Shockwave Therapy + Xiaflex for Peyronie's Disease

Overseen By Wyatt H Anians, CCRP

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Prior PD surgery, Severe penile pain, Moderate ED, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for Peyronie's Disease, which causes the penis to curve due to scar tissue. Researchers aim to determine if low-intensity shockwave therapy combined with Xiaflex, an injectable medication, improves curvature more effectively than Xiaflex alone. Individuals who have had Peyronie's Disease for over six months and have a noticeable but not severe curve may qualify for this study. As an unphased trial, this study provides a unique opportunity to explore innovative treatment combinations that could enhance quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Collagenase Clostridium Histolyticum (CCH) is generally safe for patients with Peyronie's disease. Studies have found that this treatment can reduce penile curvature by about 27.4% to 37.4% without causing unusual side effects. CCH is also the only FDA-approved treatment for this condition, supported by large studies.

The safety of adding low-intensity shockwave therapy (LiSWT) to CCH is still under investigation. However, LiSWT alone has been used to treat Peyronie's disease and is believed to alleviate symptoms like bending and pain. Researchers are closely monitoring the safety of this combination to ensure it is safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Collagenase Clostridium Histolyticum (CCH) with low-intensity shockwave therapy (LiSWT) for Peyronie's Disease because it offers a novel approach that enhances current treatments. Most treatments for Peyronie's Disease, like standalone CCH injections, primarily work by breaking down the excess collagen causing penile curvature. However, adding LiSWT to CCH might increase effectiveness by using sound waves to promote tissue healing and reduce plaque. This dual approach could provide more significant improvements in curvature and symptoms compared to the existing standard of care.

What evidence suggests that this trial's treatments could be effective for Peyronie's Disease?

Research has shown that a treatment called Collagenase Clostridium Histolyticum (CCH) can reduce penile curvature in Peyronie's Disease. A major study reported a 34% reduction in curvature, with an average improvement of 17 degrees. Patients also experienced symptom relief and improved quality of life.

In this trial, one group of participants will receive CCH alone, while another group will receive CCH combined with low-intensity shockwave therapy (LiSWT). Studies suggest that adding LiSWT to CCH might offer additional benefits, such as reducing the size of the hardened tissue (plaque) and further improving curvature or reducing pain. Together, these treatments aim to provide better outcomes for people with Peyronie's Disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Tobias Kohler, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Men with Peyronie's Disease (PD) who have a significant bend in their penis (30-90 degrees), can feel the plaque causing the curve, and whose symptoms have been stable for at least 3 months. They shouldn't have had previous treatments for PD, severe pain or erectile dysfunction, certain types of penile curvature, or heavy plaque calcification.

Inclusion Criteria

I have been diagnosed with Parkinson's disease.

Non-calcified plaque or grade 1 calcification ("stippling", no shadowing) as determined by penile duplex Doppler ultrasound (PDDU)

I can feel a lump in my penis.

Exclusion Criteria

I have had shockwave therapy for sexual dysfunction.

I have had injections or surgery for Peyronie's disease.

I have moderate to severe erectile dysfunction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Collagenase Clostridium Histolyticum (CCH) intralesional injection with or without low-intensity shockwave therapy (LiSWT)

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Collagenase Clostridium Histolyticum
• Low Intensity Shockwave Therapy

Trial Overview The trial is testing if combining low-intensity shockwave therapy with Xiaflex injections improves straightening of the penis better than previous treatments alone. Participants will receive both therapies to see if there's greater improvement in penile curvature.

How Is the Trial Designed?

Group I: Collagenase Clostridium Histolyticum with Low Intensity Shockwave Therapy Experimental Treatment 2 Interventions

Subjects will receive Collagenase Clostridium Histolyticum (CCH) intralesional injection with low-intensity shockwave therapy (LiSWT).

Group II: Collagenase Clostridium Histolyticum Active Control 1 Intervention

Subjects will receive Collagenase Clostridium Histolyticum (CCH) intralesional injection per standard of care.

Collagenase Clostridium Histolyticum is already approved in United States, European Union for the following indications:

Approved in United States as Xiaflex for:

• Peyronie's disease
• Dupuytren's contracture

Approved in European Union as Xiaflex for:

• Peyronie's disease
• Dupuytren's contracture

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a phase 3 study involving 347 men with Peyronie's disease, collagenase clostridium histolyticum (CCH) demonstrated a significant mean improvement of 34.4% in penile curvature deformity and a reduction of 3.3 points in the PD symptom bother score after 36 weeks of treatment.

CCH was generally well tolerated, with most adverse events being mild or moderate, and only three serious treatment-related adverse events were reported, all of which resolved with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study. Levine, LA., Cuzin, B., Mark, S., et al.[2022]

In a study of 53 patients with Peyronie's disease, a new modified treatment protocol using only three injections of collagenase clostridium histolyticum (CCH) resulted in a significant improvement in penile curvature, with 96.2% of patients showing an average reduction of 17.36° from a baseline curvature of 54° (P < 0.001).

The modified protocol was found to be safe and well-tolerated, with only mild and transient local side effects, and its efficacy was comparable to traditional protocols that required eight injections, making it a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of collagenase clostridium histolyticum in the treatment of Peyronie's disease using a new modified shortened protocol. Abdel Raheem, A., Capece, M., Kalejaiye, O., et al.[2018]

Xiaflex, an injectable treatment for Peyronie's disease, has been found to be both safe and effective as a first-line therapy.

The study supports the use of collagenase Clostridium histolyticum injections, indicating they can effectively reduce the curvature associated with Peyronie's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xiaflex for Treatment of Peyronie's Disease. Shin, D., Shah, T., Sadeghi-Nejad, H.[2018]

Collagenase Clostridium histolyticum (CCH) is the first licensed non-surgical treatment for Peyronie's disease (PD), demonstrating safety and efficacy in large phase III trials (IMPRESS I and II) involving men with PD.

The authors introduced a new shortened modified protocol for CCH that maintains safety and efficacy while reducing treatment costs and duration, potentially increasing access for more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagenase Clostridium histolyticum in the Treatment of Peyronie's Disease-A Review of the Literature and a New Modified Protocol. Abdel Raheem, A., Johnson, M., Abdel-Raheem, T., et al.[2018]

A survey of 47 urology programs revealed that while 95.7% of residents receive training in evaluating and managing Peyronie's disease, only 66.0% receive training specifically on the non-surgical treatment with Xiaflex®, indicating a significant gap in exposure to this FDA-approved therapy.

Most training on Xiaflex® is provided by fellowship-trained sexual medicine faculty, but there is a need for more comprehensive exposure to ensure residents are well-prepared to use this treatment effectively in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of exposure to the use of Xiaflex for the treatment of Peyronie's disease among United States urology residency programs. Loloi, J., Schuppe, K., Reddy, RV., et al.[2023]

In a study of 450 stable Peyronie's disease patients, only 24.7% opted for intralesional collagenase (ILX) treatment, indicating that it is not the most common choice among patients.

Patients who chose ILX were more likely to experience significant bother and had more complex curvature and moderate to severe instability, suggesting that these factors are important predictors for deciding to pursue this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of Pursuing Intralesional Xiaflex in Peyronie's Disease Patients. Punjani, N., Nascimento, B., Salter, C., et al.[2022]

Collagenase Clostridium histolyticum (CCH), known as Xiaflex, is an effective non-surgical treatment for Peyronie's disease, but it can lead to rare complications such as lateral herniation of the tunica albuginea, as demonstrated in a case involving a 58-year-old male.

The patient experienced a painless swelling on the left side of the penis after CCH injections, indicating a potential herniation rather than a rupture, highlighting the need for awareness of this rare side effect during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateral herniation during treatment with collagenase Clostridium histolyticum (Xiaflex) for Peyronie's disease. Gannon, MK., Pearlman, AM.[2021]

In a study of 135 men with stable Peyronie's disease, a modified treatment protocol using Collagenase Clostridium histolyticum (CCH) injections significantly improved penile curvature by an average of 19.07 degrees and enhanced sexual function for both patients and their partners.

The treatment resulted in a high global satisfaction rate of 89.6%, indicating that CCH injections not only benefited the patients but also positively impacted their partners' sexual function, although the study had limitations such as the lack of a placebo group and long-term follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Factors of Patients' and Their Partners' Sexual Function Improvement After Collagenase Clostridium Histolyticum Injection for Peyronie's Disease: Results From a Multi-Center Single-Arm Study. Cocci, A., Russo, GI., Salonia, A., et al.[2019]

In a study of 918 patients with Peyronie's disease, treatment with collagenase Clostridium histolyticum resulted in a significant improvement in penile curvature, reducing the average curvature from 48.2 degrees to 32.9 degrees, which is a 30.1% improvement.

The treatment was found to be safe, with only 9% of patients experiencing complications, and the number of treatment cycles was positively correlated with the degree of curvature improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intralesional Collagenase Clostridium histolyticum Causes Meaningful Improvement in Men with Peyronie's Disease: Results of a Multi-Institutional Analysis. Hellstrom, WJG., Tue Nguyen, HM., Alzweri, L., et al.[2019]

In a phase 2b study involving 147 subjects, collagenase Clostridium histolyticum significantly improved penile curvature by 29.7% compared to 11.0% in the placebo group, indicating its efficacy as a treatment for Peyronie disease.

The treatment was well tolerated with mostly mild to moderate adverse events occurring at the injection site, and no serious treatment-related adverse events were reported, suggesting it is a safe nonsurgical option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2b study of the clinical efficacy and safety of collagenase Clostridium histolyticum in patients with Peyronie disease. Gelbard, M., Lipshultz, LI., Tursi, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8451611/

Peyronie's disease – outcomes of collagenase clostridium ... The capstone CCh study was the IMPRESS trial thatshowed a 34% reduction in curvature with a mean (SD) – 17.0 (14.8)° reduction with IL CCh,while men in the ...

2. peyronies-disease.xiaflex.com peyronies-disease.xiaflex.com/hcp/efficacy-safety/study-design/

Study Design XIAFLEX is the only FDA-approved treatment evaluated in 2 large multicenter studies of patients with Peyronie's disease (PD).

3. academic.oup.com academic.oup.com/smr/article/12/3/497/7655837

Efficacy of collagenase Clostridium histolyticum combination ... In meta-analyses of CCH combined treatment for PD disease, results consistently showed significant improvements in penile length, PDQ-SB, and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0090429522008305

Improved Peyronie's Disease Curvature Outcomes Using a ... Results from the current study demonstrate significantly greater curvature and subjective improvements among men treated with a novel, more aggressive CCH ...

5. nature.com nature.com/articles/s41443-018-0027-5

Patient perspectives on Peyronie's disease: results of ... Treatment with CCH improved PD symptoms (44.4%), frequency of or ability to have vaginal intercourse (22.2%) and partner relationship (22.2%), particularly ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25388099/

Clinical safety and effectiveness of collagenase clostridium ... Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study · Authors.

7. academic.oup.com academic.oup.com/jsm/article/22/5/794/8113152

Are patients undergoing intralesional collagenase Clostridium ... Overall compliance rate for CCH injection therapy was 70.89%. Greater curvature reduction was demonstrated in compliant patients. Common reasons ...

8. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.780956/full

Efficacy and Safety of Collagenase Clostridium ... Collagenase Clostridium Histolyticum (CCH) has shown its effectiveness in treating PD, but its efficacy and safety remain controversial.