Extracorporeal Shockwave Therapy (ESWT) for the Management of Stress Fractures and High-grade Bone Stress Injuries (BSIs)

A Randomized, Double-blind, Dose-escalation, Sham-controlled Trial to Evaluate the Safety and Feasibility of Extracorporeal Shockwave Therapy (ESWT) for the Management of Stress Fractures and High-grade Bone Stress Injuries (BSIs)

The goal of this clinical trial is to evaluate the clinical safety and efficacy of Extracorporeal Shockwave Therapy (ESWT) for the management of high-grade Bone Stress Injuries (BSIs) in collegiate and recreational athletes compared to a control group receiving standard of care with sham ESWT.

The primary and secondary endpoints of the study are to evaluate the safety and feasibility of extracorporeal shockwave therapy for the treatment of pelvic and lower limb extremity fracture or BSI.

Researchers will compare the ESWT group to the sham ESWT group to see if ESWT results in better safety and efficacy outcomes for treating high-grade BSIs.

Participants will:

• Undergo a screening period to determine eligibility.
• Receive up to 4 treatment sessions of ESWT, with the frequency of sessions being approximately every 5 days (within a range of every 3-10 days).
• Be monitored for up to 6 months for research follow-up, with further questionnaires and check-ins during the standard of care follow-up period until they are able to return to sport activity level.

Extracorporeal shockwave treatment (ESWT) administered using the SANUWAVE Profile ESWT device is an established therapeutic modality that uses focused shockwaves through an electrohydraulic process that uses higher energy per unit area.

Each subject will receive treatment: the goal for each participant is to receive a total of 4 treatment sessions, with the frequency of treatment being one treatment on average every 5 days (permitted frequency every 3-10 days).

The treatment and care of bone stress injuries will depend on the injury site identified for the subject as noted in Table 1 of the protocol. The initial treatment will be set at lower energy settings and will increase using standard language delivered to the patient for Treatment Sessions 2-4.

Subjects will be monitored for a period of up to 6 months for research follow-up. Standard of care follow-up period begins in which subjects will receive questionnaires and check-ins to monitor for adverse events until the subject is determined to be able to return to sport activity level. If subjects have serious questions, they will be advised to speak with their treating physician.

In total, subjects are to participate for a duration of 8 months. The total study duration for recruitment, enrollment, and study completion of all subjects will last up to 3 years.

UCLA will serve as the IRB of record for all sites, and all sites will conduct the study as described in this application.

Inclusion Criteria:

• Male or female 18 - 50 years of age who engage in greater than or equal to 2.5 hours a week of physical activity (in any sport, with the primary aim to maintain health and fitness), at screening.
• Documentation of pelvic or lower extremity BSI diagnosis as evidenced by one or more clinical features consistent with the high-grade BSI by MRI grading (stress reactions of MRI grade 3 or stress fracture, grade 4 by Fredericson MRI Grading) with specific stress injury sites to be included: pelvis (including pubic ramus and sacrum), compression-sided femoral neck with fracture line less than 50% diameter if grade 4, femoral shaft, posteromedial tibia, calcaneus, metatarsal (2nd-4th, excluding proximal 2nd), and fibula.
• Written informed consent obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
• If on NSAIDs, willing to refrain from use during the study.
• If female of child-bearing potential, both of the following must be met at screening:
• Practices one of the following methods of contraception and continues through the duration of the study: abstinence, hormonal contraceptives, IUD, spermicide and barrier or implantable device, and
• Has a negative urine qualitative beta-HCG pregnancy test.
• If female and post-menopausal one of the following must be met at screening:
• Has had a complete hysterectomy, bilateral salpingo-oophorectomy or tubal ligation or otherwise be incapable of pregnancy, or
• Is postmenopausal for at least one year.

Exclusion Criteria:

• Pregnant, breastfeeding, plans to become pregnant during the study, or unwilling to practice birth control during participation in the study.
• Unsuitable candidate for the study, based on the opinion of the investigator (e.g. cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study.
• Subjects who, at entry, are known to have alternative treatment (e.g. surgery) planned within the next 8 weeks.
• History of severe osteoporosis (prior DXA scan with Z-score of -3.0 or T-score less than or equal to -2.5 and prior fracture history) or other underlying bone disease/disorder.
• Chronic rheumatologic condition and/or history of chronic oral steroid use.
• Type II diabetes, other chronic underlying disease.
• Morbid obesity (Body Mass Index greater than or equal to 35) at screening.
• Has clinically significant renal disease defined as having an estimated creatinine clearance of greater than or equal to 40mL/min at screening.
• History of osteomyelitis in the injured area on which the treatment is to be administered at screening.
• Has a current history of substance abuse (current is defined as within 120 days of screening).
• Has evidence of a prior fracture or BSI within the last 6 months in the same area as the current injury.
• Has active cellulitis or wound either at the injury site, or in the surrounding area at screening.
• Has an injury requiring surgical intervention at screening.
• Current/active DSM-V eating disorder diagnosis.
• History of vascular insufficiency.
• History of neurologic insufficiency.
• History of coagulopathy, including previous deep vein thrombosis within six months of Visit 1; and/or therapy with anticoagulation medication (e.g. warfarin).
• Radiation treatment within 120 days of Visit 1.
• Presence of malignant disease with or without metastases.
• Has a life expectancy of less than or equal to 2 years.
• History of sickle cell anemia.
• Has a known immunodeficiency disorder to include, but not be limited to: AIDS, HIV, etc.
• Has participated in another investigation within 30 days of Visit 1.
• Has previously received extracorporeal shockwave therapy (ESWT) with a SANUWAVE device.