Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04113954 |
| Other study ID # |
2019P002781 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
September 29, 2020 |
| Est. completion date |
April 6, 2021 |
Study information
| Verified date |
May 2021 |
| Source |
Brigham and Women's Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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. 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.
1. Hypothesis: There will be minimal or no change in pressure pain threshold and
tolerance and pain ratings with ACB alone
2. 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
2. Determine the concentration dependence of SNB-PF effect on pressure and ischemic pain by
comparing increasing doses of local anesthetic.
1. 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.
Description:
Please complete the survey (copy and paste into new link).
https://redcap.partners.org/redcap/surveys/?s=D4A4TN9TDL We will not contact you if the
survey is incomplete.
Please contact us via email (ykchen@partners.org) about this study with subject line
"Interested in participating in Compartment Syndrome Study"
Screening and Enrollment:
Healthy volunteers will be recruited, and all interested individuals will be invited to
contact study staff to hear more about the study requirements and undergo a brief phone
screen to determine eligibility. After their initial phone screen with study staff,
interested subjects meeting eligibility requirements will be provided with an electronic copy
of the consent form, perform a video consent, and schedule a study visit, to be conducted in
the Clinical Investigation Center at Brigham and Women's Hospital. A 5 hour, 1 office visit
is required.
All subjects will also undergo a survey-based COVID screen within 24 hours prior to the
study.
Study day:
Immediately upon arrival for their study appointment, the physician investigator will go
through the consent form in detail with each potential participant, and they will also be
given a chance to read it thoroughly and have questions answered. Special care will be taken
during the consent process to ensure subjects are fully competent and understand the nature
of the questionnaires and testing procedures, including a brief demonstration of the devices
and testing done. If agreeable to the study procedures after having questions answered,
participants will provide informed consent. Each participant will be assigned a random ID
number, and data will be collected, entered, and analyzed by ID number only. The subject's
status as a patient will be unaffected by his/her decision to participate. If subject decides
against participation at this point, they will be reimbursed for their time ($20).
Enrolled participants will complete basic deidentified demographic, clinical, psychosocial,
and pain questionnaires. Brief validated questionnaires will include the PROMIS anxiety,
depression, and sleep disturbance short forms, Pain Catastrophizing Scale (PCS), situational
pain catastrophizing scale (sPCS), Brief Symptom Index, Fibromyalgianess scale, Brief Pain
Inventory, Positive and Negative Affect Schedule, and pain coping strategies questionnaire.
After completing questionnaires, subjects will lie on a stretcher, with head of bed elevated
to 30-45 degree angle according to comfort, with legs and feet exposed for testing.
QST testing Pressure pain threshold: Pressure algometry is the most commonly used test for
static mechanical pressure sensation in the skin and in deep tissues. Pressure algometers
deliver a firm and quantifiable pressure through a flat base applied to the skin. The
electronic pressure algometer that we will use (Wagner Instruments) is a hand-held algometer
utilizing a pressure-sensitive strain gauge, covered by a 0.5 cm2 circular probe. The probe
is covered with a soft polypropylene disk, to avoid injury to the skin. The pressure applied
through the probe is transduced, amplified, and converted to electrical reading on a digital
display. The pressure will be slowly increased (1 lb/s) and the participant will be asked to
note when they first feel pain and when they want the pressure to stop , which will be
recorded as the pressure pain threshold and tolerance, respectively.120 This process will be
repeated on the trapezius and the forearm, alternating between sides of the body with 20
seconds between measurements.
Pin Prick: This tests the detection and intensity of sharp type pain. In addition, it is
often used as a modality to test temporal summation of pain with repeated stimuli. The
conductor of the test will touch the participant on the finger with weighted mechanical
probes in ascending order (64 mN, 128 mN, 256 mN, 512 mN), making sure to keep the probe
perpendicular to the skin, and allowing the full weight to be resting on this point (i.e. the
weight moves within the barrel), but without touching the barrel/cylinder itself to the skin.
The participant will be instructed to rate the pain (0-10) of each stimulation. The conductor
will make note of the lowest weight pin prick the participant indicated caused a 1-3 out of
10 pain. Then the conductor will perform the test of temporal summation to repeated punctate
stimuli, which is considered an index of central pain-faciliatory processes. The pin prick
weight that the participant noted was a 1-3 out of 10 pain is applied to the skin of the
dorsal fingers at a frequency of 1Hz. Ten stimuli are applied, and the patient will be asked
to rate the sensation of pain from the fifth, and tenth stimulus, as well as 15 seconds after
the end of the stimulus train (PAS). The wind-up phenomenon occurs with progressive increase
evoked pain with repeated stimulation and represents an index of central sensitization.
Testing order will be performed on each hand, bilaterally, and on each foot.
Pressure Pain Threshold Assessment:
Pressure pain will be assessed through response to cuff pressure algometry (CPA). Tonic,
deep-tissue, mechanical stimulation will be applied using a Hokanson rapid cuff inflator,
which allows specific calibrated pressures to by administered and held for defined time
periods. Using an adjustable cuff (similar to standard blood pressure cuff) wrapped around
the leg, centered around the largest diameter of the gastrocnemius muscle, pressure will be
increased by turning a manual dial at a rate of approximately 10-20 mmHg/second until the
subject first feels pressure, and thereafter at approximately 5-10 mmHg/s, at which time
subject will be asked to note when they first start feeling pain and then when they feel as
though the pain is a 4, 6, 8 and 10 out of 10 VAS score (0 = no pain, 10 = worst pain), after
which the cuff will be immediately deflated. Participants will be given a break. Cuff
pressure at each of these points will be recorded 3 times for each leg to determine baseline
pain thresholds.
Ischemic Pain Assessment:
The cuff will be re-inflated to the subject's average pressure previously determined to
produce 4 out of 10 pain for that leg, and held for 5 minutes. A pulse oximeter will be
placed on the big toe to monitor ischemia (pulse oximetry wave expected to disappear).
Subjects will be asked for pain score at rest every 30 seconds, and pain score on passive
stretch of gastrocnemius every 60 seconds. The participant will be reminded immediately
before cuff inflation that they may ask for the pressure cuff to be deflated at any time, in
which case this time will be recorded. Subjects will be asked to indicate the presence of
tingling (paresthesias), and will rate pain at rest 30 and 60 seconds following cuff
deflation (painful after sensations), as well as pain with passive stretch of gastrocnemius
at 60 seconds after cuff deflation.
There will be a 1 minute break, then the cuff pressure will be inflated to a pressure
corresponding to the next pain level as initially identified on the averaged baseline testing
(ex: if pressure 4/10 was 100 mmHg and 6/10 was 150 mmHg, cuff pressure will first be held at
100 mmHg and held for 5 minutes, followed by a 1 minute break, and then reinflated at 150
mmHg and held for 5 minutes, followed by 1 minutes break, etc.). The above procedure will be
repeated for cuff pressure at 6/10, 8/10, and 10/10. This will be done first on the "control
leg" and then on the "block leg" prior to the nerve block placement. Subjects will be
reminded that they may discontinue the cuff inflation at any point, and the time of cuff
inflation recorded.
IV placement:
A 20 g IV will be placed prior to the start of any nerve block procedure. Site of IV
placement will be cleaned with alcohol swab and initially anesthetized with 1% lidocaine
administered through a small needle to allow greater comfort with IV placement.
Nerve Blocks:
Saphenous Nerve Block (ACB):
Subjects will lie supine with block leg slightly abducted. Standard monitors will be applied
for vital monitoring (continuous pulse oximetry, EKG, blood pressure cuff every 5 minutes),
and this monitoring continued until 20 minutes after block completion. Using sterile
technique (cleaning of skin with chloroprep, sterile gloves, mask, sterile cap, sterile
needle, sterile ultrasound probe cover and sterile gel), an ultrasound-guided approach will
be used to identify the saphenous nerve and surrounding sonographic landmarks (sartorius
muscle, vastus medialis, femoral artery, femoral vein, and adductor magnus). With a small
needle, a small skin wheal of 1 cc of 1% lidocaine will be used to anesthetize the skin.
Afterwards a standard 21 g, 10 cm block needle will be inserted and directed under ultrasound
guidance to the saphenous nerve location. Aspiration on block syringe will be performed to
confirm that needle tip is not within a vascular structure to avoid intraarterial or venous
injection of local anesthetic. Incremental injection (5 cc at a time) of 1.5% mepivacaine
will follow, with a total of 10 cc (150 mg) deposited around the saphenous nerve.
Popliteal sciatic Nerve Block (SNB-PF): (for dual nerve block group only) Participant will
lie supine, with leg elevated to allow access to posterior leg for US scanning. Using sterile
technique, an ultrasound-guided approach will be used to identify the common peroneal nerve
and tibial nerve at the level of the popliteal fossa, and surrounding sonographic landmarks
(femur, popliteal artery, and popliteal vein). The common peroneal and tibial nerves will be
followed proximally by scanning proximally along the leg with the ultrasound until they form
a unitary nerve (sciatic). With a small needle, a small skin wheal of 1 cc of 1% lidocaine
will be used to anesthetize the skin of the lateral level at this level. Afterwards a
standard 21 g, 10 cm block needle will be inserted and directed under ultrasound guidance to
the sciatic nerve. Aspiration on block syringe will be performed to confirm that needle tip
is not within a vascular structure to avoid intraarterial or venous injection of local
anesthetic. Incremental injection (5 cc at a time) of 0.375% or 1.5% mepivacaine will follow,
with a total of 15 cc (56.25 mg or 225 mg) deposited around the sciatic nerve.
Expected timeline Pressure pain threshold assessment will take approximately 3 minutes and
Ischemic pain assessment approximately 30 minutes (5 minutes per inflation pressure with 1
minute for rest in between). Each assessment will be taken at baseline and 20 minutes after
nerve block completion to allow full effect. Ultrasound measures of compartment pressures
will be assessed before, during, and after pressure and ischemic pain assessment.
Resolution of Nerve block: Nerve blocks with mepivacaine are expected to be resolved within
4-6 hours, but monitoring will continue beyond this time as some normal variation in
resolution may occur between individuals. Subjects will only be given assistance with getting
off stretcher/chair if needed for 4 hours after nerve block placement. Strength testing of
target nerve groups in lower extremity will be confirmed before subject is allowed to walk
independently. Subjects gait and walking will be assessed and confirmed to be ambulating
safely before discharge.
