Safety of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Erectile Dysfunction

Study Overview
=================
Brief Summary
-----------------
This phase I clinical trial is designed to evaluate the safety of autologous Mesenchymal Stem Cells (MSC) injected intracavernously.

Detailed Description
-----------------
Cellgram-ED is autologous bone marrow-derived mesenchymal stem cells ex vivo expanded for approximately 30 days. Ten patients (Diabetes -associated ED; 5 patients, Postprostatectomy; 5patients) will be injected Cellgram-ED directly into the intracavernous. Patient will be evaluated the safety and potential efficacy of MSC.

Official Title
-----------------
An Open, Single-center, Phase 1 Study to Evaluate Safety of Autologous Bone Marrow Derived Mesenchymal Stem Cell in Erectile Dysfunction.

Conditions
-----------------
Erectile Dysfunction

Intervention / Treatment
-----------------
* Drug: mesenchymal stem cell


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postprostatectomy Erectile Dysfunction A man aged 20 or older Who is willing to consent to participate in the study concerned with improving sexual activity after prostatectomy, the man has maintained normal sexual activity prior to prostatectomy Prior to prostatectomy PSA (prostate specific antigen) level<10 ng/mL At the time of Prostatectomy, Pathological Gleason sum ≤7 At the time of Prostatectomy, Pathological stage ≤ T2c 2 years or more postprostatectomy patients with PSA level ≤ 0.04 ng/mL without additional therapy after prostatectomy Who cannot satisfy sexual activity(more than 4 times) with proper sexual stimulation in spite of taking maximum dose of oral PDE5I(phos-phodiesterasetype-5 inhibitors) within last 8weeks. IIEF, EF(erectile function) domain score is under 17 Have a consistent partner who is willing to engage in sexual activity more than twice per month during the study. Diabetes-associated Erectile Dysfunction HbA1c is between 6.5% and 10% of man over 20 years of age with diabetes Who cannot satisfy sexual activity(more than 4 times) with proper sexual stimulation in spite of taking maximum dose of oral PDE5I within last 8weeks. IIEF, EF domain score is under 17 Who is willing to consent to participate in the study concerned with improving sexual activity Have a consistent partner who is willing to engage in sexual activity more than twice per month during the study. Exclusion Criteria: History of bone marrow disorders Serum AST/ALT > 3 X upper limit of normal or Creatinine > 1.5 X upper limit of normal History of hypersensitivity against a gentamycin Severe cardiovascular disease(angina, arrhythmia, cardiac failure, stroke), kidney failure, respiratory failure Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis test Positive for PSA or CEA or AFP (Carcinoembryonic antigen), history of cancer in the last five years (except Prostatic cancer) Uncontrolled hypertension or hypotension (systolic blood pressure > 170 or < 90 mm Hg, diastolic pressure > 100 or < 50 mm Hg) HbA1c exhibit greater than 10% Men on anticoagulant treatment Have a severe infectious disease Testosterone level is less than 200ng/dl Have a penile implant or willing to it Patients with morphological changes of the penis Patient's partner is trying to conceive during the trial period Unwilling to participate in the study Participating in other clinical trials in the past 30 days Unable to compliance with protocol Inappropriate patients to participate in the study according to the investigator

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cell<br>Patients will receive single intracavernous injection of Mesenchymal stem cell. Oral PDE5-inhibitor can take on demand. | Drug: mesenchymal stem cell<br>* Patients will receive single injection of Cellgram-ED( 30,000,000 mesenchymal stem cell) intracavernously.<br>* Other names: Cellgram-ED;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of adverse events | Analyze the laboratory, vital sign, physical exam results from baseline to end of the study for investigate adverse reactions and view safety. An SAE suggests a significant hazard, contraindication, side-effect, or precaution. With respect to human clinical experience, this includes any event that: Results in death. Is life-threatening.* Requires in-patient hospitalization or prolongation of existing hospitalization. Results in persistent or significant disability/incapacity. Is a congenital anomaly/birth defect. Other medically important condition Life-threatening in the definition of a SAE or adverse reaction refers to an event in which the patient was at risk of death at the time of event; it does not refer to an event, which hypothetically might have caused death if it were more severe. | 12month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the International Index of Erectile Function(IIEF) | Description of the average variation from the screening value in each group using the Student's preordered t-test (Wilcoxon's signed bank test). Function domain Erectile Function (Q1,2,3,4,5,15) : Min 6   Max 30 Orgasmic Function (Q9,10) : Min 2   Max 10 Sexual Desire (Q11,12) : : Min 2   Max 10 Intercourse Satisfaction (Q6,7,8): : Min 3   Max 15 Overall Satisfaction (Q13,14) : Min 2   Max 10 | month 1, 3, 6, 9 and 12 | 
| Penile Doppler Sonography, PDS | Change From Baseline in Peak systolic velocity (PSV) and End diastolic velocity (EDV), Evaluate Erection rigidity During the test. The normal maximum systolic blood flow of the cavernosal artery after injection of vasodilators is 30 cm / s or more. PDS results are obtained 5 min, 10 min, 15 min, 20 min, 25 min and 30 min after intracavernosal injection. The peak systolic velocity (PSV) is assessed as follows: >25 cm/s is considered to be normal, 20-25 cm/s is considered to be mild ED, 12-20 cm/s is considered to be moderate ED, <12 cm/s is considered to be severe arteriogenic impotence. The end diastolic velocity (EDV) is assessed as follows: 5 cm/s is considered to be a normal value, >5 cm/s is considered to indicate a veno-occlusive disorder. | month 6, 12 | 
| Change From Baseline in Sexual Encounter Profile (SEP) Question 2 | The SEP2 survey describes cumulative success rates for 30 days, 3 months, 6 months, 9 months and 12 months after cell treatment. SEP 2 Were you able to insert your penis into your partner's vagina? Yes or No SEP 3 Did your erection last long enough to have successful intercourse? Yes or No | month 1, 3, 6, 9 and 12 | 
| Global Assessment Question (GAQ) | The GAQ survey describes cumulative success rates for 30 days, 3 months, 6 months, 9 months and 12 months after cell treatment. GAQ Did Cellgram-ED improve your Erectile Function? Yes or No If so, did Cellgram-ED improve the ability to have sex? Yes or No | month 1, 3, 6, 9 and 12 |