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Treating Phantom Limb Pain Using Continuous Peripheral Nerve Blocks: A Department of Defense Funded Multicenter Study (DoD-PLP-Tx)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of California, San Diego
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Brian M. Ilfeld, MD, MS, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01824082
First received: March 30, 2013
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

When a limb is traumatically severed, pain perceived in the part of the body that no longer exists often develops. This is called "phantom limb" pain, and is different from "stump" pain, which is pain within the part of the limb that remains intact. Unfortunately, phantom pain resolves in only 16% of people, with the rest experiencing this pain for the remainder of the lives. There is currently no reliable treatment for phantom limb pain.

The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut—as happens with a traumatic amputation—changes occur in the brain and spinal cord that actually worsen with increasing phantom pain. These abnormal changes may often be corrected by putting local anesthetic—termed a "peripheral nerve block"—on the injured nerve, keeping any "bad signals" from reaching the brain, with resolution of the phantom limb pain. However, when the nerve block ends after a few hours, the phantom pain returns. But, this demonstrates that the brain abnormalities—and phantom pain—that occur with an amputation may be dependent upon the "bad" signals being sent from the injured nerve(s), suggesting that a very long peripheral nerve block—lasting many days rather than hours—may permanently reverse the abnormal changes in the brain, and provide lasting relief from phantom pain.

Until recently, extending a peripheral nerve block beyond 16 hours was unrealistic. However, a treatment option called a "continuous peripheral nerve block" is now available. This technique involves the placement of a tiny tube—smaller than a piece of spaghetti—through the skin and next to the nerves supplying the amputated limb. The tiny tube may be placed with minimal discomfort in about 15 minutes. Numbing medicine called local anesthetic is then infused through the tube, blocking any signals that the injured nerve sends to the spinal cord and brain. Using a small, portable infusion pump, this prolonged nerve block may be provided in individuals' own homes.

The ultimate objective of the proposed research study is to determine if a 6-day continuous peripheral nerve block provided at home is an effective treatment for persistent phantom limb pain following a traumatic limb amputation. The primary hypothesis (what the researchers predict) is that phantom limb pain intensity will be significantly decreased 4 weeks following treatment with a 6-day continuous peripheral nerve block.


Condition Intervention Phase
Phantom Limb Pain
Drug: Perineural infusion [continuous peripheral nerve block(s)]
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous Peripheral Nerve Blocks

Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Phantom limb pain intensity 4 weeks following initiation of an ambulatory CPNB (as measured by the Numeric Rating Scale within the Brief Pain Inventory). [ Time Frame: 4 weeks post-intervention ] [ Designated as safety issue: No ]
    Current/present, worst, least, and average phantom pain will be assessed using a Numeric Rating Scale (NRS) as part of the Brief Pain Inventory (short form), with the "average" pain score designated as the primary endpoint. In addition, average and worst residual limb pain NRS will be recorded separately from the phantom pain scores. The NRS is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, with zero equivalent to no pain and 10 equivalent to the worst imaginable pain.


Secondary Outcome Measures:
  • Perception of well-being 4 weeks following an ambulatory CPNB (as measured with the Patient Global Impression of Change Scale). [ Time Frame: 4 weeks post-intervention. ] [ Designated as safety issue: No ]
    The Patient Global Impression of Change Scale is a 7-point ordinal scale requiring the subject to rate the current severity of their global situation as it relates to phantom limb pain (as defined by each individual) compared to their baseline. This scale has the words "very much worse" to the left by the number one, and "very much improved" to the right, adjacent to the number seven. The words "no change" are in the middle of the scale above the number four. The Patient Global Impression of Change Scale has been validated in over ten prospective trials, including studies specifically involving peripheral neuropathy.

  • Physical and emotional functioning 4 weeks following initiation of an ambulatory CPNB (as measured with the Brief Pain Inventory). [ Time Frame: 4 weeks following initiation of CPNB ] [ Designated as safety issue: No ]
    The Brief Pain Inventory is an instrument that includes—in addition to pain intensity scales—seven measures evaluating pain's interference with physical and emotional functioning, such as sleep, relations with others, and enjoyment of life. has been used in countless clinical studies of chronic pain,and validated specifically in neuropathic pain states. This instrument is associated with minimal subject burden and is easily interpreted by patients of all ages and education levels.It has high test-retest reliability and correlates well with much longer questionnaires, including the McGill measures and EuroQol.

  • Depression 4 weeks following initiation of an ambulatory CPNB (as measured with the Beck Depression Inventory). [ Time Frame: 4 weeks following initiation of CPNB ] [ Designated as safety issue: No ]
    The Beck Depression Inventory is a 21-item instrument that measures characteristic symptoms and signs of depression, requires only a 5th grade comprehension level to adequately understand the questions, and demonstrates a high internal consistency (0.73-0.92, mean of 0.86), reliability and validity. Each of the 21 factors is rated on a 0-3 scale, and then summed to produce the total score of 0-63. Mild, moderate, and severe depression is defined with scores of 10-18, 19-29, and 30-63, respectively.


Other Outcome Measures:
  • Physical and emotional functioning as measured with the Brief Pain Inventory. [ Time Frame: 1, 7, 14, 21 days and 6 and 12 months following initiation of CPNB ] [ Designated as safety issue: No ]
    The Brief Pain Inventory is an instrument that includes—in addition to pain intensity scales—seven measures evaluating pain's interference with physical and emotional functioning, such as sleep, relations with others, and enjoyment of life. has been used in countless clinical studies of chronic pain,and validated specifically in neuropathic pain states. This instrument is associated with minimal subject burden and is easily interpreted by patients of all ages and education levels.It has high test-retest reliability and correlates well with much longer questionnaires, including the McGill measures and EuroQol.

  • Depression as measured with the Beck's Depression Inventory [ Time Frame: 6 and 12 months following initiation of CPNB ] [ Designated as safety issue: No ]
    The Beck Depression Inventory is a 21-item instrument that measures characteristic symptoms and signs of depression, requires only a 5th grade comprehension level to adequately understand the questions, and demonstrates a high internal consistency (0.73-0.92, mean of 0.86), reliability and validity. Each of the 21 factors is rated on a 0-3 scale, and then summed to produce the total score of 0-63. Mild, moderate, and severe depression is defined with scores of 10-18, 19-29, and 30-63, respectively.

  • Frequency and average duration of phantom and residual limb pain [ Time Frame: 1, 28 days and 6 and 12 months following initiation of CPNB ] [ Designated as safety issue: No ]
    Frequency measured in average number events/day over previous 3 days; duration measured as average number of hours/minutes each episode lasted.

  • Perception of well-being (as measured with the Patient Global Impression of Change Scale). [ Time Frame: 1, 7 days and 6, 12 months following initiation of CPNB ] [ Designated as safety issue: No ]
    The Patient Global Impression of Change Scale is a 7-point ordinal scale requiring the subject to rate the current severity of their global situation as it relates to phantom limb pain (as defined by each individual) compared to their baseline. This scale has the words "very much worse" to the left by the number one, and "very much improved" to the right, adjacent to the number seven. The words "no change" are in the middle of the scale above the number four. The Patient Global Impression of Change Scale has been validated in over ten prospective trials, including studies specifically involving peripheral neuropathy.

  • Masking assessment [ Time Frame: 28 days following the initial and (if applicable) crossover initiation of CPNB ] [ Designated as safety issue: No ]

    Which study fluid do you believe you received during your most-recent infusion:

    ☐Definitely active ☐Probably active ☐Don't know ☐ Probably saline ☐ Definitely saline



Estimated Enrollment: 180
Study Start Date: December 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ropivacaine 0.5%
Electronic, programmable, portable infusion pumps will be used to administer perineural study solution at fixed rates for over 6 days. Subjects will receive a total of 1,100 mL of study fluid from either one (upper extremity) or two (lower extremity) pump and external reservoir combinations. The continuous basal infusion rate will be determined by catheter location: femoral 2.5 mL/h; popliteal-sciatic 5 mL/h; and infraclavicular 7.5 mL/h (37.5 mg/h for both upper and lower extremity subjects). No patient-controlled bolus dose will be included. Subjects assigned this treatment for their initial infusion will have the option of returning 4-16 weeks later for a second infusion of the alternate treatment: normal saline.
Drug: Perineural infusion [continuous peripheral nerve block(s)]
Electronic, programmable, portable infusion pumps will be used to administer perineural study solution at fixed rates for over 6 days. Subjects will receive a total of 1,100 mL of study fluid from either one (upper extremity) or two (lower extremity) pump and external reservoir combinations. The continuous basal infusion rate will be determined by catheter location: femoral 2.5 mL/h; popliteal-sciatic 5 mL/h; and infraclavicular 7.5 mL/h (37.5 mg/h for both upper and lower extremity subjects). No patient-controlled bolus dose will be included. Subjects will have the option of returning 4-16 weeks later for a second infusion of the alternate treatment solution.
Placebo Comparator: Normal saline (salt water) infusion
Electronic, programmable, portable infusion pumps will be used to administer perineural study solution at fixed rates for over 6 days. Subjects will receive a total of 1,100 mL of normal saline placebo fluid from either one (upper extremity) or two (lower extremity) pump and external reservoir combinations. The continuous basal infusion rate will be determined by catheter location: femoral 2.5 mL/h; popliteal-sciatic 5 mL/h; and infraclavicular 7.5 mL/h (37.5 mg/h for both upper and lower extremity subjects). No patient-controlled bolus dose will be included. Subjects assigned this treatment for their initial infusion will have the option of returning 4-16 weeks later for a second infusion of the alternate treatment: ropivacaine 0.5%.
Drug: Perineural infusion [continuous peripheral nerve block(s)]
Electronic, programmable, portable infusion pumps will be used to administer perineural study solution at fixed rates for over 6 days. Subjects will receive a total of 1,100 mL of study fluid from either one (upper extremity) or two (lower extremity) pump and external reservoir combinations. The continuous basal infusion rate will be determined by catheter location: femoral 2.5 mL/h; popliteal-sciatic 5 mL/h; and infraclavicular 7.5 mL/h (37.5 mg/h for both upper and lower extremity subjects). No patient-controlled bolus dose will be included. Subjects will have the option of returning 4-16 weeks later for a second infusion of the alternate treatment solution.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Upper or lower limb traumatic or surgical amputation at least 12 weeks prior to enrollment at or distal to the mid-humerus or hip (femoral head remaining), respectively; and including at least one metacarpal or metatarsal bone, respectively.
  • Experiencing at least moderate phantom limb pain (defined as 2 or higher on the numeric rating scale, NRS 0-10), at least three times each week for the previous 8 weeks.
  • Accepting of an ambulatory continuous peripheral nerve block for 6 days.
  • Willing to avoid changes to their analgesic regimen from 4 weeks prior to and at least 4 weeks following the initial catheter placement (preferably 4 weeks following the second/crossover catheter insertion as well).
  • Having a "caretaker" who will transport the subject home following the catheter insertion(s), and remain with the subject for the first night of the infusions.

Exclusion Criteria:

  • Known renal insufficiency
  • Allergy to study medications
  • Pregnancy
  • Incarceration
  • Inability to communicate with the investigators
  • Morbid obesity (BMI greater than 40)
  • Comorbidity that results in moderate-to-severe functional limitation (ASA greater than 2)
  • Possessing any contraindication to ambulatory perineural catheter placement or perineural local anesthetic infusion:

    • Current infection
    • Immune-compromised status of any etiology
    • Uncontrolled anxiety/panic disorder
    • Inability to contact investigators during the perineural infusion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01824082

Contacts
Contact: Anya C Morgan, MA 858-242-6017 acmorgan@ucsd.edu

Locations
United States, California
Veteran's Affairs Palo Alto Health Care System Recruiting
Palo Alto, California, United States, 94304
Sub-Investigator: Edward Mariano, MD, MAS         
Naval Medical Center San Diego Not yet recruiting
San Diego, California, United States, 92134
Sub-Investigator: Steven Hanling, MD         
University of California, San Diego, Hillcrest Medical Center Recruiting
San Diego, California, United States, 92103
Sub-Investigator: Sarah Madison, MD         
United States, Maryland
Walter Reed Army National Medical Center Recruiting
Bethesda, Maryland, United States, 20889
Sub-Investigator: Michael Kent, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Sub-Investigator: Alparslan Turan, MD         
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Brian M Ilfeld, MD, MS University of California, San Diego
  More Information

No publications provided

Responsible Party: Brian M. Ilfeld, MD, MS, Professor of Anesthesiology, In Residence, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01824082     History of Changes
Other Study ID Numbers: Phantom Pain Treatment (DoD)
Study First Received: March 30, 2013
Last Updated: October 28, 2014
Health Authority: United States: Department of Defense

Keywords provided by University of California, San Diego:
phantom pain
traumatic limb amputation
amputees

Additional relevant MeSH terms:
Phantom Limb
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Pain
Pain, Postoperative
Pathologic Processes
Perceptual Disorders
Postoperative Complications
Signs and Symptoms

ClinicalTrials.gov processed this record on November 24, 2014