Pilot Study of MRI-Guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids
Condition: Uterine Fibroids; Uterine Leiomyomata
MeSH terms: Leiomyoma; Myofibroma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Uterine fibroids (leiomyomas) are a common cause of heavy uterine bleeding and pain in
      reproductive aged women and are the most common cause of hysterectomy in the United States.
      Women are seeking new ways to treat symptomatic uterine fibroids that allow them to avoid
      surgery. This study is the first step in this quest. We will study the novel use of magnetic
      resonance imaging (MRI) in enhancing the safety of the FDA approved technique to treat
      fibroids called High Intensity Focused Ultrasound (HIFU). The term 'high intensity focused
      ultrasound' means using ultrasound to heat and to thermally destroy tissue, in this case,
      uterine fibroids. The MRI system will allow us to watch the ultrasound path during treatment
      and monitor the temperature increase in the fibroid tissue that comes during the procedure.

      In this pilot study, women with symptomatic fibroids will undergo MRI guided HIFU and then
      have a hysterectomy. This will allow us to confirm studies done in animals which show that it
      is possible to destroy specific tissue without harming normal tissue surrounding the targeted
      area.

      The purpose of this clinical study is to confirm the safety and treatment capabilities of the
      Philips MR guided HIFU system for ablation of uterine fibroids. This is a single arm pilot
      study of 10 women who will undergo hysterectomy after the HIFU procedure. This study design
      of hysterectomy after treatment has been requested by the FDA as part of IDE approval for
      this new device and mirrors what has been required for similar devices. Safety will be
      assessed by evaluating treatment accuracy, complications, and adverse events. Treatment
      capabilities will be assessed by evaluating the fibroid volume ablated and other factors
      related to the procedure feasibility and acceptance including procedure duration, time to
      return to normal activity, and pain scores at the time of the procedure.

      Study population

      The Philips MR-HIFU System is intended for ablation of uterine fibroid tissue in pre- or
      perimenopausal women with symptomatic uterine fibroids who desire a uterine-sparing
      procedure. Patients must have completed child bearing prior to enrolling in this study.
      Patients will be recruited by referral to gynecology and interventional radiology at the NIH
      Clinical Center. Candidates for enrollment will already have symptomatic uterine leiomyomas
      and be willing to undergo hysterectomy for treatment. It is estimated that of apparently
      eligible subjects, at least 30 women will have to be screened in person in order to identify
      10 who will be eligible for this study. Other studies of fibroid treatments are currently
      ongoing at the NIH. Women who have been interested in, but have not been selected for
      enrollment in those studies and who appear to be eligible to this study will be contacted for
      potential enrollment.

      Study design:

      This study is a multi-center, single arm trial evaluating the safety and treatment
      capabilities of the Philips MR-guided HIFU system in the treatment of symptomatic uterine
      fibroid patients who are otherwise healthy women. All patients enrolled in the study will
      undergo hysterectomy within a window of 30 days following HIFU treatment. Patients who have
      symptomatic uterine fibroids, meet clinical indications for hysterectomy, are eligible
      according to the inclusion and exclusion criteria and provide informed consent will be
      enrolled in this study. This study design of treatment followed by hysterectomy has been
      requested by the FDA as part of IDE approval for this new device and mirrors what has been
      required for similar devices. It is anticipated that women will participate in the study for
      a 3 month period to include the screening, HIFU treatment, hysterectomy and post hysterectomy
      follow-up.

      The methodology used for this HIFU device capitalizes on the thermal properties of volumetric
      ablation rather than point ablation used by other focused ultrasound systems. Thus it is
      anticipated that this device will have a shorter treatment time compared to other HIFU
      machines. This HIFU system, via real-time MR thermometry monitoring, has automated thermal
      feedback during the procedure which may enhance safety. This pilot study will not only assess
      the safety of this device but will enable us to delineate the treatment capabilities of this
      system for future use in patients who want uterine sparing non-surgical treatment for
      symptomatic fibroids.
    

Detailed description: 
      Uterine fibroids (leiomyomas) are a common cause of heavy uterine bleeding and pain in
      reproductive aged women and are the most common cause of hysterectomy in the United States.
      Women are seeking new ways to treat symptomatic uterine fibroids that allow them to avoid
      surgery. This study is the first step in this quest. We will study the novel use of magnetic
      resonance imaging (MRI) in enhancing the safety of the FDA approved technique to treat
      fibroids called High Intensity Focused Ultrasound (HIFU). The term high intensity focused
      ultrasound means using ultrasound to heat and to thermally destroy tissue, in this case,
      uterine fibroids. The MRI system will allow us to watch the ultrasound path during treatment
      and monitor the temperature increase in the fibroid tissue that comes during the procedure.

      In this pilot study, women with symptomatic fibroids will undergo MRI guided HIFU and then
      have a hysterectomy. This will allow us to confirm studies done in animals which show that it
      is possible to destroy specific tissue without harming normal tissue surrounding the targeted
      area.

      The purpose of this clinical study is to confirm the safety and treatment capabilities of the
      Philips MR guided HIFU system for ablation of uterine fibroids. This is a single arm pilot
      study of 10 women who will undergo hysterectomy after the HIFU procedure. This study design
      of hysterectomy after treatment has been requested by the FDA as part of IDE approval for
      this new device and mirrors what has been required for similar devices. Safety will be
      assessed by evaluating treatment accuracy, complications, and adverse events. Treatment
      capabilities will be assessed by evaluating the fibroid volume ablated and other factors
      related to the procedure feasibility and acceptance including procedure duration, time to
      return to normal activity, and pain scores at the time of the procedure.

      Study population

      The Philips MR-HIFU System is intended for ablation of uterine fibroid tissue in pre- or
      perimenopausal women with symptomatic uterine fibroids who desire a uterine-sparing
      procedure. Patients must have completed child bearing prior to enrolling in this study.
      Patients will be recruited by referral to gynecology and interventional radiology at the NIH
      Clinical Center. Candidates for enrollment will already have symptomatic uterine leiomyomas
      and be willing to undergo hysterectomy for treatment. It is estimated that of apparently
      eligible subjects, at least 30 women will have to be screened in person in order to identify
      10 who will be eligible for this study. Other studies of fibroid treatments are currently
      ongoing at the NIH. Women who have been interested in, but have not been selected for
      enrollment in those studies and who appear to be eligible to this study will be contacted for
      potential enrollment.

      Study design:

      This study is a multi-center, single arm trial evaluating the safety and treatment
      capabilities of the Philips MR-guided HIFU system in the treatment of symptomatic uterine
      fibroid patients who are otherwise healthy women. All patients enrolled in the study will
      undergo hysterectomy within a window of 30 days following HIFU treatment. Patients who have
      symptomatic uterine fibroids, meet clinical indications for hysterectomy, are eligible
      according to the inclusion and exclusion criteria and provide informed consent will be
      enrolled in this study. This study design of treatment followed by hysterectomy has been
      requested by the FDA as part of IDE approval for this new device and mirrors what has been
      required for similar devices. It is anticipated that women will participate in the study for
      a 3 month period to include the screening, HIFU treatment, hysterectomy and post hysterectomy
      follow-up.

      The methodology used for this HIFU device capitalizes on the thermal properties of volumetric
      ablation rather than point ablation used by other focused ultrasound systems. Thus it is
      anticipated that this device will have a shorter treatment time compared to other HIFU
      machines. This HIFU system, via real-time MR thermometry monitoring, has automated thermal
      feedback during the procedure which may enhance safety. This pilot study will not only assess
      the safety of this device but will enable us to delineate the treatment capabilities of this
      system for future use in patients who want uterine sparing non-surgical treatment for
      symptomatic fibroids.

      Primary Outcome parameters:

        1. Verifying with MR imaging that the location of the HIFU lesion matches the expected
           location (binary)

        2. Verifying with MR imaging that no unintended lesions are formed as a result of the
           treatment (binary)

        3. Examining the uterine capsule and surrounding areas for unintended damage during
           hysterectomy (binary)

        4. Evaluating any complications or adverse events that result from the MR-guided HIFU
           treatment (categorical)

        5. Comparing the actual MR-measured ablated volumes to MR thermal dose predicted volumes
           (categorical)

        6. Comparing the ablated volumes from histology to MR thermal dose predicated volume
           (categorical)

        7. Ensuring on histopathologic examination of the uterus that the zones treated by
           MR-guided HIFU treatment are indeed necrosed (binary)

      Secondary Outcome Parameters:

        1. Pain and discomfort scores immediately before, during and after HIFU treatment:

        2. Length of Hospital Stay (LOS)

        3. Return to Activity
    

Intervention name(s): Philips MR guided HIFU system
Intervention type(s): Device
Intervention description(s): HIFU is the use of focused ultrasound energy to penetrate through soft tissue and causes localized high temperatures (55°C to 70°C) for a few seconds within the target producing well defined regions of protein denaturation, irreversible cell damage, and coagulative necrosis
Other intervention name(s): Philips Sonalleve MR-HIFU system
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: High Intensity Focused Ultrasound Ablation; Uterine Fibroids; Leiomyomata; Non-Invasive Treatment of Uterine Fibroids; MRI-Guided; Fibroids; Uterine Leiomyomata