Complex Regional Pain Syndrome of Upper Limb (Disorder), Transcranial Magnetic Stimulation
Conditions
Keywords
TMS, CRPS, pain, fMRI, quality of life, mood, cognitive function, DNA
Brief summary
This is a sham controlled, randomized, double-blind, navigated repetitive Transcranial Magnetic Stimulation (nrTMS) study for the treatment of complex regional pain syndrome (CRPS types 1 and 2). The investigators study factors that may contribute to development, maintenance, or treatment responses with clinical, sleep, and psychiatric questionnaires and clinical examinations, quantitative sensory testing and neurophysiologic recordings, genetics, and MRI techniques.
Detailed description
rTMS hypothetically disrupts the default networks related to chronic pain and renders the brain more susceptible to drugs, rehabilitation, or cognitive behavioral therapy. In addition, there is experimental evidence that rTMS releases factors that are involved in endogenous top-down modulation of pain and neural plasticity. Thus, the analgesic effect of rTMS may be mediated via enforcing endogenous pain control systems at the brain level, in addition to its effects on neuroplastic effects. For active, navigated stimulation targets the investigators have the parietal opercular cortex overlying the secondary somatosensory cortex (S2) and the primary motor cortex (M1). The investigators randomize participants to first receive nrTMS to the right S2 or sham stimulation. After ten sessions the investigators follow up the participants up to three months. At three months, if the average pain is ≥5/10 in numeric rating scale (NRS), the participant is offered an active, open nrTMS treatment phase depending on which treatment the participant first received. If the participant benefits from the open label treatment, a maintenance therapy is offered (6 months with gradually reducing nrTMS treatment frequency). The symptoms and quality of life are followed with questionnaires and diaries. After the maintenance period, the RN calls a structured interview at 1, 3, and 6 months.
Interventions
DEVICESham nrTMS and open phase
Navigated repetitive TMS treatment (10 sessions during a three-week period) randomized to sham. In the following open phase stimulation the treatment targets are the right S2-contralateral M1-left S2.
DEVICEActive nrTMS and open phase
Navigated repetitive TMS treatment (10 sessions during a three-week period) randomized to S2. In the following open phase stimulation the treatment targets are contralateral M1 and left S2. If the patient benefited from active S2 stimulation, but the treatment effect faded in follow-up, the open phase stimulation starts with right S2.
Sponsors
Turku University Hospital
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The participant does not know whether the stimulation is sham or active. The doctor or nurse giving the stimulation knows the target and whether the stimulation is sham or active. The RN and the clinician (conducting screening and 1 month clinical visit) do not know the stimulation type or target until month 3, when the code is opened.
Intervention model description
The patients are first randomized to receive either sham stimulation or right S2 for three week period (10 stimulation sessions). Thereafter, a 3 month followup period (clinical checkup at a research visit at 1 month, RN structured telephone interviews at 2 and 3 months). If pain ≥5/10 at 3 month interview, the patient is offered an open label nrTMS treatment phase, in which the protocol depends on the first protocol of the RCT phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* CRPS 1 or 2 of the upper limb * Duration ≥ 6 months * Mean pain (NRS) intensity ≥5/10 * Medical and other therapies have failed
Exclusion criteria
* Other stimulation therapies apart from transcutaneous nerve stimulation * psychotic disorder * severe depression * use of strong opioids * epilepsy * any contraindication for MRI * abuse of alcohol or drugs * ongoing insurance or other entitlement cases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 15-item quality of life measure | Change from baseline at one month | Quality of life (15D questionnaire) with 15 question items with 5 alternatives in each. The scores range between 15 to 75 with 15 the best and 75 the worst quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weekly pain intensity and interference | Up to 3 months after intervention | Pain questionnaires (numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable) |
| Sleep interference and quality | Baseline and 1,2,and 3 months after intervention | Insonnia severity index (ISI). There are seven questions with scale 0 to 4 (0 with no symptoms and 4 with the worst symptoms). The scores are added up to get a total score ranging from 0 to 28. A higher score means a worse outcome. |
| Clinical neurophysiology measures | Baseline and one week after intervention | Quantitative sensory testing (QST) with standardized reporting |
| Cognitive assessment A | Baseline and one month after the intervention | Cognitive function assessment by Cogstate, a computer based detection and identification task. Answers yes or no, standard reporting. |
| Hand strength | Baseline and one week after the intervention. | Hand motor function measured e.g. by Jamar (kg) |
| Biochemical tests | At baseline | Blood samples: inflammatory markers (e.g. high sensitivity CRP, proteomics). Standard reporting |
| Brain imaging: Default mode networks | Baseline and one week after intervention | Resting state fMRI |
| CRPS symptom severity | Baseline and at one month | CRPS severity scale (CSS, 0=no symptoms or signs, 17=maximum score with symptoms and signs) |
| Mean pain intensity and interference | Baseline, during stimulation, and two weeks after the intervention | Numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable) |
| Screening of psychiatric symptoms and diagnostics | Up to 24 weeks | Psychiatric interveiw (SCID II) with symptom and diagnostic description. Nine questions, answers yes or no, standard reporting. The more yes-answers, the worse the outcome. |
| Hand mobility | Baseline and one week after intervention | Angles of the joints in the hand (degrees) |
| Cognitive assessment B | Baseline and one month after the intervention | Wechsler Memory Scale III (WMS-III) subtest: digit span. Number of digits recalled. Standard reporting. |
| Cognitive assessment C | Baseline and one month after the intervention | Wechsler Memory Scale III (WMS-III) subtest: word list. Number of words recalled. Standard reporting. |
| Cognitive assessment D | Baseline and one month after the intervention | Bourdon-Wiersma (Attention and concentration): number of visual stimuli found. |
| Cognitive assesment E | Baseline and one month after the intervention | Trail-Making Test (Parts A and B): time spent (seconds) for visual scanning task. Standard reporting. |
| DNA | At baseline | DNA analysis. Standard reporting. |
| Patient global impression of change | 1, 2, and 3 months and through study completion, an average of 1 year | Global impression of change (GIC, 1=very much improved, 7= very much worse) |
Countries
Finland
Outcome results
None listed