ITU: Intense Therapeutic Ultrasound - Treatment for Chronic Plantar Fascia Musculoskeletal Pain Reduction

• Sponsor: Guided Therapy Systems (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03255655
• Collaborator: University of Arizona (Other)
• Enrollment: 41
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.3
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Double-blinded feasibility study for the treatment of pain related to chronic plantar fasciitis. A total 37 patients (27 treated and 12 control/sham treated) received 2 treatments, 2 weeks apart on subcutaneous plantar fascia musculoskeletal tissue along with Standard of Care treatments as prescribed by the Principal Investigator. Patients were followed for up to 6 months after the first treatment receiving a physical exam at each follow-up visit (4, 8 and 12 weeks) and provided feedback via Patient/Subject Reported Outcome Measure surveys specific to the treated anatomy at each visit and via phone follow-up at 26 weeks after the first treatment.

Condition or Disease	Intervention/Treatment	Phase
Chronic Plantar Fasciitis	Device: Intense Therapeutic Ultrasound Treatment - ITU	N/A

Detailed Description

Intense therapeutic ultrasound (ITU) is an established ultrasound based therapy in which sound waves are concentrated and focused into selected musculoskeletal tissue, to produce selective thermal coagulative changes over a small controlled area while leaving the surrounding tissue unaffected. These coagulative changes are known to begin the body's tissue response cascade and promote collagen generation in the targeted anatomy resulting in pain reduction.

ITU has been used clinically for treating the subcutaneous musculoskeletal tissue below facial skin for the past decade and it has received CE Mark and FDA 510(k) clearance to market for non-surgical brow and submental tissue lifting. Over 3 Million patients worldwide have been treated using this technology. Clinical studies have shown that 85% of patients receiving this treatment on facial skin tissue showed an improvement in facial lifting with no significant pain, erythema, inflammation or scarring by creating the same coagulative changes to the connective tissue under the skin. Histologically, it has been shown that ITU induces the production of dermal collagen with thickening of the dermis and straightening of the elastic fibers in the reticular dermis.

On-going research in laboratory studies has shown that ITU can improve healing of damaged Achilles tendon in a rabbit model. Preliminary results showed an increase in precursor markers for collagen regeneration (e.g. Vascular endothelial growth factor A (VEGFa), tumor necrosis factor alpha (TNFα), Interleukin 1 beta (IL-1β), and Transforming growth factor beta 1 (TGFβ1)) and subsequent increase in collagen formation in injured rabbit tendons treated with ITU compared to injured, untreated rabbit tendons.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Adult Patients (age 18 - 85) of either gender diagnosed with chronic plantar fasciitis pain (>90 days) where Standard of Care treatments had failed to reduce pain.Adult Patients (age 18 - 85) of either gender diagnosed with chronic plantar fasciitis pain (>90 days) where Standard of Care treatments had failed to reduce pain.
• Masking: Single (Investigator)
• Masking Description: Investigator was blinded to the treated vs. control/sham treated patient identity and to the treated foot. Researchers were blinded to the Investigators physical exam finding and patient outcome measure reports
• Primary Purpose: Treatment
• Official Title: Intense Therapeutic Ultrasound for Chronic Plantar Fascia Musculoskeletal Pain Reduction
• Actual Study Start Date: Oct 22, 2014
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ITU Treatment Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart.	Device: Intense Therapeutic Ultrasound Treatment - ITU; Other Names: Guided Therapy Systems, Ardent Sound, GTS, ITU
Placebo Comparator: Sham ITU Treatment Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart.	Device: Intense Therapeutic Ultrasound Treatment - ITU; Other Names: Guided Therapy Systems, Ardent Sound, GTS, ITU

Outcome Measures

Primary Outcome Measures

1. Average Percentage of Change as Reported Using Foot Function Index Pain Subscale [12 weeks after 1st Treatment]

   Average Percentage of Change as Reported using Foot Function Index (FFI) pain subscale. Range (±100%). Foot Function Index pain subscale is a measure of pain and disability and activity limitation based 9 questions, each with a possible pain score of 0 - 10, where 0 indicates no pain during the described activity and 10 indicates the worst imaginable pain during a described activity. A summed total score of 0 indicates the patient had no pain for all activities. A score of 90 indicates the patient experiences the worst imaginable pain for all the described activities. The results compare the average percentage change of the FFI score at 12 weeks, compared to the average FFI score at baseline.

2. Mean Percentage Change in Volume of Plantar Fascia Hypoechoic Lesions by Diagnostic Ultrasound Imaging [12 Weeks after the first Treatment]

   Mean Percentage Change in Volume of Plantar Fascia Hypoechoic Lesions by Diagnostic Ultrasound Imaging compared to Baseline Volume, where volume is calculated using: (4/3)π x R1 x R2 x R3, where R = Radius of each measurement: Lesion Length (1), Width (2), Depth (3).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• • Chronic Pain (>90 days) from previously diagnosed Plantar Fasciitis, where "Standard of Care" regimens failed to relief pain in the affected anatomy.

• No History of surgery to the affected anatomy.

• No alternative treatment procedures within the last 90 days.

• Unilateral Pain

• Willingness to complete treatment and post treatment regimen as described.

• Patients who have provided written and verbal informed consent

Exclusion Criteria:

• • Patients currently enrolled in any other non-conservative, device, or Investigational New Drug clinical trial, or who have participated in a clinical study involving the Plantar Fascia, thirty days prior to study initiation;

• Patients who have participated in any other clinical study involving an investigational product 30 days prior to enrollment that, in the opinion of the Principal Investigator, could affect the outcome of this study;

• Patients who have received previous treatment in the symptomatic limb (not including conservative treatment);

• At the Principal Investigator's discretion, any patient that should be excluded based on their current condition or medical history.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Univesity of Arizona; Orthopaedic Surgery and Biomedical Engineering	Tucson	Arizona	United States	85724

Sponsors and Collaborators

• Guided Therapy Systems
• University of Arizona

Investigators

• Principal Investigator: Dan Latt, Md, Ph.D., University of Arizona; Orthopaedic Surgery and Biomedical Engineering; Department of Orthopaedic Surgery

Study Documents (Full-Text)

• Study Protocol - Apr 5, 2014
• Informed Consent Form - May 23, 2014
• Statistical Analysis Plan - May 23, 2014

More Information

Publications

• Alam M, White LE, Martin N, Witherspoon J, Yoo S, West DP. Ultrasound tightening of facial and neck skin: a rater-blinded prospective cohort study. J Am Acad Dermatol. 2010 Feb;62(2):262-9. doi: 10.1016/j.jaad.2009.06.039.
• DiGiovanni BF, Nawoczenski DA, Lintal ME, Moore EA, Murray JC, Wilding GE, Baumhauer JF. Tissue-specific plantar fascia-stretching exercise enhances outcomes in patients with chronic heel pain. A prospective, randomized study. J Bone Joint Surg Am. 2003 Jul;85(7):1270-7.
• Gliklich RE, White WM, Slayton MH, Barthe PG, Makin IR. Clinical pilot study of intense ultrasound therapy to deep dermal facial skin and subcutaneous tissues. Arch Facial Plast Surg. 2007 Mar-Apr;9(2):88-95.
• Laubach HJ, Makin IR, Barthe PG, Slayton MH, Manstein D. Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin. Dermatol Surg. 2008 May;34(5):727-34. doi: 10.1111/j.1524-4725.2008.34196.x.
• Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33(5):381-94. Review.
• White WM, Makin IR, Barthe PG, Slayton MH, Gliklich RE. Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation. Arch Facial Plast Surg. 2007 Jan-Feb;9(1):22-9.

• Responsible Party: Guided Therapy Systems
• ClinicalTrials.gov Identifier: NCT03255655
• Other Study ID Numbers: GTS - ITU UA Plantar Fascia 01
• First Posted: Aug 21, 2017
• Last Update Posted: Dec 13, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Guided Therapy Systems: Chronic Plantar Fasciitis; Plantar Fascia Pain; Intense Therapeutic Ultrasound (ITU); Guided Therapy Systems (GTS); Ardent Sound, Inc.; Actisound
• Additional relevant MeSH terms: Musculoskeletal Pain; Fasciitis; Fasciitis, Plantar

Study Results

Participant Flow

Recruitment Details	Patients 18 - 85 years previously diagnosed with unilateral Chronic Plantar Fasciitis (>90 days), where Standard of Care therapies had failed to reduce pain.

Arm/Group Title	ITU Treatment for Chronic Plantar Fasciitis	Sham ITU Treatment for Chronic Plantar Fasciitis
Arm/Group Description	Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU	Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU
Period Title: Overall Study
STARTED	29	12
COMPLETED	22	8
NOT COMPLETED	7	4

Baseline Characteristics

Arm/Group Title	ITU Treatment for Chronic Plantar Fasciitis	Sham ITU Treatment for Chronic Plantar Fasciitis	Total
Arm/Group Description	Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU	Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU	Total of all reporting groups
Overall Participants	29	12	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 96.6%	11 91.7%	39 95.1%
>=65 years	1 3.4%	1 8.3%	2 4.9%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54	47	51
Sex: Female, Male (Count of Participants)
Female	24 82.8%	8 66.7%	32 78%
Male	5 17.2%	4 33.3%	9 22%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	29 100%	12 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Average Percentage of Change as Reported Using Foot Function Index Pain Subscale
Description	Average Percentage of Change as Reported using Foot Function Index (FFI) pain subscale. Range (±100%). Foot Function Index pain subscale is a measure of pain and disability and activity limitation based 9 questions, each with a possible pain score of 0 - 10, where 0 indicates no pain during the described activity and 10 indicates the worst imaginable pain during a described activity. A summed total score of 0 indicates the patient had no pain for all activities. A score of 90 indicates the patient experiences the worst imaginable pain for all the described activities. The results compare the average percentage change of the FFI score at 12 weeks, compared to the average FFI score at baseline.
Time Frame	12 weeks after 1st Treatment

Outcome Measure Data

Analysis Population Description

Total population of respondents at 12 weeks.

Arm/Group Title	ITU Treatment for Chronic Plantar Fasciitis	Sham ITU Treatment for Chronic Plantar Fasciitis
Arm/Group Description	Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU	Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU
Measure Participants	22	8
Mean (Full Range) [percentage of Change]	-54	-25

2. Primary Outcome

Title	Mean Percentage Change in Volume of Plantar Fascia Hypoechoic Lesions by Diagnostic Ultrasound Imaging
Description	Mean Percentage Change in Volume of Plantar Fascia Hypoechoic Lesions by Diagnostic Ultrasound Imaging compared to Baseline Volume, where volume is calculated using: (4/3)π x R1 x R2 x R3, where R = Radius of each measurement: Lesion Length (1), Width (2), Depth (3).
Time Frame	12 Weeks after the first Treatment

Outcome Measure Data

Analysis Population Description

Male and Female previously diagnosed with Chronic Plantar Fasciitis, between the age of 18 and 85.

Arm/Group Title	ITU Treatment for Chronic Plantar Fasciitis	Sham ITU Treatment for Chronic Plantar Fasciitis
Arm/Group Description	Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU	Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU
Measure Participants	22	8
Mean (Standard Error) [percentage of Hypoechoic Lesion Change]	-81 (8)	26 (4)

Adverse Events

Time Frame	2 years, 9 months
Adverse Event Reporting Description	Any Patient Self-Reported Adverse Event occurring during the treatment or during the Follow-up Period.
Arm/Group Title	ITU Treatment for Chronic Plantar Fasciitis		Sham ITU Treatment for Chronic Plantar Fasciitis
Arm/Group Description	Intense Therapeutic Ultrasound (ITU) treatment applied along the length and width of the Plantar Fascia: 350 - 5 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU		Sham / Placebo Intense Therapeutic Ultrasound treatment (ITU) applied along the length and width of the Plantar Fascia: 350 - 0 Joule pulses were applied twice, two weeks apart. Intense Therapeutic Ultrasound Treatment - ITU
All Cause Mortality
	ITU Treatment for Chronic Plantar Fasciitis		Sham ITU Treatment for Chronic Plantar Fasciitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ITU Treatment for Chronic Plantar Fasciitis		Sham ITU Treatment for Chronic Plantar Fasciitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	ITU Treatment for Chronic Plantar Fasciitis		Sham ITU Treatment for Chronic Plantar Fasciitis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.