Treating Phantom Limb Pain Using Continuous Peripheral Nerve Blocks: A Department of Defense Funded Multicenter Study

NCT01824082 | Completed Phase 4 Results DMC

• 1 other identifier: Phantom Pain Treatment (DoD)
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Phantom Limb Pain

Keywords

phantom pain; traumatic limb amputation; amputees

Outcome Measures

Primary Outcomes (1)

• "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).

  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).

  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).

  4 weeks following initiation of the initial intervention

• Depression 4 Weeks Following Initiation of Intervention (as Measured With the Beck Depression Inventory).

  4 weeks following initiation of the initial intervention

Other Outcomes (16)

• Change in Physical and Emotional Functioning at 6 and 12 Months Compared With Baseline (as Measured With the Brief Pain Inventory Interference Domain).

  6 and 12 months following initiation of the initial intervention

• Change in Depression 6 and 12 Months Compared With Baseline (as Measured With the Beck Depression Inventory).

  6 and 12 months following initiation of the initial intervention

• Perception of Well-being (as Measured With the Patient Global Impression of Change Scale).

  6 and 12 months following initiation of intervention

Study Arms (2)

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.

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%.

Drug: Perineural infusion [continuous peripheral nerve block(s)]

Interventions

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.

Normal saline (salt water) infusion; Ropivacaine 0.5%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• United States Department of Defense: collaborator

Study Sites (4)

Veteran's Affairs Palo Alto Health Care System

Palo Alto, California, 94304, United States

Location

University of California, San Diego, Hillcrest Medical Center

San Diego, California, 92103, United States

Location

Walter Reed Army National Medical Center

Bethesda, Maryland, 20889, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (3)

• 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.

  PMID: 36894197 DERIVED

• Ilfeld 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.

  PMID: 34314392 DERIVED

• Ilfeld 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.

  PMID: 33021563 DERIVED

MeSH Terms

Conditions

Phantom Limb

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Results Point of Contact

• Title: Brian M. Ilfeld
• Organization: University of California San Diego

bilfled@health.ucsd.edu

858-822-0776

Study Officials

• Brian M Ilfeld, MD, MS

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigators originally planned to unmask the treatment groups following the completion of the statistical analysis ("triple masked"); but following the analysis using "treatment A" and "treatment B" labels, opted to wait to unmask the groups until the manuscript was drafted ("quadruple masking").
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology, In Residence

Study Record Dates

• First Submitted: March 30, 2013
• First Posted: April 4, 2013
• Study Start: December 1, 2013
• Primary Completion: November 1, 2019
• Study Completion: October 1, 2020
• Last Updated: May 8, 2024
• Results First Posted: April 29, 2021

Record last verified: 2024-05

Locations

US (4)