Phantom Limb PainPhase 4DoD-PLP-TxNCT01824082
Treating Phantom Limb Pain Using Continuous Peripheral Nerve Blocks: A Department of Defense Funded Multicenter Study
A Phase 4 study testing Perineural infusion [continuous peripheral nerve block(s)] in people with Phantom Limb Pain, run by University of California, San Diego at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Phantom Limb Pain
- What is being tested?
- Perineural infusion [continuous peripheral nerve block(s)]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Dec 2013to Oct 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Known renal insufficiency
- Allergy to study medications
- Pregnancy
- Incarceration
- Inability to communicate with the investigators
- Morbid obesity (BMI greater than 40)
Show all 12Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Walter Reed Army National Medical Center
Bethesda, Maryland, 20889
Cleveland Clinic
Cleveland, Ohio, 44195
Veteran's Affairs Palo Alto Health Care System
Palo Alto, California, 94304
University of California, San Diego, Hillcrest Medical Center
San Diego, California, 92103
About this study
Official title: Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous Peripheral Nerve Blocks
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.
Read more
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.
Read the detailed description
Background. The combination of increased munitions force, use of improvised explosive devices, and casualty survival rates has resulted in a dramatic increase in the percentage of injured combat veterans living with a traumatic amputation. Of American Veteran amputees, 35-98% develop chronic, intractable pain perceived as being from the missing limb, a phenomenon termed "phantom limb pain." This pain resolves in only 16% of afflicted individuals, and there is currently no reliable treatment. The etiology of phantom pain remains unclear, but evidence suggests that severing a nerve provokes changes in the spinal cord, thalamus, and cerebral cortex. When neural input from an amputated limb is blocked with local anesthetic (a peripheral nerve block), cortical abnormalities and phantom pain frequently resolve. However, when the single-injection nerve block resolves after a few hours, the phantom pain returns. These findings demonstrate that cortical abnormalities and phantom pain may be maintained from abnormal peripheral input, suggesting that a peripheral nerve block of extended duration-lasting many days rather than hours-may permanently reorganize cortical pain mapping, thus providing lasting relief from phantom pain. A "continuous peripheral nerve block" (CPNB) involves the percutaneous insertion of a catheter directly adjacent to the peripheral nerves supplying an affected limb. Local anesthetic infused via the catheter(s) induces a completely insensate extremity for as long as desired without any systemic side effects. Additionally, CPNB may be provided on an ambulatory basis using a small, portable pump to infuse the local anesthetic.
Objective. To determine if ambulatory CPNB is an effective treatment for intractable phantom limb pain following a traumatic limb amputation. Previously-published small, uncontrolled series describe patients immediately following surgical amputation whose phantom limb pain dramatically decreased or completely resolved with CPNB. We have data from a randomized, double-masked, placebo-controlled, crossover pilot study suggesting great promise treating intractable phantom limb pain with ambulatory CPNB: participants (n=3) experienced no change in their phantom pain following a 6-day infusion of normal saline; however, with a 6-day CPNB of potent local anesthetic administered 4 months later, subjects (n=2; one patient returned to duty before crossover infusion) experienced complete resolution of their phantom limb pain. Within the 12-week follow-up period, one subject experienced no phantom pain recurrence; and the other subject reported mild pain occurring once each week of just a small fraction of his original pain.
Specific Aims. The primary hypothesis is that phantom limb pain intensity will be significantly decreased 4 weeks following an ambulatory CPNB (as measured by the Numeric Rating Scale of the Brief Pain Inventory).
Study Design. We propose a multicenter, randomized, double-masked, placebo-controlled, simultaneous parallel and crossover, human-subjects clinical trial. We will include subjects with an existing upper or lower amputation who experience phantom limb pain at least daily for the previous 4 weeks. Catheter site(s) will be determined by amputation location. Subjects will be randomized to receive one of two study solutions in a double-masked manner: either a local anesthetic (ropivacaine 0.5%) or placebo (normal saline). Catheters will be removed after 6 days of at-home infusion. Although not required, each subject has the option to return for the alternative treatment four weeks later (crossover infusion). The primary endpoint will be the difference in average phantom pain intensity at baseline and 4 weeks following the initial infusion as measured with the Numeric Rating Scale between treatment groups for the initial infusion. Major secondary endpoints will involve intra- and inter-subject comparisons of additional measures of pain and health-related quality-of-life.
Clinical Impact. From 2001-2006, over 70% of all U.S. military casualties endured a major limb injury, with an amputation rate of 28% within Operation Enduring Freedom alone. Previous conflicts have left tens-of-thousands of United States Armed Forces Veterans with missing limbs. CPNB are now relatively ubiquitous within the United States, but applied nearly exclusively to provide acute post-injury/surgical analgesia. If the proposed study demonstrates that ambulatory CPNB is a reliable treatment for intractable phantom limb pain, the resulting impact in treating the consequences of traumatic amputation will be immediate and profound, as healthcare providers within the United States Armed Forces and Veterans Affairs Medical Centers already have expertise placing and managing perineural catheters. Currently, CPNB is provided exclusively in the acute setting-to treat pain immediately following a battlefield injury or surgery-and not chronic, intractable phantom limb pain. However, because there is little technical difference in providing CPNB for acute versus chronic pain, the thousands of U.S. Veterans and active duty personnel suffering from intractable phantom pain could be treated relatively easily, rapidly, and with negligible additional costs.
- Conditions
- Phantom Limb Pain
- Being tested
- Perineural infusion [continuous peripheral nerve block(s)]
- Keywords
- phantom pain, traumatic limb amputation, amputees
- Medical subject headings
- Phantom Limb
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Perineural infusion [continuous peripheral nerve block(s)]Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Ropivacaine 0.5% | Experimental | 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. Receives: Drug: Perineural infusion [continuous peripheral nerve block(s)] |
| Normal saline (salt water) infusion | Placebo comparator | 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%. Receives: Drug: Perineural infusion [continuous peripheral nerve block(s)] |
What is being measured
The primary outcome is the main question the study is designed to answer.
"Average" Phantom Limb Pain Intensity 4 Weeks Following Initiation of an Ambulatory Continuous Peripheral Nerve Block (as Measured by the Numeric Rating Scale Within the Brief Pain Inventory)
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. These data are 4 weeks after the initiation of the FIRST intervention (and not the optional crossover treatment).
Measured: 4 weeks following the initiation of the initial intervention.
Secondary outcomes (3)
Perception of Well-being (as Measured With the Patient Global Impression of Change Scale).
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. These data are from 4 weeks after the initiation of the FIRST intervention (and not the optional crossover treatment).
Measured: 4 weeks following the initiation of the initial intervention
Physical and Emotional Functioning 4 Weeks Following Initiation of Intervention (as Measured With the Brief Pain Inventory Interference Domain).
The Brief Pain Inventory (interference sub scale) is an instrument that measures the interference with physical and emotional functioning using a 0-10 scale (0 = no interference; 10 = complete interference). The seven interference questions involve general activity, mood, walking ability, normal work activities (both inside and outside of the home), relationships, sleep, and enjoyment of life. The seven functioning questions can be added to produce an interference subscale (0-70). The use of both single items (e.g., mood) and the composite scores is supported. These data are from 4 weeks after the initiation of the FIRST intervention (and not the optional crossover treatment).
Measured: 4 weeks following initiation of the initial intervention
Depression 4 Weeks Following Initiation of Intervention (as Measured With the Beck Depression Inventory).
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. This data is 4 weeks following the initiation of the initial intervention, and NOT the optional crossover treatment.
Measured: 4 weeks following initiation of the initial intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study start1 Dec 2013
- Primary completionNov 2019
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Phantom Limb PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Brian M. Ilfeld, MD, MS, University of California, San Diego
- Investigators
- Brian M Ilfeld, MD, MS, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01824082
- Sponsor's protocol ID
- Phantom Pain Treatment (DoD)
- Acronym
- DoD-PLP-Tx
- Status last verified
- May 2024
- First submitted
- 30 Mar 2013
- Last updated
- 8 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ilfeld BM, Khatibi B, Maheshwari K, Madison S, Ali Sakr Esa W, Mariano ER, Kent M, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha E, Li S, Turan A; PAINfRE Investigators. Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial. Reg Anesth Pain Med. 2023 Sep;48(9):471-477. doi: 10.1136/rapm-2023-104389. Epub 2023 Mar 9.
PubMed 36894197Ilfeld BM, Khatibi B, Maheshwari K, Madison SJ, Ali Sakr Esa W, Mariano ER, Kent ML, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha EJ, Yang D, Padwal JA, Turan A; PAINfRE Investigators. Immediate Effects of a Continuous Peripheral Nerve Block on Postamputation Phantom and Residual Limb Pain: Secondary Outcomes From a Multicenter Randomized Controlled Clinical Trial. Anesth Analg. 2021 Oct 1;133(4):1019-1027. doi: 10.1213/ANE.0000000000005673.
PubMed 34314392Ilfeld BM, Khatibi B, Maheshwari K, Madison SJ, Esa WAS, Mariano ER, Kent ML, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha EJ, Ma C, Padwal JA, Turan A; PAINfRE Investigators. Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial. Pain. 2021 Mar 1;162(3):938-955. doi: 10.1097/j.pain.0000000000002087.
PubMed 33021563
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treating Intractable Post-Amputation Phantom Limb Pain With Ambulatory Continuous Peripheral Nerve Blocks
- ClinicalTrials.gov ID
- NCT01824082
- Acronym / sponsor ID
- DoD-PLP-Tx / Phantom Pain Treatment (DoD)
- Conditions
- Phantom Limb Pain
- Keywords
- phantom pain, traumatic limb amputation, amputees
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 1 Dec 2013 (actual)
- Primary completion
- Nov 2019 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 4 Apr 2013 (estimated)
- Results
- Posted 29 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background. The combination of increased munitions force, use of improvised explosive devices, and casualty survival rates has resulted in a dramatic increase in the percentage of injured combat veterans living with a traumatic amputation. Of American Veteran amputees, 35-98% develop chronic, intractable pain perceived as being from the missing limb, a phenomenon termed "phantom limb pain." This pain resolves in only 16% of afflicted individuals, and there is currently no reliable treatment. The etiology of phantom pain remains unclear, but evidence suggests that severing a nerve provokes changes in the spinal cord, thalamus, and cerebral cortex. When neural input from an amputated limb is blocked with local anesthetic (a peripheral nerve block), cortical abnormalities and phantom pain frequently resolve. However, when the single-injection nerve block resolves after a few hours, the phantom pain returns. These findings demonstrate that cortical abnormalities and phantom pain may be maintained from abnormal peripheral input, suggesting that a peripheral nerve block of extended duration-lasting many days rather than hours-may permanently reorganize cortical pain mapping, thus providing lasting relief from phantom pain. A "continuous peripheral nerve block" (CPNB) involves the percutaneous insertion of a catheter directly adjacent to the peripheral nerves supplying an affected limb. Local anesthetic infused via the catheter(s) induces a completely insensate extremity for as long as desired without any systemic side effects. Additionally, CPNB may be provided on an ambulatory basis using a small, portable pump to infuse the local anesthetic.
Objective. To determine if ambulatory CPNB is an effective treatment for intractable phantom limb pain following a traumatic limb amputation. Previously-published small, uncontrolled series describe patients immediately following surgical amputation whose phantom limb pain dramatically decreased or completely resolved with CPNB. We have data from a randomized, double-masked, placebo-controlled, crossover pilot study suggesting great promise treating intractable phantom limb pain with ambulatory CPNB: participants (n=3) experienced no change in their phantom pain following a 6-day infusion of normal saline; however, with a 6-day CPNB of potent local anesthetic administered 4 months later, subjects (n=2; one patient returned to duty before crossover infusion) experienced complete resolution of their phantom limb pain. Within the 12-week follow-up period, one subject experienced no phantom pain recurrence; and the other subject reported mild pain occurring once each week of just a small fraction of his original pain.
Specific Aims. The primary hypothesis is that phantom limb pain intensity will be significantly decreased 4 weeks following an ambulatory CPNB (as measured by the Numeric Rating Scale of the Brief Pain Inventory).
Study Design. We propose a multicenter, randomized, double-masked, placebo-controlled, simultaneous parallel and crossover, human-subjects clinical trial. We will include subjects with an existing upper or lower amputation who experience phantom limb pain at least daily for the previous 4 weeks. Catheter site(s) will be determined by amputation location. Subjects will be randomized to receive one of two study solutions in a double-masked manner: either a local anesthetic (ropivacaine 0.5%) or placebo (normal saline). Catheters will be removed after 6 days of at-home infusion. Although not required, each subject has the option to return for the alternative treatment four weeks later (crossover infusion). The primary endpoint will be the difference in average phantom pain intensity at baseline and 4 weeks following the initial infusion as measured with the Numeric Rating Scale between treatment groups for the initial infusion. Major secondary endpoints will involve intra- and inter-subject comparisons of additional measures of pain and health-related quality-of-life.
Clinical Impact. From 2001-2006, over 70% of all U.S. military casualties endured a major limb injury, with an amputation rate of 28% within Operation Enduring Freedom alone. Previous conflicts have left tens-of-thousands of United States Armed Forces Veterans with missing limbs. CPNB are now relatively ubiquitous within the United States, but applied nearly exclusively to provide acute post-injury/surgical analgesia. If the proposed study demonstrates that ambulatory CPNB is a reliable treatment for intractable phantom limb pain, the resulting impact in treating the consequences of traumatic amputation will be immediate and profound, as healthcare providers within the United States Armed Forces and Veterans Affairs Medical Centers already have expertise placing and managing perineural catheters. Currently, CPNB is provided exclusively in the acute setting-to treat pain immediately following a battlefield injury or surgery-and not chronic, intractable phantom limb pain. However, because there is little technical difference in providing CPNB for acute versus chronic pain, the thousands of U.S. Veterans and active duty personnel suffering from intractable phantom pain could be treated relatively easily, rapidly, and with negligible additional costs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ropivacaine 0.5% | Experimental | 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 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. |
| Normal saline (salt water) infusion | Placebo comparator | 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 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%. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (12 listed)
- Known renal insufficiency
- Allergy to study medications
- Pregnancy
- Incarceration
- Inability to communicate with the investigators
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Normal saline (salt water) infusion, Ropivacaine 0.5% |
Primary outcome
"Average" Phantom Limb Pain Intensity 4 Weeks Following Initiation of an Ambulatory Continuous Peripheral Nerve Block (as Measured by the Numeric Rating Scale Within the Brief Pain Inventory)
Time frame: 4 weeks following the initiation of the initial intervention.
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. These data are 4 weeks after the initiation of the FIRST intervention (and not the optional crossover treatment).
3 secondary outcomes
Perception of Well-being (as Measured With the Patient Global Impression of Change Scale).
Time frame: 4 weeks following the initiation of the initial intervention
Physical and Emotional Functioning 4 Weeks Following Initiation of Intervention (as Measured With the Brief Pain Inventory Interference Domain).
Time frame: 4 weeks following initiation of the initial intervention
Depression 4 Weeks Following Initiation of Intervention (as Measured With the Beck Depression Inventory).
Time frame: 4 weeks following initiation of the initial intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36894197Ilfeld BM, Khatibi B, Maheshwari K, Madison S, Ali Sakr Esa W, Mariano ER, Kent M, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha E, Li S, Turan A; PAINfRE Investigators. Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial. Reg Anesth Pain Med. 2023 Sep;48(9):471-477. doi: 10.1136/rapm-2023-104389. Epub 2023 Mar 9.
- Derived from this study: PubMed 34314392Ilfeld BM, Khatibi B, Maheshwari K, Madison SJ, Ali Sakr Esa W, Mariano ER, Kent ML, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha EJ, Yang D, Padwal JA, Turan A; PAINfRE Investigators. Immediate Effects of a Continuous Peripheral Nerve Block on Postamputation Phantom and Residual Limb Pain: Secondary Outcomes From a Multicenter Randomized Controlled Clinical Trial. Anesth Analg. 2021 Oct 1;133(4):1019-1027. doi: 10.1213/ANE.0000000000005673.
- Derived from this study: PubMed 33021563Ilfeld BM, Khatibi B, Maheshwari K, Madison SJ, Esa WAS, Mariano ER, Kent ML, Hanling S, Sessler DI, Eisenach JC, Cohen SP, Mascha EJ, Ma C, Padwal JA, Turan A; PAINfRE Investigators. Ambulatory continuous peripheral nerve blocks to treat postamputation phantom limb pain: a multicenter, randomized, quadruple-masked, placebo-controlled clinical trial. Pain. 2021 Mar 1;162(3):938-955. doi: 10.1097/j.pain.0000000000002087.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian M Ilfeld, MD, MS principal investigator
University of California, San Diego
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Perineural infusion [continuous peripheral nerve block(s)] in people with Phantom Limb Pain, run by University of California, San Diego at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"Average" Phantom Limb Pain Intensity 4 Weeks Following Initiation of an Ambulatory Continuous Peripheral Nerve Block (as Measured by the Numeric Rating Scale Within the Brief Pain Inventory) (time frame: 4 weeks following the initiation of the initial intervention.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01824082, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.