Clinical trial NCT01670825: Pulsed Radiofrequency vs. Steroid Injections for Occipital Neuralgia
Official title: Randomized, Double-blind, Comparative-effectiveness Study Comparing Corticosteroid Injections to Pulsed Radiofrequency for Occipital Neuralgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Occipital Neuralgia
Keywords: Occipital neuralgia
corticosteroid injection
pulsed radiofrequency
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: United States Naval Medical Center, San Diego
name: Landstuhl Regional Medical Center
name: Madigan Army Medical Center
name: United States Naval Medical Center, Portsmouth
First posted: 2012-08-22
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to determine whether pulsed radiofrequency or steroids are better for occipital neuralgia. Seventy-six patients with ON or migraine with tenderness over the occipital nerve who respond to occipital nerve blocks (hereafter included under the broad category "ON") will be randomized in a 1:1 ratio to receive either corticosteroid and local anesthetic injections (n=38) or local anesthetic and PRF of the occipital nerve(s) (n=38) for occipital neuralgia. Both patients and the treating \& evaluating physicians will be blinded. The first follow-up visit will be at 6 weeks. Patients who obtain significant pain relief will remain in the study. Those patients who fail to obtain any benefit will exit the study and be allowed to crossover to the other treatments or receive alternative care. The second follow-up will be at 3 months and the final follow-up will be at 6-months post-procedure.

Detailed description: Up to 76 patients referred to one of the participating pain clinic with occipital neuralgia, or migraines with occipital nerve tenderness (dual diagnoses) will be randomized in a 1:1 ratio by a computer generated randomization table to receive one of two treatments. Treatments will be randomized at each institution. Within each group, those patients with plain occipital neuralgia, and those with occipital neuralgia with migraines, will be sub-randomized in the same 1:1 ratio. Diagnosis of ON will be made by low-volume (\< 3 mL bupivacaine per nerve). Our criterion for a positive response will be \> 50% pain relief lasting at least 3 hours. Those individuals who have symptoms in the distribution of both the greater and lesser occipital nerves will receive treatment of both nerves. The greater occipital nerve is more frequently affected than the lesser nerve.

Half (n=38) of the patients will be allocated to receive local anesthetic \& corticosteroid injections at each nerve (group I), with an equal number allocated to receive local anesthetic \& PRF at each (group II). In those patients who request sedation, an intravenous will be inserted and light sedation administered with low doses of midazolam and fentanyl, in accordance with our standard clinic practice. Treatment in all patients will be accomplished using 20-gauge radiofrequency needles with 10 mm active tips. Prior to treating, electrical stimulation will be performed to ensure ample proximity to the targeted nerve(s), with our target threshold being concordant stimulation at \< 0.3 volts at each site.

Once proper needle position is ensured, those in group I will receive an injection at each nerve containing 30 mg of depomethylprednisolone mixed with 2 mL of a 50:50 mixture of 2% lidocaine and 0.5% bupivacaine (2.75 mL). Anywhere between 1 and 4 nerves can be injected, with 4 nerves being targeted if a patient had bilateral lesser and greater occipital nerve involvement. This will be followed by 3 cycles of sham PRF at 120 s per cycle, with slight (approximately 30o electrode adjustments between cycles. For sham PRF, no electrical field or heat is generated (i.e. the machine is not set to any radiofrequency cycle after stimulation), but the cycle times (120 s per cycle) are adhered to (i.e. we will wait a total of 6", 2" per cycle). Those patients in group II will receive injections at each nerve containing 2.75 mL of a solution with 2 mL of 50:50 2% lidocaine and 0.5% bupivacaine + 0.75 mL saline (2.75 mL), followed by 3 cycles of PRF using the following standard settings: voltage output 40-60 V; 2 Hz frequency; 20 ms pulses in a 1-second cycle, 120 second duration per cycle; impedance range between 150 and 400 Ohms; and 42o C plateau temperature.

No patient will be prescribed additional medications or therapy between their procedure and first follow-up. However, they will be allowed to remain on their current, stable analgesic regimen. Rescue medications will consist of tramadol 50 mg 1 to 2 tablets every 6 hours PRN (up to 8/d) and/or acetaminophen or a non-steroidal anti-inflammatory drug such as ibuprofen, diclofenac or ketorolac on an "as needed" basis.

Follow-ups will be performed by a physician blinded to treatment allocation. A preliminary follow-up will be performed at weeks. The first full follow-up visit will be scheduled 6-weeks from the start of treatment. A positive outcome will be defined as a \> 50% decrease in headache coupled with a positive satisfaction rating (\> 3 on a 0-5 scale). Subjects who obtain a positive outcome at their initial 6-week follow-up visit will remain in the study and return for their 3-month follow-up visit. Those with a negative outcome will exit the study "per protocol" to receive standard care. Subjects who obtain a positive outcome at 1-month but experience a recurrence before their 3-month follow-up visit will also exit the study per protocol, with their final outcome measures recorded before they receive standard care. Those who obtain a positive outcome at 3-months will remain in the study for their final 6-month follow-up, while those who obtain a negative outcome will exit the study. Unblinding for both patients and the treating physician will be after the patient exits the study or after their final follow-up visit for those with continued benefit.

Eligibility criteria: Inclusion Criteria:

1. Age greater or equal to 18 years
2. Occipital neuralgia diagnosed based on history \& physical exam and diagnostic local anesthetic blocks, or migraine with occipital nerve(s) tenderness that responds to diagnostic blocks.

   a. Greater or equal to 50% relief based on diagnostic local anesthetic block of the greater and/ or lesser occipital nerves that lasts for at least 90 minutes with lidocaine or 3 hours with bupivacaine or ropivacaine 20
3. Baseline Numerical Rating Scale average pain score \> 4/10
4. Frequency of greater or equal to 4/10 pain for at least 10 days per month

Exclusion Criteria:

1. Untreated coagulopathy
2. Automatic implantable cardiac defibrillator or pacemaker that cannot be temporarily disabled for medical reasons
3. Previous pulsed radiofrequency
4. Other sources of headache, such as tension-type headache, cervicogenic headache, migraine headache without occipital neuralgia, and other causes (e.g. tumors, congenital abnormalities etc.). Those that can be confused with ON must be excluded based on history and exam (e.g. cervicogenic headaches), symptoms (tension-type headache), response to blocks (all of the above); and lab work (temporal arteritis, which would be confirmed by biopsy after an elevated erythrocyte sedimentation rate).
5. Serious medical or uncontrolled or severe psychiatric -

Primary outcomes:
measure: Change in Average Occipital Pain 6 Weeks After the Start of Treatment
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in Worst Occipital Pain 6 Weeks After the Start of Treatment
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in Average Occipital Pain 6 Months After the Start of Treatment
timeFrame: From baseline to 6 months after the start of treatment
measure: Change in Worst Occipital Pain 6 Months After the Start of Treatment
timeFrame: From baseline to 6 months after the start of treatment
measure: Change in Average Occipital Pain 3 Months After the Start of Treatment
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in Worst Occipital Pain 3 Months After the Start of Treatment
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in Average Occipital Pain 2 Weeks After the Start of Treatment
timeFrame: From baseline to 2 weeks after the start of treatment
measure: Change in Worst Occipital Pain 2 Weeks After the Start of Treatment
timeFrame: From baseline to 2 weeks after the start of treatment
measure: Change in Overall Average Headache Pain 2 Weeks After the Start of Treatment
timeFrame: From baseline to 2 weeks after the start of treatment
measure: Change in Overall Worst Headache Pain 2 Weeks After the Start of Treatment
timeFrame: From baseline to 2 weeks after the start of treatment
measure: Change in Overall Average Headache Pain 6 Weeks After the Start of Treatment
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in Overall Worst Overall Headache Pain 6 Weeks After the Start of Treatment
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in Overall Average Headache Pain 3 Months After the Start of Treatment
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in Overall Worst Headache Pain 3 Months After the Start of Treatment
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in Overall Average Headache Pain 6 Months After the Start of Treatment
timeFrame: From baseline to 6 months after the start of treatment
measure: Change in Overall Worst Headache Pain 6 Months After the Start of Treatment
timeFrame: From baseline to 6 months after the start of treatment
Secondary outcomes:
measure: Change in the Presence of Insomnia 6 Weeks After the Start of Treatment Measured Using the Athens Insomnia Scale.
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in the Presence of Insomnia 3 Months After the Start of Treatment Measured Using the Athens Insomnia Scale.
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in the Presence of Insomnia 6 Months After the Start of Treatment Measured Using the Athens Insomnia Scale.
timeFrame: From baseline to 6 months after the start of treatment
measure: Change in the Severity of Depression 6 Weeks After the Start of Treatment Measured Using the Beck's Depression Inventory
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Change in the Severity of Depression 3 Months After the Start of Treatment Measured Using the Beck's Depression Inventory
timeFrame: From baseline to 3 months after the start of treatment
measure: Change in the Severity of Depression 6 Months After the Start of Treatment Measured Using the Beck's Depression Inventory
timeFrame: From baseline to 6 months after the start of treatment
measure: Severe Headache Frequency for Migraine Headaches 6 Weeks After the Start of Treatment Measured Asking the Number of Severe Headaches in the Past Week.
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Severe Headache Frequency for Occipital Neuralgia Headaches 6 Weeks After the Start of Treatment Measured Asking the Number of Severe Headache Days 1 Week Prior to Study Visit
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Severe Headache Frequency for Migraine Headaches 3 Months After the Start of Treatment Measured Asking the Number of Severe Headache Days 1 Week Prior to Study Visit
timeFrame: From baseline to 3 months after the start of treatment
measure: Severe Headache Frequency for Occipital Neuralgia Headaches 3 Months After the Start of Treatment Measured Asking the Number of Severe Headache Days 1 Week Prior to Study Visit
timeFrame: 3 months
measure: Severe Headache Frequency for Migraine Headaches 6 Months After the Start of Treatment Measured Asking the Number of Severe Headache Days 1 Week Prior to Study Visit
timeFrame: From baseline to 6 months after the start of treatment
measure: Severe Headache Frequency for Occipital Neuralgia Headaches 6 Months After the Start of Treatment Measured Asking the Number of Severe Headache Days 1 Week Prior to Study Visit
timeFrame: From baseline to 6 months after the start of treatment
measure: Disability Due to Headaches 6 Weeks After the Start of Treatment Measured Using the Headache Impact Scale
timeFrame: From baseline to 6 weeks after the start of treatment
measure: Disability Due to Headaches 3 Months After the Start of Treatment Measured Using the Headache Impact Scale
timeFrame: From baseline to 3 months after the start of treatment
measure: Disability Due to Headaches 6 Months After the Start of Treatment Measured Using the Headache Impact Scale
timeFrame: From baseline to 6 months after the start of treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
Study officials:
References:
citation: Huang JH, Galvagno SM Jr, Hameed M, Wilkinson I, Erdek MA, Patel A, Buckenmaier C 3rd, Rosenberg J, Cohen SP. Occipital nerve pulsed radiofrequency treatment: a multi-center study evaluating predictors of outcome. Pain Med. 2012 Apr;13(4):489-97. doi: 10.1111/j.1526-4637.2012.01348.x. Epub 2012 Mar 5.
citation: Vanelderen P, Rouwette T, De Vooght P, Puylaert M, Heylen R, Vissers K, Van Zundert J. Pulsed radiofrequency for the treatment of occipital neuralgia: a prospective study with 6 months of follow-up. Reg Anesth Pain Med. 2010 Mar-Apr;35(2):148-51. doi: 10.1097/aap.0b013e3181d24713.
citation: Choi HJ, Oh IH, Choi SK, Lim YJ. Clinical outcomes of pulsed radiofrequency neuromodulation for the treatment of occipital neuralgia. J Korean Neurosurg Soc. 2012 May;51(5):281-5. doi: 10.3340/jkns.2012.51.5.281. Epub 2012 May 31.
citation: Cohen SP, Peterlin BL, Fulton L, Neely ET, Kurihara C, Gupta A, Mali J, Fu DC, Jacobs MB, Plunkett AR, Verdun AJ, Stojanovic MP, Hanling S, Constantinescu O, White RL, McLean BC, Pasquina PF, Zhao Z. Randomized, double-blind, comparative-effectiveness study comparing pulsed radiofrequency to steroid injections for occipital neuralgia or migraine with occipital nerve tenderness. Pain. 2015 Dec;156(12):2585-2594. doi: 10.1097/j.pain.0000000000000373.