Migraine, rTMS Stimulation
Conditions
Keywords
rTMS neurostimulation
Brief summary
This is a prospective clinical study evaluating the analgesic efficacy of a non-medicated treatment: repeated transcranial magnetic stimulation (rTMS) of the primary motor cortex in chronic migraine (\> 7 headache days per month and failure of at least 3 drug treatments). To this end, the study involves a double-blind, randomized, comparative experimental protocol against a sham control condition via 2 parallel groups comprising 60 patients each (N= 120 in total). Randomized block design with stratification by center and type of migraine (episodic or chronic). 5 rTMS sessions will be performed, with one stimulation session every 2 weeks. One group will receive active stimulation at each session (high-frequency stimulation of the left primary motor cortex, 2000 pulses per session, 80% of resting motor threshold) and the other group placebo stimulation (sham). Depending on the randomization group, rTMS sessions will be carried out by trained experimenters in the investigating center where the patient has been included. The study is multicentric, with five centers, four of which are in the Auvergne-Rhône-Alpes region. Data will be centralized at the Clermont-Ferrand University Hospital, and statistical analysis will be carried out by the Clermont-Ferrand University Hospital's Clinical Research and Innovation Department. Principal difference analysis (active vs sham) performed in ITT; missing data processed by multiple imputation.
Interventions
DEVICErepetitive Transcranial Magnetic Stimulation (rTMS)
robot-guided high-frequency rTMS treatment (10hz - 5 sessions) of the primary motor cortex
DEVICEsham repetitive Magnetic Transcranial Stimulation (rTMS)
sham robot-guided high-frequency rTMS treatment (10hz - 5 sessions) of the primary motor cortex
Sponsors
University Hospital, Clermont-Ferrand
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Age greater than or equal to 18 years ; * Frequent episodic or chronic migraine: migraine more than 8 days per month for more than 3 months; * Maximum 26 headache days / 28 ; * Failure (ineffectiveness, intolerance or contraindication) to at least 3 background drug treatments; * Analgesic treatment stable for at least one month and will not need to be modified for the duration of the study; * Patient can be followed throughout the study; * Information letter read and understood; * Signed informed consent; * Affiliation with a social security scheme.
Exclusion criteria
* Contraindication to rTMS (patient with conductive/sensitive material to magnetic fields implanted in the skull or less than 30 cm from the coil, implanted material controlled by physiological signals, history of epilepsy or unexplained seizures, drug treatment lowering the epileptic threshold, brain lesions in relation to the stimulation zone \[of vascular, traumatic, tumoral, infectious or metabolic origin\], sleep deprivation, alcoholism, treatment with electroconvulsive therapy in the previous month, uncontrolled intracranial hypertension, * Contraindication to MRI (ferromagnetic material not compatible with MRI including: intracerebral metal clip, pacemaker, insulin pump, intrathecal pump, metal prosthesis; severe claustrophobia)§ drug or psychoactive substance abuse * Presence of other pain more severe than that justifying inclusion * Patients under guardianship or deprived of liberty. * Pregnant or breast-feeding women * Patients participating in another research protocol involving a drug in the 30 days prior to inclusion. * Subject having already benefited from rTMS sessions in the past (to maintain the blind)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Variation of headaches days number per month | difference between the 4 weeks prior to initiation of treatment and the last 4 weeks post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| variation in the number of headache (days per month) of at least 50% | between the 4 weeks prior to initiation of treatment and the last 4 weeks post-treatment | — |
| variation in the number of headache (days per month) of at least 30%. | between the 4 weeks prior to initiation of treatment and the last 4 weeks post-treatment | — |
| Patient Global Impression of Change (PGIC) | at week 12 | The score varies from 1 to 7 . A score of 1 means a better outcome and a score of 7 means a worse outcome |
Other
| Measure | Time frame | Description |
|---|---|---|
| Migraine Hypersensitivity Assessment Questionnaire (MHQ-8 scale, ex-MIGAL) score | Pre-treatment period (inclusion visit at W0 - 4) and at week 12 | This scale assesses the frequency and intensity of disturbances related to noise, light, skin stimulation, and odors during migraines |
| Improvement in Quality of life by migraine rescue medication intakes | Week0 - 4 to week0 -1 period compared to Week 9 - week 12 period | Improvement in quality of life will be assessed by use of migraine rescue medication before and after neurostimulation |
| Improvement in Quality of life by European Quality of Life 5 dimensions (EQ- 5D) scale score | At week 0, week 8 and week 12 | Improvement in quality of life will be assessed by the change of EQ-5D score |
| Improvement in Quality of life by relief subjective rate | At Week 2, week 4, week 6, week 8 and week 12 | A relief subjective rate since last neurostimulation will be asked to patient before each new neurostimulation session . A rate of 0% means no relief and 100% means a complete relief . |
| Improvement in Quality of life by anxiety and depression scores | At screening visit (Week 0 - 4) and week 12 | Anxiety and depression will be assessed by Hospital Anxiety and Depression Scale (HADS) |
| Improvement in Quality of life by resilience score | At screening visit (Week 0-4) and week 12 | Resilience score will be assessed by Connor-Davidson Resilience Scale (CD-RISC) in 25 items. The score ranges from 0 to 100 and a higher score means a higher resilience |
| Bang blinding index | week 0, week 2, week 4, week 6, week 8, week 12 | The patient will be asked what he thinks he received after the treatment, rTMS neuromodulation or sham neuromodulation |
| Brain activity (resting-state fMRI) | At screening visit (week 0- 4) and week 12 | MRI recording is routinely carried out before any rTMS session. This involves acquiring a 3D image of the participants' brains, which is necessary for targeting cortical area stimulated by rTMS using a neuronavigation system. Functional imaging (fMRI) in a resting state (i.e., without a 'resting-state' task) will allow to measure the basal state of activity and connectivity in the participants' brains. |
| Cortical excitability | At week 0 and week 12 | measured during rTMS motor threshold with paired pulse stimulation measurements |
| Evaluation of side effects | up to 4 weeks post-treatment (at week 12) | — |
| Changes in prognostic markers of response | At week 0, week 8 and week 12 | Following blood parameters will be assessed : Blood count, CRP, Venous glycemia, Insulin, prolactin, estradiol, FSH, LH, progesterone, testosterone, β-hCG, CGRP, VIP, PACAP-38, IL-6, IL-10, IL-17, IL-18, IL-1α, IL-1β, IL-21, IL-22, IL-23, IL-33, IL-35, CCL-20, IL-36β, IL-37, IL-38, IL-1Ra, TNFa, TGFβ, IL-2, INF-γ, T lymphocyte immunophenotyping (CD3, CD4, CD25, FoxP3, CTLA-4, ICOS, TNFR2, CD45, CD45RA, CD8, CD14, 4-1-BB, NKp46, CD19, CD197, CD39, CD73, GITR, TCRaβ, CD127, CD56, CD62L) |
| Patient Global Impression of Change (PGIC) | week 2, week 4, week 6, week 8 | The score ranges from 1 to 7. A score of 1 means a better outcome and a score of 7 means a worse outcome |
| Improvement in Quality of life by catastrophizing score | At screening visit (Week 0-4) and week 12 | Catastrophism will be assessed by Pain Catastrophizing Scale (PCS) . Score ranges from 0 to 52. A higher score indicates a higher level of catastrophizing of pain. |
| Improvement in Quality of life by intensity and emotional experience of pain | At screening visit (week 0- 4) and week 12 | A visual analogue scale (VAS) ranging from 0 to 100 for pain intensity and affective experience will be used. |
| Variation of blood cytokine levels | Before (Week 0) and after treatment (Weeks 8 and 12) | Following cytokines levels will be assessed : IL-6, IL-10, IL-17, IL-18, IL-1α, IL-1β, IL-21, IL-22, IL-23, IL-33, IL-35, CCL-20, IL-36β, IL-37, IL-38, IL-1Ra, TNFa, TGFβ, IL-2, INF-γ |
| Variation of headaches days number per month | Every each 4-week period post-treatment, compared to 4 weeks before treatment initiation | — |
Countries
France
Contacts
Primary ContactLise LACLAUTRE
Outcome results
None listed