Improving Postamputation Functioning by Decreasing Phantom Pain With Perioperative Continuous Peripheral Nerve Blocks: A Department of Defense Funded Multicenter Study

• ClinicalTrials.gov Identifier: NCT03461120
• Recruitment Status: Enrolling by invitation
• First Posted: March 9, 2018
• Last Update Posted: April 26, 2019
• Sponsor: University of California, San Diego
• Collaborators: United States Department of Defense; United States Naval Medical Center, San Diego; The Cleveland Clinic; University of Texas MD Anderson; Walter Reed National Military Medical Center; Johns Hopkins University; Wake Forest Medical Center
• Information provided by (Responsible Party): Brian M. Ilfeld, MD, MS, University of California, San Diego

Study Description

Brief Summary:

When a limb is amputated, pain perceived in the part of the body that no longer exists often develops, called "phantom limb" pain. The exact reason that phantom limb pain occurs is unclear, but when a nerve is cut-as happens with an amputation-changes occur in the brain and spinal cord that are associated with persistent pain. The negative feedback-loop between the injured limb and the brain can be stopped by putting local anesthetic-called a "nerve block"-on the injured nerve, effectively keeping any "bad signals" from reaching the brain. A "continuous peripheral nerve block" (CPNB) is a technique providing pain relief that involves inserting a tiny tube-smaller than a piece of spaghetti-through the skin and next to the target nerve. Local anesthetic is then introduced through the tiny tube, which bathes the nerve in the numbing medicine. This provides a multiple-day block that provides opioid-free pain control with no systemic side effects, and may prevent the destructive feedback loop that results in phantom limb pain following an amputation. We propose a multicenter, randomized, triple-masked (investigators, subjects, statisticians), placebo-controlled, parallel arm, human-subjects clinical trial to determine if a prolonged, high-concentration (dense), perioperative CPNB improves post-amputation physical and emotional functioning while decreasing opioid consumption, primarily by preventing chronic phantom limb pain.

Condition or disease	Intervention/treatment	Phase
Lower Extremity Surgical Amputation; Post-amputation Phantom Limb Pain	Drug: Experimental continuous peripheral nerve blocks; Drug: Control continuous peripheral nerve blocks	Phase 4

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Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The only individuals aware of treatment assignment will be the Investigational Drug Service pharmacists who prepare the treatment infusate
• Primary Purpose: Prevention
• Official Title: Improving Postamputation Functioning by Decreasing Phantom Limb Pain and Opioid Use With Perioperative Continuous Peripheral Nerve Blocks: A Multicenter RCT
• Actual Study Start Date: March 23, 2018
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment; Bupivacaine 0.3% infusion for 7 days via femoral and sciatic perineural catheters	Drug: Experimental continuous peripheral nerve blocks; Bupivacaine 0.3% infusions for 7 days via femoral and sciatic perineural catheters; Other Name: Experimental perineural local anesthetic infusion
Control; Bupivacaine 0.1% infusion for 1 day followed by normal saline for a total of 7 days via femoral and sciatic perineural catheters	Drug: Control continuous peripheral nerve blocks; Bupivacaine 0.1% infusions for 1 day followed by normal saline for a total of 7 days via femoral and sciatic perineural catheters; Other Name: Control perineural local anesthetic infusion

Outcome Measures

Primary Outcome Measures :

1. Locomotor Capabilities Index-5 [ Time Frame: Postoperative Month 9 ]
   comprised of 14 items, all scored on a 5-point ordinal scale. Each question inquires about the ability and level of independence when performing a specific activity. There are two subscales comprised of 7 questions each evaluating basic and advanced abilities, but the primary end point of the current study will involve the total score that includes both activity levels.

Secondary Outcome Measures :

1. Locomotor Capabilities Index-5 [ Time Frame: Baseline; Months 6 and 12 ]
   comprised of 14 items, all scored on a 5-point ordinal scale. Each question inquires about the ability and level of independence when performing a specific activity. There are two subscales comprised of 7 questions each evaluating basic and advanced abilities.
2. World Health Organization Disability Assessment Schedule 2.0 [ Time Frame: Baseline, Months 1, 3, 6, 9, and 12 ]
   The instrument was developed by the World Health Organization to focus on those aspects of life most important to patients,99 and is composed of 36 questions assessing functioning in 6 domains: (1) understanding and communication, (2) mobility, (3) self-care, (4) interactions with others, (5) life activities, and (6) participation in community/society. Each of the 36 questions is rated on a 0-4 scale (0: no difficulty; 4: extreme difficulty or cannot do), and then summed to produce both a total score as well as domain-specific scores for more in depth analysis.
3. Beck Depression Inventory [ Time Frame: Baseline and Month 12 ]
   This is a 21-item instrument with each of the factors rated on a 0-3 scale, and then summed to produce the total score of 0-63
4. Phantom limb pain [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   Current/present, worst, least, and average phantom limb pain will be assessed using a Numeric Rating Scale (NRS) included in the Brief Pain Inventory (short form). The NRS is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, zero equivalent to no pain and 10 equivalent to the worst imaginable pain.
5. Residual limb pain [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   Current/present, worst, least, and average residual limb pain will be assessed using a Numeric Rating Scale (NRS) included in the Brief Pain Inventory (short form). The NRS is a highly-sensitive measure of pain intensity with numbers ranging from 0 to 10, zero equivalent to no pain and 10 equivalent to the worst imaginable pain.
6. Opioid consumption [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   All opioids consumed (reported as oral morphine equivalents)
7. Non-painful phantom limb sensations frequency [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   non-painful sensations referred to the lost body part (frequency)
8. Non-painful phantom limb sensations duration [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   non-painful sensations referred to the lost body part (duration)
9. Phantom limb pain frequency [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
   painful sensations referred to the lost body part (frequency)
10. Phantom limb pain average duration [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
    painful sensations referred to the lost body part (average duration)
11. Residual limb pain frequency [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
    painful sensations localized to the portion of limb still physically present (frequency)
12. Residual limb pain duration [ Time Frame: Baseline, postoperative days 1, 2 and 8; Months 1, 3, 6, 9, and 12 ]
    painful sensations localized to the portion of limb still physically present (average duration)
13. Masking assessment [ Time Frame: Postoperative day 8 ]
    Subject's belief of which treatment received reported as: definitely active, probably active, do not know, probably saline, or definitely saline

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• scheduled for a unilateral lower limb amputation distal to the femoral head and including at least one metatarsal bone
• continuous peripheral nerve blocks are planned for perioperative analgesia
• willing to have their perineural infusion extended for a total of 7 days
• willing to undergo ambulatory perineural infusion following hospital discharge

Exclusion Criteria:

• Known hepatic or renal insufficiency
• allergy to any study medication
• pregnancy
• incarceration
• inability to communicate with the investigators
• comorbidity precluding either perineural catheter insertion or subsequent ambulatory perineural infusion (e.g., current infection at the catheter insertion site, immune-compromised status of any etiology)
• weight < 45 kg
• inability to contact the investigators during the perineural infusion, and vice versa (e.g., lack of telephone access)
• investigator opinion that the potential subject is not a good candidate for this particular study

Contacts and Locations

Locations

United States, California

University California San Diego

San Diego, California, United States, 92103

Naval Medical Center San Diego

San Diego, California, United States, 92134

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

University of California, San Diego

United States Department of Defense

United States Naval Medical Center, San Diego

The Cleveland Clinic

University of Texas MD Anderson

Walter Reed National Military Medical Center

Johns Hopkins University

Wake Forest Medical Center

Investigators

• Principal Investigator: Brian M Ilfeld, MD, MS; University California San Diego

More Information

• Responsible Party: Brian M. Ilfeld, MD, MS, Professor, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03461120 History of Changes
• Other Study ID Numbers: Phantom pain PREVENTION (DoD)
• First Posted: March 9, 2018
• Last Update Posted: April 26, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Phantom Limb; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Signs and Symptoms; Pain; Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents