Safety and Efficiacy of Mesenchymal Stem Cell and Exosome Therapy for Diabetic Erectile Dysfunction: A Randomized Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change in Erectile Function as Measured by the International Index of Erectile Function-5 (IIEF-5) Score
研究概览
简要总结
The goal of this prospective randomized controlled clinical study is to evaluate the effectiveness and safety of intracavernosal injections of umbilical cord-derived mesenchymal stem cells (MSCs) and umbilical cord-derived MSC-derived exosomes in men aged 25 to 75 years with diabetic erectile dysfunction (ED) who have not responded adequately to conventional medical treatments such as phosphodiesterase type-5 (PDE-5) inhibitors.
Diabetes mellitus is a major risk factor for erectile dysfunction and is associated with endothelial dysfunction, impaired smooth muscle relaxation, neuropathy, and increased fibrosis within penile tissue. Although many patients respond to standard pharmacological treatments, diabetic patients often demonstrate reduced responsiveness to these therapies. Regenerative medicine approaches, including stem cell therapy and stem cell-derived exosomes, have emerged as potential therapeutic strategies due to their regenerative, angiogenic, neuroprotective, and anti-fibrotic effects.
The main questions this study aims to answer are:
- Whether intracavernosal administration of mesenchymal stem cells or MSC-derived exosomes improves erectile function, as measured by changes in the International Index of Erectile Function-5 (IIEF-5) and Erectile Hardness Score (EHS).
- Whether penile hemodynamics improve following treatment, as assessed by penile Doppler ultrasonography parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI).
Participants will be randomly assigned to one of three groups:
- Intracavernosal placebo injection
- Intracavernosal injection of umbilical cord-derived mesenchymal stem cells (5×10⁶ cells)
- Intracavernosal injection of umbilical cord-derived mesenchymal stem cell-derived exosomes (75 μg) All interventions will be administered as a single intracavernosal injection under controlled clinical conditions.
Participants will undergo baseline evaluation including medical history, physical examination, erectile function assessment using the IIEF-5 questionnaire, and penile Doppler ultrasonography. Follow-up evaluations will be conducted at 1, 3, 6, and 12 months after treatment to assess changes in erectile function, penile vascular parameters, and treatment-related adverse events.
The study will also monitor potential side effects such as pain, bruising, hematoma, edema, or other complications related to the intracavernosal injection procedure.
Participants will be recruited from patients presenting to the urology outpatient clinic with diabetic erectile dysfunction. Eligible participants must have a diagnosis of erectile dysfunction for at least six months, a history of diabetes mellitus for at least five years, and insufficient response to standard medical therapy. Patients with penile anatomical deformities, active infections, malignancy, unstable cardiovascular disease, autoimmune disease, or other contraindications to intracavernosal treatment will be excluded.
详细描述
Detailed Description This prospective randomized controlled clinical study is designed to evaluate the safety and efficacy of intracavernosal injections of umbilical cord-derived mesenchymal stem cells (MSCs) and MSC-derived exosomes in men with diabetic erectile dysfunction (ED) who have not responded adequately to conventional medical treatments such as phosphodiesterase type-5 (PDE-5) inhibitors. The study will compare these regenerative therapies with placebo in order to determine their therapeutic effectiveness.
The primary focus of the study will be the improvement in erectile function as assessed by changes in the International Index of Erectile Function-5 (IIEF-5) and Erectile Hardness Score (EHS). In addition, penile hemodynamics will be evaluated using penile Doppler ultrasonography parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI). Safety outcomes and treatment-related adverse events will also be closely monitored throughout the study period.
________________________________________ Background and Rationale Erectile dysfunction is a common condition that significantly affects quality of life in men and their partners. Diabetes mellitus is one of the most important risk factors for erectile dysfunction and is associated with endothelial dysfunction, neuropathy, reduced smooth muscle content, oxidative stress, and cavernosal fibrosis. These pathophysiological changes impair penile vascular and neural mechanisms necessary for normal erectile function.
Although phosphodiesterase type-5 inhibitors are considered first-line therapy for erectile dysfunction, patients with diabetes often demonstrate reduced responsiveness to these medications. As a result, alternative therapeutic approaches are needed for patients with treatment-resistant diabetic erectile dysfunction.
Regenerative medicine has emerged as a promising field for the treatment of erectile dysfunction. Mesenchymal stem cells have been shown in preclinical studies to promote angiogenesis, improve endothelial function, enhance neuronal regeneration, and reduce fibrosis within penile tissue. In addition to stem cells themselves, stem cell-derived exosomes have gained increasing attention as a cell-free regenerative therapy. Exosomes contain various bioactive molecules including proteins, microRNAs, and signaling factors that can stimulate tissue repair and cellular communication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients aged 25 to 75 years
- •Diagnosis of erectile dysfunction for at least 6 months
- •Type 1 or Type 2 diabetes mellitus for at least 5 years
- •Inadequate response to medical treatment, including phosphodiesterase type-5 (PDE-5) inhibitors and/or intracavernosal prostaglandin E1 therapy
- •Candidates for penile prosthesis implantation due to treatment-resistant erectile dysfunction
- •Ability and willingness to provide written informed consent
排除标准
- •Penile anatomical deformities
- •Active infection or skin lesion on the penis
- •Bleeding disorders or coagulation abnormalities
- •Previous penile prosthesis implantation, penile vascular surgery, or pelvic surgery
- •Untreated hypogonadism
- •Unstable cardiovascular disease
- •History of malignancy
- •Autoimmune disease
- •Use of immunosuppressive therapy
- •Presence of systemic or local infection
- •Uncontrolled diabetes mellitus
研究组 & 干预措施
Mesenchymal Stem Cell Treatment Group
Participants in this group will receive a single intracavernosal injection of umbilical cord-derived mesenchymal stem cells (5×10⁶ cells). The stem cells are produced under Good Manufacturing Practice (GMP) conditions and administered directly into the corpus cavernosum. The treatment aims to improve erectile function by promoting angiogenesis, tissue regeneration, and improved penile vascular function. Participants will be followed for safety and efficacy outcomes during scheduled follow-up visits.
干预措施: Umbilical Cord-Derived Mesenchymal Stem Cells (Biological)
Exosome Treatment Group
Participants in this group will receive a single intracavernosal injection of umbilical cord-derived mesenchymal stem cell-derived exosomes (75 μg). Exosomes are extracellular vesicles that contain growth factors and signaling molecules that may promote tissue repair and vascular regeneration. This cell-free regenerative therapy aims to improve erectile function in patients with diabetic erectile dysfunction.
干预措施: Umblical Cord-Derived Mesenchymal Stem Cell-Derived Exosomes (Biological)
Placebo Control Group
Participants in this group will receive a single intracavernosal injection of sterile normal saline (0.9% sodium chloride solution) as placebo. The placebo injection will be administered using the same procedure as the treatment groups in order to maintain study blinding. Participants will undergo the same follow-up assessments as the other study groups.
干预措施: Placebo Intracavernosal Injection (Biological)
结局指标
主要结局
Change in Erectile Function as Measured by the International Index of Erectile Function-5 (IIEF-5) Score
时间窗: Baseline, 1 month, 3 months, 6 months, and 12 months
The primary outcome measure is the change in erectile function assessed by the International Index of Erectile Function-5 (IIEF-5). The IIEF-5 is a validated questionnaire widely used to evaluate erectile function in men with erectile dysfunction. The score ranges from 5 to 25, with higher scores indicating better erectile function. Participants will complete the questionnaire at baseline and during follow-up visits. The study aims to determine whether intracavernosal injection of mesenchymal stem cells or mesenchymal stem cell-derived exosomes improves erectile function compared with placebo.
Change in Erectile Hardness Score (EHS)
时间窗: Baseline, 1 month, 3 months, 6 months, and 12 months
Erectile rigidity will be evaluated using the Erectile Hardness Score (EHS). EHS is a validated single-item scale ranging from 0 to 4, where higher scores indicate greater erectile rigidity. Changes in EHS from baseline will be analyzed to assess improvement in erectile function following treatment.
次要结局
- Peak Systolic Velocity (PSV) as Measured by Penile Doppler Ultrasonography(Baseline, 3 months, and 12 months)
- End-Diastolic Velocity (EDV) as Measured by Penile Doppler Ultrasonography(Baseline, 3 months, and 12 months)
- Resistive Index (RI) as Measured by Penile Doppler Ultrasonography(Baseline, 3 months, and 12 months)
研究者
Samet Şenel
Associate Professor of Urology
Ankara City Hospital Bilkent