Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05734625 |
| Other study ID # |
22-007151 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
July 10, 2023 |
| Est. completion date |
July 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Mayo Clinic |
| Contact |
Family Medicine Research Study Coordinators |
| Phone |
507-422-6823 |
| Email |
RSTFMSC[@]mayo.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to see how well blocking two to ten of the scalp nerves (that
give feeling to the scalp and are painful during migraine headaches) with bupivacaine
anesthetic (numbing medication) and low dose methylprednisolone (cortisone-like medicine or
steroid) work for treating and preventing migraines. Our hypothesis is that the pain of most
episodic migraine headaches can be eliminated and prevented for months by blocking the nerves
that give pain sensation during a migraine.
Description:
Hypothesis: Multiple peripheral nerve blocks provide more complete acute headache relief and
better headache prophylaxis in episodic migraine than greater occipital nerve blocks alone.
Aims, purpose, or objectives:
Compare whether anesthetizing multiple peripheral nerves of the scalp (also known as multiple
peripheral nerve block (MPNB)) provides more acute headache pain relief than greater
occipital nerve block (GONB) alone.
Compare whether MPNB provides better headache prophylaxis than GONB alone measured monthly
for three months.
Determine whether there are fewer missed work/school/life activity days measured monthly for
three months following nerve block for patients who receive MPNB compared to patients who
receive GONB.
Compare whether there are fewer Emergency Room/Clinic visits for headache measured monthly
for three months follow up for patients who receive MPNB compared to patients who receive
GONB.
Background
Peripheral nerve blocks (PNBs) have been studied in randomized trials and have proven
beneficial and safe to varying degrees in the treatment of episodic migraine. Most of these
studies have evaluated GONBs; two have looked at the combination of GONB and supraorbital
nerve block (SONB). No study to date measuring pain relief in acute migraine and prophylaxis
reported scalp anesthesia thus making conclusions about effect size of an actual nerve block
on acute headache and prophylaxis or conclusions about optimal method, medication dosages and
frequency of block(s) difficult.
The PI has observed in his experience over 17 years administering many thousands of
peripheral nerve blocks at MCR that essentially all patients get complete acute headache
relief and most get durable prophylaxis for months if nerve blocks are administered in the
distribution of a patient's presenting headache and anesthesia is confirmed and documented in
all nerves in the scalp distribution of the headache (as many as 12 PNBs per patient to
include bilateral greater occipital, lesser occipital, auriculotemporal, supraorbital,
supratrochlear nerves, and infraorbital nerves).
In this study we will be randomizing patients to receive either GONBs alone or MPNBs to
include all 10 scalp nerves and excluding patients with facial pain in the infraorbital nerve
distribution during migraines.
Study Design and Methods
Methods:
Subjects with EMR documented episodic migraine headaches (defined as 14 or less headache days
per month, frequency of which can be assessed at the time of initial discussion with the
study coordinator) will be recruited from our local patient population. Study coordinators
will then schedule a screening phone visit to explain the study and validate
inclusion/exclusion criteria and obtain written consent either digitally, in person or
eConsent and enroll the subject in the study.
The research coordinator will then provide each subject with an initial questionnaire to
obtain baseline data including episodic migraine headache diagnosis, history of secondary
headache causes, location of their usual headache, where in the head it starts and the
progression, frequency, severity on 10 point VAS, duration, associated symptoms including
aura, characteristics, associated disability with MIDAS score, current medications for acute
treatment and prophylaxis and their effectiveness.
Consented subjects will receive weekly for one month an electronic headache diary to report
headache days of that prior week by day and date, functional rating scale, pain intensity,
associated symptoms, location of headache, any missed work/school/life activity days, acute
medications used and clinic or transfusion center or emergency room visits for headache.
After the one-month run-in, the research coordinators will contact the subjects to affirm
that they are now ready for an injection when they get their next acute migraine that is at
least 5/10 severity on a Monday through Friday and ask them not to take their usual acute
migraine rescue treatment unless that usually only blunts the pain to no less than 5/10.
The subject will then call to be scheduled in our Procedure Clinic on a Monday through Friday
when they have a typical acute migraine. Their appointment will be scheduled on that same
half-day with one of the Co-I's or PI and the appointment reason noted as acute migraine for
nerve blocks. If no slot is available within 24 hours, they will encourage the subject to
care for their migraine in their usual way and to call again with the next headache later
that month.
A brief interval history will be obtained by the investigator at the time of the appointment
to confirm the details on an interval history questionnaire filled out by the patient earlier
that day. Randomization codes generated by the statistician and kept in sealed opaque
envelopes in the Procedure Clinic in a sequential order numbered #1 - #60 will be opened by
the physician investigator performing the injection at the time of the visit. Block
randomization will be utilized with random block sizes to provide balanced numbers in each
group. Subjects in the GONBs group will then receive bilateral GONBs for a total of 2 blocks.
Subjects in the MPNBs group will receive 10 nerve blocks to include greater occipital, lesser
occipital, auriculotemporal, supraorbital and supratrochlear nerves. Investigators performing
the blocks will only use neutral language to ensure that no bias is created by implying the
subjects are "only getting the GONBs" or "are getting all of the blocks not just a couple."
Headache pain scores will be obtained from each subject at baseline, and every 5 minutes
after completing the first injection. until 5 minutes after anesthesia is verified in all
intended to be blocked nerve distributions. Any residual headache pain present 10 minutes
after injections are completed will be identified and recorded by scalp location (central
back of head, lateral back of head, temples, forehead, central forehead above the nose) and
sidedness (left or right or both) and anesthesia in those nerve distributions assessed. If
there is pain and lack of anesthesia in the dermatomal distributions of nerves not intended
to be blocked the investigator will affirm the findings as "ok, good." Any residual sensation
to pain on pinprick in a nerve distribution intended for block will be re-blocked. Any
repeated blocks will be recorded in the procedure note. Only anesthetic will be used for
repeat blocks. Nerve blocks will be reperformed in the sequence listed below until all
intended nerve blocks are verified. VAS pain scores will be recorded until 20 minutes after
the last nerve intended for block is proven anesthetic.
A questionnaire will be sent to each subject one day after their nerve block to ask them if
they had complete headache relief, whether the headache came back later when the anesthesia
wore off, their headache pain score that day (day after the nerve blocks), and to assess side
effects of the PNBs to include pain, bruising, transient visual or facial motor changes.
Subjects will be sent an electronic headache seven-day diary weekly for 3 months beginning 1
week after their nerve blocks to report the days of that prior week they had a headache,
acute medications used if any, a functional rating scale, maximal pain intensity each day,
headache associated symptoms, any missed work/school/life activity days, and any clinic or
transfusion center or emergency room visits for headache.
The primary outcome variable will be complete regression of headache pain on the day of PNBs
as defined by VAS. This will be assessed both by pain score and scalp location (central back
of head, lateral back of head, temples, forehead, central forehead above the nose) and
sidedness (left or right or both). Neck pain as commonly seen in migraine and other headache
disorders will not be counted as headache pain. Secondary outcome variables will be degree of
prophylaxis of future headaches in terms of reduction in severity and frequency from
historical severity and frequency of the subject's headaches and reduction in lost days of
work/school/life events vs. lost days of work/school/life events during the month
pre-injection and clinic/emergency room/transfusion clinic visits for headache vs. those in
the one month prior to PNBs.
Blinding
This will be a pragmatic randomized comparison trial. GONBs and MPNBs will act as the
treatment arms. Research subjects will be informed that they are in a trial of nerve blocks
in treatment and prevention of migraine headache and may receive up to 10 nerve blocks. The
language of consenting will seek to minimize bias by seeking to avoid suggesting that more
blocks are better than less as follows: "There are small and large nerves all over the front,
back and sides of your head that can contribute to a migraine headache. In this study,
subjects will get nerve blocks in various combinations of one or two or up to 10 nerves at a
time. The nerves blocked may or may not respond to the location of your pain."
Intervention
Subjects will be randomized to receive either GONBs or MPNBs in the following methods:
Greater occipital nerve (GON) blocks will be performed with head of patient prone on the
table footrest with each block containing a mixture of 1.25 ml bupivacaine 0.5% and 20 mg
methylprednisolone (for GONB only or 10 mg for MPNB so then getting 40 mg total in both
groups) administered by a 3 ml syringe with a ¾" 30g needle. The block(s) will be performed
in the following sequence until GON nerve distribution anesthesia is obtained: 2 cm inferior
and 2 cm lateral to the inion (or lacking an occipital protuberance, a central point of their
occiput that is 3 cm from the midline nuchal edge will be assigned as inion hereafter called
"inion")), or failing to achieve anesthesia an anesthetic only injection at 22% of the
distance from the inion to the mid-inferior mastoid (as per Loukas et al, 2006), or failing
to achieve nerve block at the second location after 10 minutes, an anesthetic only injection
at 3 cm inferior and 1 cm lateral to the inion.
Lesser occipital nerve (LON) blocks will be performed with the head of patient prone on the
table footrest with each block w/ 1.25 ml bupivacaine 0.5% and 10 mg methylprednisolone
administered by a 3 ml syringe and a ¾" 30g needle in the following sequence until LON nerve
distribution anesthesia is obtained: 30% of the distance from mid-inferior mastoid to inion
determined location and location confirmed to be over cranium, and failing to achieve
anesthesia an anesthetic only injection into the sulcus just posterior to the mastoid and
failing to achieve anesthesia with the first two locations after 10 minutes, an anesthetic
only injection at a location just 3-4 mm medial to the first 2 will be chosen that is over
cranium.
Auriculotemporal nerve (ATN) blocks will be performed with patient supine with each block
containing 1 ml of bupivacaine 0.5% without steroid administered by a 3 ml syringe and a 30g
¾" needle until ATN nerve distribution anesthesia is obtained. Location of the first block
attempt will be in the superior edge of the tragus fold formed by forward displacement of the
tragus (just superior to the ATN neuroforamen at the superior posterior fossa of the
maxilla's TMJ and 3-4 mm posterior to the temporal artery). Location of the second block
attempt if not anesthetic after 10 minutes will be 2-3 mm anterior of the anterior superior
edge of the helix at a depth of ½ cm.
Supraorbital nerve (SON) blocks will be performed with patient supine with each block
containing 1 ml of bupivacaine 0.5% without steroid administered by a 3 ml syringe and a 30g
¾" needle until SON nerve distribution anesthesia is obtained. Any injected site will be held
firmly afterwards for at least 2 minutes and longer if bleeding persists. Location of the
first block attempt will be 0.25 cm above the supraorbital rim along a vertical line drawn
through the medial iris of a forward gazing eye, marked with ear speculum tip, prepped with
chlorhexidine-alcohol, and injected tightly against the cranium (so as to in part provide
subgaleal infusion to get the deep branch of the SON that may be subgaleal) 0.5 ml just 0.25
cm superior to the supraorbital rim at the marked location and then another 0.5 ml injected
just inferior to the supraorbital rim after walking the needle tip along the same vertical
line off the edge of the supraorbital ridge (injected perpendicular through eyebrow displaced
inferiorly with finger under rim firmly to prevent upper lid edema from the injection or a
scar in the skin, only the eyebrow) at an additional depth of 2 mm below the rim, immediately
withdrawn and firm pressure applied to both sites with flexed tip digit for 2 minutes to
prevent ecchymosis from the supraorbital artery with additional pressure applied as needed if
still bleeding. Location of the second block attempt if not anesthetic after 10 minutes will
be just medial or lateral to the first depending on which branch is not successfully blocked
by the first attempt.
Supratrochlear nerve (STN) blocks will be performed with patient supine with each block
containing 0.5 ml of bupivacaine 0.5% without steroid administered by a 3 ml syringe and 30g
¾" needle and repeated as needed. The site will be held firmly afterwards for at least 2
minutes and longer if bleeding persists. Only one location is needed for this block since it
essentially never misses and the STN neuroforamen at a location ½ of the distance from the
SON to the inner canthus of the eye is easily palpable in everyone.
Time to complete the GONBs or MPNBs will be recorded along with any need for repeat
injection(s) specifying where they were repeated in the procedure note. Headache VAS pain
score will be obtained at 5, 10, 15, 20 and in 5-minute intervals thereafter until all
intended nerves are blocked as verified by pin-prick anesthesia.
Human Subject Protection
Informed consent will be obtained from all subjects by research study coordinators. This
study with PNBs poses moderate risk of transient pain, bleeding, and bruising, low risks of
infection, allergic reaction, scarring, hypo or hyperpigmentation, dizziness or
light-headedness or even fainting, low risk of dermal atrophy (skin dimpling) or focal hair
loss of a few mm around the occipital nerve block sites from the steroid, rare cases of
transient (6-8 hour) facial nerve palsy if auriculotemporal block is placed too far inferior
and anterior to the location intended and a risk of inefficacy meaning the nerve blocks don't
help the headache pain. Other risks mentioned in the literature are specific to errors in
judgment and care (e.gs. a case of coma resulted from doing a GON block on a patient who had
had a craniotomy and so the injectate traveled intracerebral). Total steroid dose will be 40
mg for the GONB arm and 40 mg for the MPNB arm, doses commonly well-tolerated for a variety
of depo-steroid uses.
Since both GONBs and MPNBs are presently standard of care for different consultants in
different departments at our institution, safety monitoring will be through assessment of
post-injection anesthesia and compliance with injection and anesthesia assessment technique
and assuring repeat injection to the point of anesthesia to ensure both safety and data
validity.
Conduct of the Study
The study will run until all subjects in each arm have received their nerve blocks and
completed the 12-week post-injection follow up.
