Targeted Reinnervation as a Means to Treat Neuromas Associated With Major Limb Amputation

Pain Clinical Trial

— TMR  

Official title:

Targeted Reinnervation as a Means to Treat Neuromas Associated With Major Limb Amputation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02205385
• Other study ID #: TMR Neuroma
• Secondary ID: OR120021
• Status: Completed
• Phase: N/A
• First received: July 23, 2014
• Last updated: January 1, 2018
• Start date: October 2014
• Est. completion date: January 1, 2018

Study information

• Verified date: January 2018
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Subjects are being asked to participate in this study because they have an arm or leg amputation and have developed pain related to a neuroma (an ongoing localized pain related to a cut nerve ending).

We are studying two different types of surgery to treat the neuroma pain. Today there are many surgical options reported which often means that there is no one best treatment. The surgery that shows the best success so far, involves cutting out the scarred nerve ending (neuroma) and burying the freshly cut nerve ending in a nearby muscle. Recently, a new surgery has been developed called targeted reinnervation (TR). This surgery connects these cut nerve endings to nerves going into nearby nonfunctional muscles. This surgery was developed to allow amputees to have better prosthesis control. By chance, neuroma pain improved significantly with TR. We, therefore, are conducting this clinical trial to evaluate which of these two surgeries best treats neuroma pain. We will ask all participants to fill out a questionnaire both before and after surgery. This will help us understand how a neuroma affects the quality of life of amputees and will allow us to understand which surgery leads to the best improvement in neuroma pain.

In order to confirm the presence and location of the neuroma before surgery, a magnetic resonance image (MRI) will be performed. Taking these pictures requires subjects to lie still for a short period of time but does not involve any invasive procedures. After surgery, the MRI will be done again, this time to see if the nerve shows signs of scarring.

Description:

Loss of an arm or leg is a significant injury that affects a person's job prospects, personal relationships, and overall quality of life. Approximately 25% of all amputees will develop chronic local pain in the remaining part of their amputated limb. This pain is caused by neuromas- disorganized nerve endings and scar tissue that form when an injured nerve tries to heal. Every cut nerve will develop a neuroma unless the two ends of the nerve can be rejoined. With limb amputation, the nerves are cut and one end is lost with the limb, preventing the nerve from repairing itself. Instead, the cut nerve ending forms a painful neuroma. Chronic pain from neuromas is a major reason that amputees cannot wear or use their prostheses comfortably and increases their disability. The current standard surgical treatment for a neuroma is to cut if off and bury the nerve ending in a muscle, to provide cushioning when the neuroma grows back. Even though this is the best current treatment, it is not always successful.

Even when a limb is amputated, the nerves that used to control that limb still carry messages from the brain. Those messages are intended to tell the muscles how or when to move the missing limb, but after amputation, these limb-control nerves are no longer connected to muscles. In 2002, researchers at Northwestern Memorial Hospital in conjunction with the Rehabilitation Institute of Chicago developed a new type of surgery called targeted muscle reinnervation (TMR). In TMR, limb-control nerves are transferred so that they can control new target muscles. The neuromas from the limb-control nerves are removed, then the small nerve that controls the target muscle is cut. The two nerves are joined together so that the limb-control nerve can then grow into, or reinnervate the target muscle. After TMR, when the person tries to move the missing limb, the target muscle contracts instead and these signals can be detected and used to control a prosthesis. TMR has now been done successfully almost 100 times worldwide. Interestingly, almost all of the patients who had painful neuromas before TMR had no neuroma pain after surgery. This result was investigated in laboratory studies - both rat and rabbit amputee neuromas were "cured" with TMR. We think that giving the cut nerve endings somewhere to go and something to do prevents a neuroma from forming.

We plan to compare TMR versus the current standard surgical treatment for painful neuromas. We will measure the effectiveness of both surgeries using an internet-based amputee pain questionnaire. We will also use magnetic resolution imaging (MRI) to look at the nerves before and after surgery. We have received a grant to complete a 4 year study in four hospitals across the US, in around 200 patients, making this the largest neuroma study ever performed. We expect that TMR will be significantly more effective for neuroma pain than the standard treatment. This will change how patients with neuroma pain are treated and help thousands of patients with amputations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 1, 2018
• Est. primary completion date: January 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult, 18 years or older: the Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire is not validated for pain-related evaluation in minors

• An upper limb amputation above the wrist with or without a residual limb or a lower limb amputation above the ankle with a residual limb (individuals with a hip disarticulation amputation lack suitable target muscles for TR)

• A neuroma within the residual limb: defined as patient-reported chronic localized pain consistent with a physical exam that demonstrates that the pain is related to a cut nerve and excludes other causes. There must be a supporting Tinel's sign on physical exam, MRI findings suggestive of a neuroma, or localization of a neuroma by prior intervention (surgical or otherwise) to distinguish the pain from phantom limb pain or cold intolerance that are nonspecific signs of nerve damage that would not be affected by treatment of a neuroma.

• English or Spanish speaking: the PROMIS questionnaire is available in English and parts are currently available in Spanish. The portions that are currently unavailable in Spanish will be translated into Spanish for the purposes of this study.

Exclusion Criteria:

• Prior TR Surgery: these patients have already had a procedure to improve their prosthetic function and in these cases the nerves have been shortened. To perform a second TR procedure with the previously shortened nerves would require a significant proximal dissection and potentially greater soft tissue morbidity than the standard treatment.

• Cognitive impairment, due to TBI or other causes, sufficient to adversely affect understanding of or compliance with study requirements, ability to respond to questionnaires, or ability to give informed consent: The ability to understand and comply with requirements of the study is essential in order for the study to generate useable, reliable data. The ability to obtain relevant feedback through questionnaires is essential to this study.

• Pre-operative assessment that precludes the patient from being eligible for TR or control surgery due to technical surgical concerns.

• Significant other comorbidity: Any other medical issues or injuries that would preclude safe administration of anesthesia or surgical intervention.

• Participation in other ongoing studies related to neuropathic pain.

Related Conditions & MeSH terms

• Neuroma
• Neuroma Amputation
• Pain

Intervention

Procedure:
• Targeted Muscle Reinnervation

• Traction Neurectomy

Locations

Country	Name	City	State
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	San Antonio Military Medical Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in pain of the amputated limb after surgery	Difference in patient-reported pain scores before and after surgical treatment using the online survey tool.; Compare patient-reported pre-operative survey results to those after surgical intervention at intervals over time (1 month, 3 months,6 months, 9 months,1 year, and then every six months thereafter until the conclusion of the study).	12 months
Secondary	Improvement in physical functioning, including prosthesis wear, after surgery	Using the same PROMIS platform, general health, physical functioning (including functional prosthesis wear), and satisfaction following surgery will also be assessed as important secondary outcomes, resulting in a more comprehensive and objective understanding of the effects of the two surgical approaches on neuroma pain.; Another particularly useful tool for this study is the Orthotics and Prosthetics User Survey (OPUS) Functional Status. The OPUS is a validated instrument that assesses how well patients are using their prostheses. Thus, we will examine a very important secondary measure of neuroma pain—the ability to use a prosthesis. Prosthesis use is often the primary problem for individuals with painful neuromas; they hurt most during walking with a prosthesis or when wearing a prosthetic arm. Thus we expect OPUS to be a useful additional measure for quantifying the outcomes of the two types of neuroma surgeries	12 months
Secondary	Using MRI as a tool to determine if targeted muscle reinnervation prevents neuroma recurrence	In our study, pre- and post-operative neuroma size (at one year) will be quantified using MRI scans. Pre-operative MRI measurements will be compared to the removed neuroma specimen to verify the accuracy of the modality. Post-operative MRI measurements will be used to assess whether a neuroma recurred at the site of the surgery and to determine the size of any new lesion.	1 year