Detecting Compartment Syndrome Pain in the Presence of Regional Anesthesia in Healthy Volunteers

NCT04113954 | Completed Phase 1 FDA Drug

• 1 other identifier: 2019P002781
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to determine how different types of Regional Anesthesia (nerve blocks) can be helpful to patients with lower extremity trauma who develop compartment syndrome (an increased pressure in the fascial compartments) which can occur after injury to the leg. This is a prospective, randomized study in healthy volunteers, who will undergo testing of the leg using a cuff inflation system, involving quantitative sensory testing (QST), questionnaire completion, with ultrasound scanning and nerve blocks in a supervised, monitored setting (BWH Clinical Investigation Center). Specific Aims

1. 1.Determine the effect of adductor canal-saphenous nerve block (ACB) and popliteal-fossa nerve block (SNB-PF) vs no block on pressure and ischemic pain in a model of compartment syndrome.
2. 2.Hypothesis: There will be minimal or no change in pressure pain threshold and tolerance and pain ratings with ACB alone
3. 3.Hypothesis: There will be an increase in pressure pain threshold and tolerance and decrease in pain ratings with ACB plus popliteal-fossa nerve block (SNB-PF), compared to no block
4. 4.Determine the concentration dependence of SNB-PF effect on pressure and ischemic pain by comparing increasing doses of local anesthetic.
5. 5.Hypothesis: There will be a greater increase in pressure pain threshold and tolerance and great decrease in pain ratings with 1.5% mepivacaine than with 0.375% mepivacaine.

Conditions

Compartment Syndrome of Leg; Healthy

Keywords

Healthy volunteer; Regional anesthesia; Compartment Syndrome

Outcome Measures

Primary Outcomes (3)

• Pressure-pain threshold and tolerance

  Pressure (mmHg) in cuff corresponding to pain score 4, 6, 8, and 10 out of 10 based on visual analog scale (VAS)

  2 hours

• Ischemic pain threshold and tolerance

  Cuff inflation to predetermined pressure (mmHg) corresponding to pain score of 4, 6, 8, and 10 out of 10 based on pressure-pain threshold, and held for up to 5 minutes. Pain scores recorded every 30 seconds, pain scores every 1minute with passive stretch of the gastrocnemius.

  2 hours

• Ultrasound measurement of pressure in compartment in leg

  Measurement of ultrasonographic qualities of compartments in the leg using both standard imaging as well shear wave elastography in response to varying external pressure of probe (0-22mmHg) using an external load sensor attached to the probe handle during pressure testing and block recovery, in the absence and presence of a thigh cuff set to 70 mmHg (non-painful pressure).

  1 hour

Study Arms (6)

Leg 1 ACB + low dose SNB-PF

EXPERIMENTAL

Right leg and 0.375% mepivacaine popliteal fossa-sciatic

Drug: Mepivacaine Injection

Leg 1 ACB + high dose SNB-PF

EXPERIMENTAL

Right leg and 1.5% mepivacaine popliteal fossa-sciatic

Drug: Mepivacaine Injection

Leg 2 ACB + low dose SNB-PF

EXPERIMENTAL

Left leg and 0.375% mepivacaine popliteal fossa-sciatic

Drug: Mepivacaine Injection

Leg 2 ACB + high dose SNB-PF

EXPERIMENTAL

Left leg and 1.5% mepivacaine popliteal fossa-sciatic

Drug: Mepivacaine Injection

Leg 1 ACB only

EXPERIMENTAL

Right leg and 1.5% mepivacaine ACB

Drug: Mepivacaine Injection

Leg 2 ACB only

EXPERIMENTAL

Left leg and 1.5% mepivacaine ACB

Drug: Mepivacaine Injection

Interventions

Mepivacaine Injection DRUG

Injection of 0.375% mepivacaine in nerve block

Also known as: Prilocaine

Leg 1 ACB + high dose SNB-PF; Leg 1 ACB + low dose SNB-PF; Leg 2 ACB + high dose SNB-PF; Leg 2 ACB + low dose SNB-PF

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old, ≤ 65 years old
• BMI \< 35
• Able to speak and understand English
• Willingness to undergo psychophysical testing
• Willingness to have nerve block performed

You may not qualify if:

• Ongoing acute or chronic pain in lower extremities
• Diagnosis of neuropathy
• Diagnosis of diabetes
• History of chronic opioid use (having an opioid prescription \> 30 days)
• Loss of any limb
• Currently pregnant
• Any skin conditions or breakdown of skin affecting lower extremities
• Current history of peripheral arterial disease
• History of blood clot in any lower extremity
• Current smoking/vaping of nicotine or illicit substances including marijuana

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Massachusetts Institute of Technology: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Chen YK, Lirk P, Flowers KM, Colebaugh CA, Wilson JM, Zeballos J, Von Keudell A, Barrett KE, Vlassakov K, Schreiber KL. Impact of varying degrees of peripheral nerve blockade on experimental pressure and ischemic pain: adductor canal and sciatic nerve blocks in a human model of compartment syndrome pain. Reg Anesth Pain Med. 2022 Jul 20:rapm-2022-103671. doi: 10.1136/rapm-2022-103671. Online ahead of print.

  PMID: 35858717 DERIVED

MeSH Terms

Conditions

Compartment Syndromes

Interventions

Mepivacaine; Prilocaine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Kristin Schreiber, MD/PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participant will be masked to the drug being provided in the nerve blocks (0.375% mepivacaine or 1.5% mepivacaine)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Our patients will be randomized to one of six arms.

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 3, 2019
• Study Start: September 29, 2020
• Primary Completion: April 6, 2021
• Study Completion: April 6, 2021
• Last Updated: May 14, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)