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NCT Number: NCT04439669

CRPS - Diagnostics, Pathophysiological Mechanisms, and Response to Treatment With Noninvasive Brain Stimulation

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.

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Key information

Conditions

Transcranial Magnetic Stimulation Autonomic Nervous System Diseases Complex Regional Pain Syndrome of Upper Limb (Disorder) Complex Regional Pain Syndromes Nervous System Diseases Neurologic Manifestations Neuromuscular Diseases Pain Pathological Conditions, Signs and Symptoms Peripheral Nervous System Diseases Reflex Sympathetic Dystrophy Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Turku University Hospital, Pain Clinic, Turku, Southwest Finland, Finland

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sham nrTMS and open phase

Device

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".

Other names: Starts with sham stimulation

Active nrTMS and open phase

Device

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".

Other names: Starts with active stimulation

Primary outcomes

  1. 15-item quality of life measure

    Time frame: 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 outcomes

  1. Mean pain intensity and interference

    Time frame: Baseline, during stimulation, and two weeks after the intervention

    Numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable)

  2. Weekly pain intensity and interference

    Time frame: Up to 3 months after intervention

    Pain questionnaires (numeric rating scale (NRS, 0= no pain and 10= the worst pain imaginable)

  3. Sleep interference and quality

    Time frame: 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.

  4. Clinical neurophysiology measures

    Time frame: Baseline and one week after intervention

    Quantitative sensory testing (QST) with standardized reporting

  5. Cognitive assessment A

    Time frame: 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.

  6. Hand strength

    Time frame: Baseline and one week after the intervention.

    Hand motor function measured e.g. by Jamar (kg)

  7. Biochemical tests

    Time frame: At baseline

    Blood samples: inflammatory markers (e.g. high sensitivity CRP, proteomics). Standard reporting

  8. Brain imaging: Default mode networks

    Time frame: Baseline and one week after intervention

    Resting state fMRI

  9. CRPS symptom severity

    Time frame: Baseline and at one month

    CRPS severity scale (CSS, 0=no symptoms or signs, 17=maximum score with symptoms and signs)

  10. Patient global impression of change

    Time frame: 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)

  11. Screening of psychiatric symptoms and diagnostics

    Time frame: 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.

  12. Hand mobility

    Time frame: Baseline and one week after intervention

    Angles of the joints in the hand (degrees)

  13. Cognitive assessment B

    Time frame: Baseline and one month after the intervention

    Wechsler Memory Scale III (WMS-III) subtest: digit span. Number of digits recalled. Standard reporting.

  14. Cognitive assessment C

    Time frame: Baseline and one month after the intervention

    Wechsler Memory Scale III (WMS-III) subtest: word list. Number of words recalled. Standard reporting.

  15. Cognitive assessment D

    Time frame: Baseline and one month after the intervention

    Bourdon-Wiersma (Attention and concentration): number of visual stimuli found.

  16. Cognitive assesment E

    Time frame: Baseline and one month after the intervention

    Trail-Making Test (Parts A and B): time spent (seconds) for visual scanning task. Standard reporting.

  17. DNA

    Time frame: At baseline

    DNA analysis. Standard reporting.

Sponsors and collaborators

Lead sponsor

Helsinki University Central Hospital

Other

Collaborators

  • Turku University Hospital

Registry information

Official study title

Complex Regional Pain Syndrome - Diagnostics, Pathophysiological Mechanisms, and Response to Treatment With Noninvasive Brain Stimulation

Important dates

Study start
2017
Primary completion
2021
Study completion
2022
First posted
Jun 19, 2020
Registry last updated
Jul 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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