Clinical trial NCT05382832: Botox Vs Spinal Cord Stimulation in the Treatment of Refractory Migraine Clinical Trial
Official title: Botox Vs Spinal Cord Stimulation in the Treatment of Refractory Migraine
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Migraine
Lead sponsor: Europainclinics z.ú.
Sponsor class: OTHER
Collaborators: name: National Hospital for Neurology and Neurosurgery, London
First posted: 2022-05-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-Blinded, Randomized, Controlled Trial
Primary purpose: TREATMENT

Brief summary: The clinical trial is focused on the treatment of selected patients with a migraine after implantation of spinal cord stimulator (SCS) based on previous neurological examination. Patients will be randomized and divided into two groups. According to randomization patients will receive saline or botox into the epidural space. The efficacy of treatment will be compared and estimated in both groups during different SCS settings. Data will be collected in pre-set time frames.

Detailed description: This study consists of a double-blind randomized cross-over controlled trial (RCT). Enrolled centers are National Hospital For Neurology and Neurosurgery in London in the United Kingdom, EuroPainClinics® with centers in Bratislava, Košice, and Bardejov in the Slovac republic and also EuroPainClinics® with centers Praha, Brno, Ostrava, and Hradec Kralove in the Czech republic.

Patients with diagnosing migraine (examined previously by neurologist) suitable for participating in the clinical trial, without any previous Botulinum Toxin treatment or Spinal Cord Stimulation therapy, (after exact consultation by neuromodulation team) will be offered to enroll in the BoStiM trial.

Enrolled patients will have a full implant of Nevro Senza SCS system. The intervention will be performed at the National Hospital for Neurology and Neurosurgery in London in the United Kingdom, and also in st. Michal Hospital in Bratislava in the Slovak Republic and General University Hospital in Prague in the Czech Republic. The procedure will be performed by the Neuromodulation Team. The implanted SCS will be turned off at this stage and will stay off for 2 weeks' time to let the wounds heal properly and not interfere with headache measurements. Once enrolled in the study, the patients will be randomized into one of the two groups of study. Groups will consist in either first SCS treatment, then washout period, then Botox treatment or SCS, then washout, then Botox. All patients will therefore be their own controls, and all of them will receive both treatments. After randomization, patients will be added to the SCS pathway. During the period between enrolment and SCS implant, patients will have the opportunity to meet the psychology team at the Pain Management Centre (PMC) and will undergo teaching sessions to learn the basic SCS practical aspects.

Blinding technique:

In order to have a double-blinded RCT, the investigators will not be aware of the trial branch of the participants.

Injections will be performed either with Botulinum Toxin or with Normal Saline and Spinal Cord Stimulators will be configured in order to use high-frequency stimulation or a sham treatment. All Internal Pulse Generators (IPG) will be turned on throughout the trial so as to avoid the participants being able to know the treatment they're really receiving at that time. Participants receiving Botox injections will have their IPG running with a sham configuration. They will not be receiving any electric stimulation over the leads, but the battery will be programmed to have a current leakage and will need to be recharged so as if the IPG was properly working. This again is to avoid them knowing which treatment they're receiving at any time being. The Clinical Specialist Nurses (CNS) of our PMC will be in charge of labeling the Botox/Placebo vials, which will be anonymized, and they will also be in charge of setting up the SCS (sham or treatment).

Data collection:

The enrolled patients will be provided a Smartphone to assess the migraine episodes. Each Smartphone will have an in-built app that the patients will use daily, and that will send the results to the research team. Those patients preferring to use their own smartphone will need to download the app to their smartphone. The app will include a visual numeric scale (VNS) that the participants will need to fulfill daily, as well as qualitative questions including the type of migraine, the onset, presence or absence of aura, duration of the episode, and possible medication intake.

The first period of trial:

The proper trial period will start two weeks after the implant (week 1). On this day, patients will be invited to come to the PMC. Depending on the randomization group, patients will have either a Botox Injection and the SCS Internal Pulse Generator turned on in sham-mode or a placebo injection and the IPG turned on in proper working mode. Patients will be given a controller for the IPG so that they may be able to turn it off in case of an emergency. They will nonetheless not be able to change the program. None of the investigators will be aware of the group. At week 12, participants will have a new injection of either Botox or Placebo and will be reviewed by the CNS and Nevro team to assess any problems. At that time, they will also be asked to complete through the Smartphone app the Quality of Life (QoL) questionnaires and will be asked to guess their branch. Washout period: At week 24, all participants will undergo a washout period of 1 month. They will be invited to come to the PMC and IPG (both sham and treatment) will be turned off. They will also be asked to fill the QoL questionnaires.

Second Period of Trial:

At week 28, participants will be invited to come to the PMC and they will start the second part of the trial, being assigned to the other branch. All IPG's will be turned on, those previously being actively treating will be turned to the sham mode and the opposite will be done with previously sham mode ones. Patients previously receiving placebo injections will receive a Botox injection on that day, and those previously receiving Botox injections will receive a placebo one. Quality of life questionnaires will be filled. At week 40, participants will undergo the 4th and last series of injections (Botox or placebo) and will have an assessment with CNS and Nevro team, and will be asked to fill in the usual questionnaires.

End of trial:

The trial will end at week 52 when patients will be asked to fill in the usual questionnaires. At that moment, they will be communicated to which branch they had been assigned.

Patients will then decide whether they want to keep the SCS system or prefer it removed.

Eligibility criteria: Inclusion Criteria:

* migraine presence

Exclusion Criteria:

* disagreement with participation in the study

Primary outcomes:
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 14 days after the SCS implant
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 91 days after the SCS implant
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 175 days after the SCS implant
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 196 days after the SCS implant
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 280 days after the SCS implant
measure: Health Questionnaire (EQ-5D-5L)
timeFrame: 364 dayss after the SCS implant
Secondary outcomes:
measure: Visual numeric scale
timeFrame: daily up to 10 days
measure: Type of migraine
timeFrame: up to 1 week
measure: Aura presence
timeFrame: up to 1 week
measure: Duration of the migraine episode
timeFrame: up to 1 week
Other outcomes:
Locations:
Study officials:
affiliation: EuroPainClincs
name: Róbert Rapcan, MD, PhD, MBA, FIPP
role: STUDY_CHAIR
affiliation: EuroPainClincs
name: Ladislav Kočan, MD, PhD
role: STUDY_CHAIR
References: