Safety and Efficacy of Autologous Platelet-Rich Plasma for Erectile Dysfunction.

• ClinicalTrials.gov Identifier: NCT04396795
• Recruitment Status: Recruiting
• First Posted: May 21, 2020
• Last Update Posted: September 18, 2020
• Sponsor: University of Miami
• Information provided by (Responsible Party): Ranjith Ramasamy, MD, University of Miami

Study Description

Brief Summary:

The purpose of this study is to evaluate changes in vascular parameters and International Index of Erectile Function (IIEF) scores with the administration of Platelet Rich Plasma (PRP) to participants with Erectile Dysfunction (ED)

Condition or disease	Intervention/treatment	Phase
Erectile Dysfunction	Drug: Autologous Platelet Rich Plasma; Other: Saline solution	Phase 2

Detailed Description:

Platelet-derived therapies are a growing trend across multiple medical and surgical specialties, mainly orthopedics for conditions such as bone and soft tissue trauma, inflammatory conditions, and chronic pain syndromes. One of the most well described platelet-based therapies is autologous platelet-rich plasma (PRP). This concentrate is then administered via injection. When platelets are activated, they release these growth differentiation factors, facilitating even nerve repair and regeneration. Growth factors act locally and are implicated in many aspects of natural wound healing, including chemotaxis, cell proliferation, cell differentiation and angiogenesis.The key role of platelets in these processes makes them an attractive candidate for therapies aimed at accelerating natural healing, as well as tissue regeneration.

Although most of the studies focusing on PRP injections have been relatively small and heterogenous, they largely support the concept of administration in terms of safety, while efficacy remains uncertain.

When platelets are activated, they release many kinds of growth differentiation factors and a few types have been found to facilitate nerve repair and regeneration. Moreover, corporeal dysfunction in ED due to smooth muscle atrophy or other intra-cavernosal pathology can lead to corporo-venous occlusive erectile dysfunction despite a normal arterial inflow. Rejuvenating the Corporeal tissues with PRP, which is well known for its growth and healing factors, is a possible modality as a potential treatment for erectile dysfunction according to Alkhayal et al. In their retrospective study examining the efficacy of one intra-cavernosal PRP injection to 40 ED patients, they reported that mean IIEF-5 score before treatment was 13 (5-20) and post treatment IIEF-5 = 17 (7-24), (p < 0.001).

To date, there are no treatments that address the underlying cause of endothelial dysfunction, although LIST treatment for ED has shown promising results. Platelet-derived therapies targeting inflammation and promoting tissue/nerve regeneration and may represent a potential treatment option towards this direction.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Control, Double-Blind, Placebo Controlled, Multicenter Clinical Trial on Safety and Efficacy of Autologous Platelet-Rich Plasma Injection Treatment for Erectile Dysfunction.
• Actual Study Start Date: May 21, 2020
• Estimated Primary Completion Date: September 1, 2021
• Estimated Study Completion Date: September 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PRP group; Participants in this group will receive 2 sessions of autologous PRP penile injection, each administered 1 month apart ± 7 days	Drug: Autologous Platelet Rich Plasma; Each injection session will consist of a total of 10 mL PRP infused slowly over a 2-minute period; 5 mL each injected to the right and left corpus cavernosum.; Other Name: PRP
Placebo Comparator: Placebo group; Participants in this group will receive 2 sessions of placebo injection, each administered 1 month apart ± 7 days.	Other: Saline solution; Each injection session will consist of a total of 10 mL saline solution infused slowly over a 2-minute period; 5 mL s each injected to the right and left corpus cavernosum

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants achieving MCID in IIEF-EF [ Time Frame: 9 weeks ]
   Treatment efficacy of PRP will be assessed via the percentage of participants achieving mild clinically important difference (MCID) in their IIEF-EF scores from baseline to 4 weeks after final treatment. International Index of Erectile Function - Erectile Function Subdomain Score (IIEF-EF) is a 5-item subdomain self- evaluation questionnaire of erectile function with a total score ranging from 0-25 with the higher score indicating better erectile function. MCID is attained via an increase of 2 points in IIEF-EF score for participants with mild ED and an increase of 5 points for participants with moderate ED.

Secondary Outcome Measures :

1. Percentage of participants achieving MCID in IIEF-EF [ Time Frame: 24 weeks ]
   Treatment efficacy of PRP will be assessed via the percentage of participants achieving MCID in their IIEF-EF scores from baseline to 2 and 24 weeks after final treatment. IIEF-EF is a 5-item subdomain self- evaluation questionnaire of erectile function with a total score ranging from 0-25 with the higher score indicating better erectile function. MCID is attained via an increase of 2 points in IIEF-EF score for participants with mild ED and an increase of 5 points for participants with moderate ED.
2. Change in IIEF-EF Scores [ Time Frame: Baseline up to Week 9, Baseline up to Week 17, Baseline up to Week 29 ]
   IIEF-EF is a 5-item subdomain self-evaluation questionnaire of erectile function. Each item is scored from 0-5 with the total score ranging from 0-25 with the higher score indicating better erectile function.
3. Change in doppler ultrasound parameters [ Time Frame: Baseline, Up to 29 weeks ]
   Change in Peak Systolic Velocity (PSV) and End Diastolic Velocity (EDV) assessed in cm/sec via ultrasound.
4. Incidence of adverse events [ Time Frame: 24 weeks ]
   Safety will be evaluated via the incidence of adverse events as assessed by treating physician

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be Male
2. Be 30 to 75 years of age (inclusive).
3. Be able to provide written informed consent.
4. Have a diagnosis of ED due to organic origin for at least 6 months prior to consent.
5. Sexually active in a stable, heterosexual relationship of more than three months duration.
6. IIEF-EF score 11-25 at screening (even if taking a single PDE5).
7. Agree to attempt sexual intercourse at least 4 times per month for the duration of the study without being under the influence of alcohol or recreational drugs.
8. Agree to comply with all study related tests/procedures.

Exclusion Criteria:

1. Previous penile surgery of any kind (except circumcision and condyloma removal), such as penile lengthening, penile cancer surgery, penile plication, grafting.
2. Previous history of priapism or penile fracture
3. Abnormal morning serum testosterone level defined as a value lower than 300 ng/dL (±5%) (indicative of untreated hypogonadism), or greater than 1197 ng/dL (±5%).
4. Current or previous hormone usage, other than prescribed testosterone, clomiphene or thyroid medication. (Subjects with prior or current use of hormonal treatment for prostate cancer are also excluded.
5. Psychogenic ED as determined by study investigator.
6. Anatomical (Peyronie's Disease or penile curvature that negatively influences sexual activity) or neurological abnormalities in the treatment area.
7. Patients using Intra Cavernous Injection (ICI)for management of ED
8. Patients with generalized polyneuropathy, or neurological conditions irrespective of cause, such as severe diabetes, multiple sclerosis or Parkinson's disease.
9. Have a serious comorbid illness/condition/behavior that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.
10. History of consistent treatment failure with PDE5 inhibitors for therapy of ED.
11. Any history of significant psychiatric disease, such as bipolar disorder or psychosis, greater than one lifetime episode of major depression, current depression of moderate or greater severity. Patients who are currently using Selective Serotonin Reuptake Inhibitor or psychotropic medications.
12. Hemoglobin a1c >9%.

Contacts and Locations

Contacts

Contact: Thomas Masterson, MD; 305-243-4562; tmasterson@med.miami.edu

Contact: Ranjith Ramasamy, MD; 305-243-4562; ramasamy@miami.edu

Locations

United States, Florida

University of Miami Miller School of Medicine; Recruiting

Miami, Florida, United States, 33136

Contact: Ranjith Ramasamy, MD 305-243-4562 ramasamy@miami.edu

Sponsors and Collaborators

University of Miami

Investigators

• Principal Investigator: Ranjith Ramasamy, MD; University of Miami

More Information

Publications:

Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013 Dec;9(12):721-30. doi: 10.1038/nrrheum.2013.141. Epub 2013 Oct 1. Review.

Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008 Dec;1(3-4):165-74. doi: 10.1007/s12178-008-9032-5.

Xie X, Zhang C, Tuan RS. Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis Res Ther. 2014 Feb 25;16(1):204. Review.

Randelli P, Randelli F, Ragone V, Menon A, D'Ambrosi R, Cucchi D, Cabitza P, Banfi G. Regenerative medicine in rotator cuff injuries. Biomed Res Int. 2014;2014:129515. doi: 10.1155/2014/129515. Epub 2014 Aug 13. Review.

Galliera E, Corsi MM, Banfi G. Platelet rich plasma therapy: inflammatory molecules involved in tissue healing. J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2 Suppl 1):35S-42S. Review.

Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci. 2008 May 1;13:3532-48. Review.

Lin G, Shindel AW, Fandel TM, Bella AJ, Lin CS, Lue TF. Neurotrophic effects of brain-derived neurotrophic factor and vascular endothelial growth factor in major pelvic ganglia of young and aged rats. BJU Int. 2010 Jan;105(1):114-20. doi: 10.1111/j.1464-410X.2009.08647.x. Epub 2009 Jun 2.

Apel PJ, Ma J, Callahan M, Northam CN, Alton TB, Sonntag WE, Li Z. Effect of locally delivered IGF-1 on nerve regeneration during aging: an experimental study in rats. Muscle Nerve. 2010 Mar;41(3):335-41. doi: 10.1002/mus.21485.

Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003 Jul;83(3):835-70. Review.

Kushida S, Kakudo N, Morimoto N, Hara T, Ogawa T, Mitsui T, Kusumoto K. Platelet and growth factor concentrations in activated platelet-rich plasma: a comparison of seven commercial separation systems. J Artif Organs. 2014 Jun;17(2):186-92. doi: 10.1007/s10047-014-0761-5. Epub 2014 Apr 20.

• Responsible Party: Ranjith Ramasamy, MD, Director of Male Fertility and Andrology, University of Miami, University of Miami
• ClinicalTrials.gov Identifier: NCT04396795
• Other Study ID Numbers: 20200373
• First Posted: May 21, 2020
• Last Update Posted: September 18, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ranjith Ramasamy, MD, University of Miami:

ED

Additional relevant MeSH terms:

Erectile Dysfunction; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Mental Disorders