The Outcomes of Intracavernosal Umbilical Cord Mesenchymal Stem Cells Implantation in Patients With Diabetic Erectile Dysfunction

Study Overview
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Brief Summary
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Erectile dysfunction (ED) is a complex condition affecting men worldwide. Diabetes mellitus (DM) is one of the most common causes of ED. The prevalence of ED in DM varies around 35-85%. Recently, stem cell therapy has started to become the focus of experimental and clinical studies for the treatment of ED. Stem cells have been shown to be able to regenerate functionally damaged tissue, depending on the stimuli or signals received. Stem cells studies in experimental animals have been carried out using biomarker parameters, including VEGF, Bcl-2, E-selectin, cGMP, eNOS and have been shown to be successful in increasing cell survival and angiogenesis, stimulating antiapoptotic, proneurogenic, proinflammatory, and antifibrotic effects and improvements to these biomarker parameters. This study aims to determine the efficacy, mechanism of action, and safety of umbilical cord mesenchymal stem cells as a therapy for ED due to type 2 diabetes in human.

Detailed Description
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Prior to conducting clinical trials, researchers asked for written informed consent. If the subject agrees, the study will direct the subject and control to collect basic data in the form of vital signs, blood pressure, filling out the IIEF-5 questionnaire, complete blood count (CBC), lipid profile, fasting blood glucose, HbA1c, and total testosterone, biomarker examination (E-Selectin), VEGF, Bcl-2, miRNA 16, miRNA 126), and penile Doppler ultrasound. The diagnosis of erectile dysfunction was made on the basis of an IIEF-5 score <22. Penile Doppler ultrasound was performed by a senior radiologist with interpretation of the ultrasound images performed and reported in a blinded fashion (the reader/interpreter does not know the patient's complaints). Penile Doppler ultrasound examination was performed under flaccid conditions and post-sexual stimulation conditions. Prior to the examination, the patient was given sildenafil 100 mg orally, then the flaccid phase was examined. Patients were asked to perform sexual stimulation of themselves and measurements were taken afterwards. Parallel with the patient recruitment, stem cells processing was carried out based on the production method using xeno-free material. At the baseline, patient receive intracavernous injection procedure, as a following steps: The base of the penis is clamped with ethiloop before the injection is performed. Intracavernous injection was performed in each body of 7.5 x 10^6 cells/1cc. Clamps are removed after 30 minutes post-injection to increase stem cell residency and grafting time. After the procedure, we monitor the symptoms for 1 hour to assess the presence or absence of complications before the subject can go home. We also administer PDE-5 inhibitor to all research subjects, namely tadalafil at a dose of 1 x 2.5 mg for 3 months. Follow-up was carried out on all subjects both from the experimental group and the control group by evaluating parameters consisting of IIEF-5, DPL, Lipid profile, HbA1c, GDS, total testosterone, Doppler ultrasound, e-selectin, Bcl-2, VEGF, miRNA 16, miRNA 126 at first and third month after baseline. After all data have been collected, we will perform data analysis and make research report.

Official Title
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The Outcomes of Intracavernosal Umbilical Cord Mesenchymal Stem Cells Implantation in Patients With Diabetic Erectile Dysfunction

Conditions
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Urologic Diseases, Erectile Dysfunction With Diabetes Mellitus

Intervention / Treatment
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* Biological: stem cells
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years old willing to participate as research subject patient with erectile dysfunction and Diabetes Mellitus type 2 with IIEF-5 score <22 patient has sexual partner and sexually active patient is currently not consuming PDE-5 inhibitor drugs Exclusion Criteria: patient has psychopathology and/or mental retardation patient with Peyronie's disease patient with hypogonadism patient has malignancy in urological and non urological fields patient has history of cardiovascular disease with intermediate and high risk

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>with 2cc saline/NaCl 0,9% solution once at baseline | Other: placebo<br>* using 2 cc saline/NaCl 0,9% solution<br>|
| Experimental: Stem Cell Group<br>with umbilical cord stem cells 15x10^6 cells in 2 cc saline/NaCl 0,9% solution once at baseline | Biological: stem cells<br>* Using umbilical cord stem cells 15x10^6 cells in 2 cc saline/NaCl 0,9% solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in IIEF-5 Score after stem cells injection | using IIEF-5 Questionnaire [numeric scale from 0 to 25] higher IIEF-5 Score means better erectile function | The questionnaire will be completed at baseline, 1st month, and 3rd month | 
| Changes in Peak Systolic Velocity (PSV) after stem cells injection | evaluated by penile doppler ultrasound [ numeric scale in cm/s] The normal value is 35cm/s, PSV <35cm/s means worse erectile function | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in End Diastolic Velocity after stem cells injection | evaluated by penile doppler ultrasound [ numeric scale in cm/s] The normal value is 5 cm/s, EDV >5cm/s means worse erectile function | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in Resistive Index after stem cells injection | evaluated by penile doppler ultrasound [numeric scale] The normal value is >0.9, if RI<0.75 means worse erectile function | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in Pulsatility Index after stem cells injection | evaluated by penile doppler ultrasound [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in E-selectin expression after stem cells injection | evaluated by biomolecular examination using blood sample [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in Vascular Endothelial Growth Factor (VEGF) expression after stem cells injection | evaluated by biomolecular examination using blood sample [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in Bcl-2 expression after stem cells injection | evaluated by biomolecular examination using blood sample [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in microRNA 16 expression after stem cells injection | evaluated by biomolecular examination using blood sample [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in microRNA 126 expression after stem cells injection | evaluated by biomolecular examination using blood sample [numeric scale] | The evaluation will be completed at baseline, 1st month, and 3rd month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Hba1c after stem cells injection | using blood sample [numeric scale in %] | The evaluation will be completed at baseline and 3rd month | 
| Changes in Fasting Blood Glucose after stem cells injection | using blood sample [numeric scale in mg/dL] | The evaluation will be completed at baseline and 3rd month | 
| Changes in total cholesterol after stem cells injection | using blood sample [numeric scale in mg/dL] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in low-density lipoprotein (LDL) after stem cells injection | using blood sample [numeric scale in mg/dL] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in high-density lipoprotein (HDL) after stem cells injection | using blood sample [numeric scale in mg/dL] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Changes in Triglycerides (TG) level after stem cells injection | using blood sample [numeric scale in mg/dL] | The evaluation will be completed at baseline, 1st month, and 3rd month | 
| Number of participants with side effects after intracavernosal injection | To evaluate the number of participants with side effects including: pain, swelling, bleeding, hypesthesia, and voiding difficulty after the injection. | The evaluation will be completed at baseline after the injection |