Pilot Study of MRI-Guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids

Uterine Fibroids Clinical Trial

Official title:

Pilot Study of MRI-Guided High Intensity Focused Ultrasound Ablation of Uterine Fibroids

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00837161
• Other study ID #: 994043
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 4, 2009
• Last updated: November 30, 2012
• Start date: January 2009
• Est. completion date: December 2010

Study information

• Verified date: November 2012
• Source: Philips Healthcare
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 59 Years

Eligibility

• INCLUSION CRITERIA:

1. Recommended for Total Abdominal Hysterectomy

2. Age between 18 and 59

3. Weight less than 140kg (or 310lbs)

4. Pre or peri menopausal with FSH less than 40 mIU/ml

5. Uterine size less than 24 weeks based on MRI and physical exam assessment

6. Symptom severity score greater than or equal to 50 by Spies Uterine Fibroid Questionnaire.

7. Cervical cytology no more severe than low grade SIL

8. History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the ACOG practice bulletin (ACOG Practice Bulletin 1994):

9. Dominant intramural fibroid greater than or equal to 3 cm and less than or equal to 16 cm on imaging.

EXCLUSION CRITERIA:

1. Other pelvic disease (mass indicated by history or MR imaging such as endometriosis, ovarian tumor, acute or chronic pelvic inflammatory disease)

2. Desire for future pregnancy

3. Significant systemic disease even if controlled

4. Pregnant or Positive pregnancy test

5. Hematocrit less than 25%

6. Extensive scarring along anterior lower abdominal wall (greater than 50% of area) or scar tissue or surgical clips in the direct path of the HIFU beam

7. MRI or MRI contrast agent contraindicated

8. Unable to quantify or measure fibroids on MR exam including nonenhancing fibroids

9. Fibroid or uterine calcifications

10. Dominant fibroid is pedunculated or greater than 5 cm submucosal

11. Communication barrier

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leiomyoma
• Uterine Fibroids
• Uterine Leiomyomata

Intervention

Device:
• Philips MR guided HIFU system
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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	St. Luke's Episcopal Hospital	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Philips Healthcare

Country where clinical trial is conducted

United States, 

References & Publications (3)

Fennessy FM, Tempany CM, McDannold NJ, So MJ, Hesley G, Gostout B, Kim HS, Holland GA, Sarti DA, Hynynen K, Jolesz FA, Stewart EA. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology. 2007 Jun;243(3):885-93. Epub 2007 Apr 19. — View Citation

Flynn M, Jamison M, Datta S, Myers E. Health care resource use for uterine fibroid tumors in the United States. Am J Obstet Gynecol. 2006 Oct;195(4):955-64. Epub 2006 May 24. — View Citation

Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynyen K, Mcdannold N, Inbar Y, Itzchak Y, Rabinovici J, Kim HS, Geschwind JF, Hesley G, Gostout B, Ehrenstein T, Hengst S, Sklair-Levy M, Shushan A, Jolesz F. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol. 2004 Dec;183(6):1713-9. Erratum in: AJR Am J Roentgenol. 2005 Jan;184(1):348. Hynnen, Kullvro [corrected to Hynyen, Kullervo]; Macdanold, Nathan [corrected to Mcdannold, Nathan]; Kim, Kevin [corrected to Kim, Hyun S]; Gostout, Brian [corrected to Gostout, Bobbie]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related Adverse Events (AE) Per Subject Resulting From HIFU Treatment of the Uterine Fibroids	The number of treatment-related Adverse Events (AE) reported during the study, divided by the total number of treated subjects. This corresponds to the mean number of treatment-related Adverse Events per subject. Relatedness of an AE to the treatment was judged case-by-case by the investigator.	end of follow-up (date of hysterectomy, at latest day 30 after treatment)	Yes
Secondary	HIFU Treatment Equals Location Per Hysterectomy	Count the number of participants in which both of the following conditions are satisfied: the fibroid treated area as shown on MRI images during treatment is the same as displayed on fibroids from histology slices after hysterectomy, and no unintended lesions are visible in the uterus.	Day 0, Hysterectomy	Yes
Secondary	Length of Time to Return to Normal Activities	Length of time to return to normal activity measured in number of days from HIFU treatment. Assessed by patient interviews during follow-up.	end of follow-up (date of hysterectomy, at latest day 30 after treatment)]	No
Secondary	Numerical Range Scale (NRS) of Pain Level	Pain Scores obtained by patient self-assessment on a 0-10 scale, with 0 corresponding to no pain and 10 corresponding to maximum pain.	Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks	No
Secondary	Discomfort Level	Patient's self-assessed discomfort level on a 4-point scale, with: 0 = no pain; 1 = mild; 2 = moderate; 3 = severe.	Treatment Day: Baseline, Recovery, Discharge; Follow-up: 24 hours, 48 hours, 72 hours, 1 week, 2 weeks	No