. Even in the absence of nerve damage, it has been demonstrated (in an animal model) that post-operative neurapraxia is responsible for the at least temporary disappearance of spontaneous and nocturnal erections, leading to cavernous hypoxia. This is followed by tissue changes (reduction in smooth and elastic muscle fibers in the corpora cavernosa, increase in collagen and endothelial dysfunction), which modify the hemodynamics of the carvernum body and ultimately lead to fibrosis of the erectile tissue. These changes can become permanent despite subsequent nerve recovery, and are exacerbated by neoadjuvant radiotherapy. It is therefore important not to wait passively for erectile function to be restored, as lack of oxygenation to the corpora cavernosa can lead to permanent fibrosis and dysfunction. This physiopathology is at the origin of the concept of erectile rehabilitation after prostatectomy, with the aim of maintain erections post-operatively and thus limiting fibrosis. The benefits of erectile re-education after prostatectomy were first reported in 1997, with the early use of intracavernous injections of alprostadil. Following this study, various rehabilitation strategies have been recommended. Early treatment, i.e. within the first month, is recommended to promote cavernous oxygenation and prevent fibrosis. The aims of rehabilitation are as follows : - limit fibrosis; - limit penis retraction and loss of height; - oxygenate the cavernum body; - preserve endothelial structure; - preserve smooth muscle cell structure. Various types of rehabilitation have been proposed: oral PDE-5 inhibitors, intra-cavernosal injections, urethral suppositories or vaccum. PDE-5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thus compensating for the reduction in nitric oxide and enabling a better erection. Erectile rehabilitation using PDE-5 inhibitors could protect cavernous smooth muscle from irreversible pathophysiological changes. The basic concept is to administer a PDE-5 inhibitor at bedtime to facilitate nocturnal erections, which are thought to have a natural protective effect on the function of the cavernous bodies. Padma-Nathan et al. reported the prospective administration of sildenafil 50 and 100 mg vs. placebo, daily and at bedtime, in patients undergoing nerve-sparing radical prostatectomy. After 36 weeks, erectile function was significantly better in the sildenafil group, with 27% responders, vs. 4% in the placebo group. The mechanisms involved in erectile dysfunction after proctectomy for rectal cancer are similar to those of radical prostatectomy for prostate cancer. The efficacy of PDE-5 inhibitors in the treatment of erectile dysfunction after proctectomy has already been demonstrated. However, its use as a preventive measure has rarely been reported. Three studies have evaluated PDE-5 inhibitors in patients with erectile dysfunction after rectal resection, two of which used sildenafil (Viagra, Pfizer, New York, NY) To our knowledge, only one study has evaluated the role of PDE-5 inhibitors (PDE-5i) in a preventive strategy. Originality and innovation Despite the fact that sexual dysfunction is recognized as a frequent complication of rectal cancer treatment, there are currently no recommendations for its prevention and management. In contrast to prostate cancer patients, information and treatment concerning erectile dysfunction (ED) are not systematically offered to men with colorectal cancer. The ability of sildenafil to facilitate the return of erections after radical prostatectomy has been demonstrated in several studies, and this treatment could benefit patients treated for rectal cancer. To date, no randomized study has examined the usefulness of this early rehabilitation in patients managed for rectal cancer. This study proposes, for the first time, to evaluate the use of sildenafil after neo-adjuvant radiotherapy and surgery for rectal cancer.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 188
Est. completion date May 2028
Est. primary completion date May 2028
Accepts healthy volunteers No
Gender Male
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: - Men aged 18 to 70 - Patients undergoing surgery for cancer of the lower or middle rectum by total removal of the mesorectum with colorectal or coloanal anastomosis after neoadjuvant radiotherapy, with normal preoperative erectile function (defined by a combined IIEF erectile function domain score of at least 22). - Nerve-conserving surgery - Sexually active patient without treatment for erectile function prior to surgery - Presence of a regular sexual partner (male or female) - Adult having read and understood the information letter and signed the consent form - Membership of a social security scheme Exclusion Criteria: - T4 tumor or tumor requiring extended surgery - Patients with abnormal erectile function defined by a combined IIEF erectile function domain score of less than 22. - History of prostate cancer - Sleep disorders, patients taking sedatives/hypnotics - Contraindication to SILDENAFIL EG 50 mg, film-coated tablet - Contraindication to placebo - Patients already treated with PDE5 inhibitors - Patients suffering from SARS COV 2* - Person deprived of liberty by an administrative or judicial decision or person placed under court protection / sub-guardianship or guardianship. - Any history of illness or psychological or sensory abnormality likely to prevent the subject from fully understanding the conditions required for participation in the protocol, or to prevent the subject from giving informed consent. - Person participating in another drug trial.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sildenafil
Sildénafil during 10 months (50mg daily), start 30 days after surgery
Other:
Placebo
1 platelet during 10 months (daily), start 30 days after surgery

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Rouen

Outcome

Type Measure Description Time frame Safety issue
Primary the patient's response A patient is defined as a responder by a score of at least 22 for the erectile function domain of the International Index of Erectile Function (IIEF), comprising the six IIEF questions relating to erection (Q1-Q5 and Q15). 12 months postoperatively
Secondary IIEF erectile function domain score Mesure of IIEF erectile function domain score, comprising the six IIEF erectile function questions (Q1-Q5 andQ15) at D0, M1, M3, M6, M9 and M12 Day 0, Month 1, Month 3, Month 6, Month 9, Month12
Secondary International Index of Erectile Function (IIEF) global score International Index of Erectile Function (IIEF) global score measured at D0, M1, M3, M6, M9 and M12 Day 0, Month 1, Month 3, Month 6, Month 9, Month 12
Secondary Quality of life score Mesure of quality of life score (EORTC QLQ - C30 and QLQ - CR29) at D0, M1, M3, M6, M9 and M12 Day 0, Month 1, Month 3, Month 6, Month 9, Month 12
Secondary LARS score LARS score measured at D0, M1, M3, M6, M9 and M12 Day 0, Month 1, Month 3, Month 6, Month 9, Month 12
Secondary Fecal Continence Score Fecal Continence Score (Wexner score) measured at D0, M1, M3, M6, M9 and M12 Day 0, Month 1, Month 3, Month 6, Month 9, Month 12
Secondary Spontaneous erection evaluation Number of patients with spontaneous erections on treatment at M3, M6, M9 and without treatment at M1, and M12 Month 1, Month 3, Month 6, Month 9, Month 12
Secondary Benefits of psychological follow-up The number of patients with or without regular psychological follow-up. A patient is defined as having regular follow-up if he/she visits a psychologist and/or psychiatrist once or twice a month. after 10 months of treatment
Secondary Compliance with treatment Number of unused tablets during the study. The patient will be considered as non-compliant if pill-taking over the entire 10-month treatment period is <80%. after 10 months of treatment
Secondary Adverse and suspected adverse events Number of AEs and SAEs in each group at M1, M3, M6, M9 and M12 Month 1, Month 3, Month 6, Month 9, Month 12
See also
  Status Clinical Trial Phase
Recruiting NCT06380101 - Evaluating a Nonessential Amino Acid Restriction (NEAAR) Medical Food With Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer (LARC) N/A
Active, not recruiting NCT05551052 - CRC Detection Reliable Assessment With Blood
Recruiting NCT04323722 - Impact of Bladder Depletion on Mesorectal Movements During Radiotherapy in Rectal Cancer N/A
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT04088955 - A Digimed Oncology PharmacoTherapy Registry
Active, not recruiting NCT01347697 - Collagen Implant (Biological Mesh) Versus GM Flap for Reconstruction of Pelvic Floor After ELAPE in Rectal Cancer N/A
Recruiting NCT04495088 - Preoperative FOLFOX Versus Postoperative Risk-adapted Chemotherapy in Patients With Locally Advanced Rectal Cancer Phase 3
Withdrawn NCT03007771 - Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia Phase 1
Terminated NCT01347645 - Irinotecan Plus E7820 Versus FOLFIRI in Second-Line Therapy in Patients With Locally Advanced or Metastatic Colon or Rectal Cancer Phase 1/Phase 2
Not yet recruiting NCT03520088 - PROSPECTIVE CONTROLLED AND RANDOMIZED STUDY OF THE GENITOURINARY FUNCTION AFTER RECTAL CANCER SURGERY IN RELATION TO THE DISSECTION OF THE INFERIOR MESENTERIC VESSELS N/A
Recruiting NCT05556473 - F-Tryptophan PET/CT in Human Cancers Phase 1
Recruiting NCT04749381 - The Role of TCM on ERAS of Rectal Cancer Patients Phase 2
Enrolling by invitation NCT05028192 - Mitochondria Preservation by Exercise Training: a Targeted Therapy for Cancer and Chemotherapy-induced Cachexia
Recruiting NCT03283540 - Transanal Total Mesorectal Excision for Rectal Cancer on Anal Physiology + Fecal Incontinence
Completed NCT04534309 - Behavioral Weight Loss Program for Cancer Survivors in Maryland N/A
Recruiting NCT05914766 - An Informational and Supportive Care Intervention for Patients With Locally Advanced Rectal Cancer N/A
Recruiting NCT04852653 - A Prospective Feasibility Study Evaluating Extracellular Vesicles Obtained by Liquid Biopsy for Neoadjuvant Treatment Response Assessment in Rectal Cancer
Recruiting NCT03190941 - Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients Phase 1/Phase 2
Terminated NCT02933944 - Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer Phase 1
Completed NCT02810652 - Perioperative Geriatrics Intervention for Older Cancer Patients Undergoing Surgical Resection N/A