An interventional study of Sham nrTMS and open phase and Active nrTMS and open phase in Transcranial Magnetic Stimulation and Complex Regional Pain Syndrome of Upper Limb (Disorder), sponsored by Helsinki University Central Hospital. Completed at 2 sites in Finland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-03.
Sponsored by Helsinki University Central Hospital · Not applicable, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Active nrTMS is given to "S2" at the right side (10 sessions in a three week period). Thereafter, a new, open label phase will start if the average pain at 3 month follow-up is ≥5/10. Then, the nrTMS will be targeted to M1 contralateral to the side of pain. After 5 stimulation sessions the response is evaluated. If pain is still ≥510, the investigators change the target to the "S2" on the left side for five sessions. If there is response with pain relief, a maintenance therapy with this target is offered for 6 months with gradually reducing stimulation sessions.
Device: Active nrTMS and open phase
Sham nrTMS will be targeted to the "S2" on the right side, but using a sham box/coil. Stimulation period is similar than for the active comparator. Similarly, thereafter, a new, open label phase will start if the average pain at 3 month follow-up is ≥5/10. Then, the nrTMS will be targeted to "S2" at the right side. After 5 stimulation sessions the response is evaluated. If pain is still ≥5/10, the investigators change the target to M1 on the contralateral side of the pain and furthermore to "S2" at the left side after 5 stimulation sessions, if pain is still ≥5/10.
Device: Sham 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".
Also known as: Starts with sham stimulation
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".
Also known as: Starts with active stimulation
15-item quality of life measure
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.
Time frame: Change from baseline at one month
Mean pain intensity and interference
Numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable)
Time frame: Baseline, during stimulation, and two weeks after the intervention
Weekly pain intensity and interference
Pain questionnaires (numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable)
Time frame: Up to 3 months after intervention
Sleep interference and quality
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.
Time frame: Baseline and 1,2,and 3 months after intervention
Clinical neurophysiology measures
Quantitative sensory testing (QST) with standardized reporting
Time frame: Baseline and one week after intervention
Cognitive assessment A
Cognitive function assessment by Cogstate, a computer based detection and identification task. Answers yes or no, standard reporting.
Time frame: Baseline and one month after the intervention
Hand strength
Hand motor function measured e.g. by Jamar (kg)
Time frame: Baseline and one week after the intervention.
Biochemical tests
Blood samples: inflammatory markers (e.g. high sensitivity CRP, proteomics). Standard reporting
Time frame: At baseline
Brain imaging: Default mode networks
Resting state fMRI
Time frame: Baseline and one week after intervention
CRPS symptom severity
CRPS severity scale (CSS, 0=no symptoms or signs, 17=maximum score with symptoms and signs)
Time frame: Baseline and at one month
Patient global impression of change
Global impression of change (GIC, 1=very much improved, 7= very much worse)
Time frame: 1, 2, and 3 months and through study completion, an average of 1 year
Screening of psychiatric symptoms and diagnostics
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.
Time frame: Up to 24 weeks
Hand mobility
Angles of the joints in the hand (degrees)
Time frame: Baseline and one week after intervention
Cognitive assessment B
Wechsler Memory Scale III (WMS-III) subtest: digit span. Number of digits recalled. Standard reporting.
Time frame: Baseline and one month after the intervention
Cognitive assessment C
Wechsler Memory Scale III (WMS-III) subtest: word list. Number of words recalled. Standard reporting.
Time frame: Baseline and one month after the intervention
Cognitive assessment D
Bourdon-Wiersma (Attention and concentration): number of visual stimuli found.
Time frame: Baseline and one month after the intervention
Cognitive assesment E
Trail-Making Test (Parts A and B): time spent (seconds) for visual scanning task. Standard reporting.
Time frame: Baseline and one month after the intervention
DNA
DNA analysis. Standard reporting.
Time frame: At baseline
Plan to share: No — The Ethics committee doesn't allow that due to privacy agreements.
This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Complex Regional Pain Syndromes→
Helsinki University Central Hospital