rTMS and Rehabilitation for Individuals With CRPS Type 1

Complex Regional Pain Syndrome Type I Clinical Trial

Official title:

Repeated Transcranial Magnetic Stimulation and Rehabilitation for Individuals With Complex Regional Pain Syndrome Type 1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05745025
• Other study ID #: 1809306-4
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2023
• Est. completion date: August 1, 2025

Study information

• Verified date: August 2023
• Source: State University of New York - Upstate Medical University
• Contact: Adam P Rufa, DPT, PhD
• Phone: (315)464-6883
• Email: rufaa[@]upstate.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Subjects with complex regional pain syndrome (CRPS) Type 1 will be randomized to receive repeated transcranial magnetic stimulation (rTMS) followed by rehabilitation or sham rTMS followed by rehabilitation. Treatment will last for 4 weeks, with the first week including 4 rTMS treatments and 2 rehabilitation treatments. Subsequent weeks will include 2 rTMS treatments followed by 2 rehabilitation treatments. Outcome measures will include pain ratings, PROMIS questionnaires, global rating of change, and grip strength or 1 repetition maximum leg press.

Description:

Subjects will be randomized to receive either real or sham rTMS, combined with rehabilitation. Subjects will attend 10 sessions over 4 weeks. rTMS will be delivered at 10Hz using an intensity of 80% of the motor threshold. Pulse trains will be delivered for 10 seconds, with a 30-second rest for 20 repetitions. This will result in a total of 2,000 pulses of magnetic stimulation and will take approximately 20 minutes. There will be 10 rTMS sessions over the 4 weeks. Sham rTMS will be delivered using the same method as rTMS, but a sham coil, that does not deliver magnetic stimulation, will be used. Rehabilitation will include graded motor imagery, education, and graded functional activity. There will be 8 rehabilitation sessions over 4 weeks. Outcomes will include questionnaires asking about pain and function, and either grip strength or leg press strength measurements.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Upper or lower extremity CRPS Type 1 (also called RSD-Reflex Sympathetic Dystrophy) of at least 6 months.
• Pain rating on NPRS of at least 4/10
• No initiation of a new intervention (i.e., medication, rehab, injections) in the previous 2 months.
• No plan to initiate a new intervention during the study treatment timeframe (4 weeks).

Exclusion Criteria:

• A history of seizures or epilepsy
• Intracranial metallic devices
• Pacemaker
• Intrathecal infusion pumps
• Brain or spinal cord stimulators with epidural electrodes
• Other ferromagnetic metallic intracranial implants
• Apparent mental or psychiatric disorder that prevents adequate informed consent
• Current pregnancy
• Non-English speaking

Related Conditions & MeSH terms

• Complex Regional Pain Syndrome Type I
• Complex Regional Pain Syndromes
• Reflex Sympathetic Dystrophy
• Syndrome

Intervention

Device:
• Repeated Transcranial Magnetic Stimulation
rTMS will be delivered using a commercially available magnetic stimulator (Rapid2, Magstim Inc., Eden Prairie, MN) with a figure-of-8 Air Film coil at 10 Hz. Coil orientation will be optimized for stimulation of the abductor pollicis brevis. Stimulation targeting will be identified using motor-evoked potentials (MEP) of the first dorsal interossei that will be monitored using electromyography (EMG) (Motion Lab Systems Inc., Baton Rouge, LA). The motor threshold (MT) of the muscle will then be identified by systematically adjusting the pulse intensity. The MT will be considered the lowest stimulation intensity at which 5 out of 10 MEPs have a peak-to-peak amplitude of at least 50 microvolts. rTMS will be performed at the identified optimal location at 10Hz using an intensity that is 80% of the MT. Pulse trains will be delivered for 10 seconds, with a 30-second rest for 20 repetitions.
• Sham Repeated Transcranial Magnetic Stimulation
Sham rTMS will be performed using the same methods as the active group, but a sham Air Film coil (Magstim Inc., Eden Prairie, MN) will be used. This coil looks and sounds like the active coil, but it does not deliver magnetic pulses.

Other:
• Rehabilitation
Rehabilitation will consist of education, value-based goal setting, Graded Motor Imagery (GMI) (3 components described below), and graded activity. Subjects will complete activities at treatment sessions and be asked to perform certain treatment activities at home. Week 1: Pain education, functional value-based goal setting, laterality training (first component of GMI), one task for graded activity (task-based on patient goals) Week 2: Continue week 1 activity, add graded motor imagery (second component of GMI), progress 1st graded activity, and initiate 2nd graded activity exercise. Week 3- Mirror therapy (third component of GMI), assess knowledge and update education as needed, progress graded activity 1 and 2, and add 3rd graded activity if appropriate based on patient goals. Week 4- Continue with week 3 activities. Discuss experience with meditation and progress graded activity as tolerated

Locations

Country	Name	City	State
United States	SUNY Upstate Medical Univeristy Institute of Human Performance	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
State University of New York - Upstate Medical University	Reflex Sympathetic Dystrophy Syndrome Association (RSDSA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Eldufani J, Elahmer N, Blaise G. A medical mystery of complex regional pain syndrome. Heliyon. 2020 Feb 19;6(2):e03329. doi: 10.1016/j.heliyon.2020.e03329. eCollection 2020 Feb. — View Citation

Gaertner M, Kong JT, Scherrer KH, Foote A, Mackey S, Johnson KA. Advancing Transcranial Magnetic Stimulation Methods for Complex Regional Pain Syndrome: An Open-Label Study of Paired Theta Burst and High-Frequency Stimulation. Neuromodulation. 2018 Jun;21(4):409-416. doi: 10.1111/ner.12760. Epub 2018 Mar 4. — View Citation

Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipovic SR, Grefkes C, Hasan A, Hummel FC, Jaaskelainen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, Palm U, Paulus W, Poulet E, Quartarone A, Rachid F, Rektorova I, Rossi S, Sahlsten H, Schecklmann M, Szekely D, Ziemann U. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018). Clin Neurophysiol. 2020 Feb;131(2):474-528. doi: 10.1016/j.clinph.2019.11.002. Epub 2020 Jan 1. Erratum In: Clin Neurophysiol. 2020 May;131(5):1168-1169. — View Citation

Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolin MA. Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain. 2010 Nov;11(11):1203-10. doi: 10.1016/j.jpain.2010.02.006. Epub 2010 Apr 28. — View Citation

Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M. Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. Neurosci Lett. 2004 Feb 12;356(2):87-90. doi: 10.1016/j.neulet.2003.11.037. — View Citation

Shafiee E, MacDermid J, Packham T, Walton D, Grewal R, Farzad M. The Effectiveness of Rehabilitation Interventions on Pain and Disability for Complex Regional Pain Syndrome: A Systematic Review and Meta-analysis. Clin J Pain. 2023 Feb 1;39(2):91-105. doi: 10.1097/AJP.0000000000001089. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numeric Pain Rating Scale (NPRS) Weekly Average	Subjects will be asked to rate their weekly average pain on a scale from 0-10 (0 indicating no pain and 10 indicating worse possible pain).	Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session.
Secondary	Numeric Pain Rating Scale (NPRS) worse/least pain over 24 hours	Subjects will be asked to rate their highest pain level and lowest pain level over a 24-hour period. (0 indicating no pain and 10 indicating worse possible pain).	Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session
Secondary	Patient-Reported Outcomes Measurement Information Systems (PROMIS).	NIH developed computer adaptive tools measuring pain interference, pain behavior, physical functioning, social roles, fatigue, depression, anxiety, and anger. Scores are reported based on T-scores with a mean population score of 50 and a standard deviation of 10. Scores generally range from 20-80. For symptom scales (i.e. pain interference), higher scores indicate worse symptoms, and for function scales (i.e. social roles), higher scores indicate better function.	Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session
Secondary	Global Rating of Change (GROC)	Subjects will be asked to rate the change of their symptoms from 7(a great deal better) to -7 (a great deal worse) with 0 being no different.	Sessions 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session
Secondary	Global Rating of Change Impact (GROCi)	Subjects will be asked to rate the impact of the change from 7(a great deal better) to -7 (a great deal worse) with 0 being no different.	Sessions 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4) Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session
Secondary	Patient Acceptable Symptom State (PASS)	Patients are asked if their current state of symptoms is acceptable, yes/no	Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4). Surveys will also be sent at 4 weeks, 3 months, 6 months, and 1 year after last session.
Secondary	Grip Strength or 1 Rep Leg Press	Subjects with upper extremity involvement will have grip strength measured using a dynamometer. Subjects with lower extremity involvement will be tested with single leg 1 rep max leg press.	Sessions 1 (week 1), 4 (week 1), 6 (week 2), 8 (week 3), 10 (week 4).