rTMS and Rehabilitation for Individuals With CRPS Type 1

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

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.

Study Overview

• Status: Recruiting
• Conditions: Complex Regional Pain Syndrome Type I
• Intervention / Treatment: Device: Repeated Transcranial Magnetic Stimulation; Other: Rehabilitation; Device: Sham Repeated Transcranial Magnetic Stimulation

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adam P Rufa, DPT, PhD; Phone Number: (315)464-6883; Email: rufaa@upstate.edu

Study Locations

• United States
  • New York
    • Syracuse, New York, United States, 13210
      • Recruiting
      • SUNY Upstate Medical Univeristy Institute of Human Performance
      • Contact: Adam p Rufa, DPT, PhD; Phone Number: 315-464-6883; Email: rufaa@upstate.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS and Rehabilitation; Subjects in this arm will get rTMS to the contralateral motor cortex and best practice rehabilitation.	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.; Other Names: rTMS; 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
Sham Comparator: Sham rTMS and Rehabilitation; Subjects in this arm will get sham rTMS to the contralateral motor cortex and best practice rehabilitation.	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; Device: 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 Names: SrTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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.
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).

Collaborators and Investigators

• Sponsor: State University of New York - Upstate Medical University
• Collaborators: Reflex Sympathetic Dystrophy Syndrome Association (RSDSA)
• Investigators: Principal Investigator: Adam Rufa, DPT, PhD, SUNY Upstate Medical Univerity

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy
• Other Study ID Numbers: 1809306-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes