Pragmatic Trial of Remote tDCS and Somatosensory Training for Phantom Limb Pain With Machine Learning to Predict Treatment Response (PLP-EVEREST)

The investigators have designed a pragmatic trial of home-based transcranial direct current stimulation (tDCS) for phantom limb pain (PLP), the PLP-EVEREST trial (PLP-EffectiVEness pRagmatic Stimulation Trial) to test a portable device that would reach underrepresented populations and would validate this therapy in a more pragmatic setting. Subjects will be randomized to home-based tDCS of the primary motor cortex (M1) with somatosensory training or usual care only (including their current pharmacological treatments, physical therapy, and occupational therapy). The investigators will therefore test the effectiveness of home-based tDCS and somatosensory training in a real-world, home-based setting. The Investigator will compare patients randomized to this combined strategy vs. usual care alone (subjects from this group will be offered combined treatment at the end of the trial). The investigators hypothesize that the combined strategy will be associated with a significantly larger Cohen's d effect size (at least 1) compared to the control group.

Study Overview

• Status: Recruiting
• Conditions: Phantom Limb Pain
• Intervention / Treatment: Device: M1 anodal home-based tDCS; Behavioral: Somatosensory Training; Other: Usual Care

Detailed Description

The investigators have designed a pragmatic trial of home-based tDCS for PLP, the PLP-EVEREST trial (PLP-EffectiVEness pRagmatic Stimulation Trial) to test a portable device that would reach underrepresented populations and would validate this therapy in a more pragmatic setting. Subjects will be randomized to home-based tDCS of the M1 with somatosensory training or usual care only (including their current pharmacological treatments, physical therapy, and occupational therapy). The investigators will therefore test the effectiveness of home-based tDCS and somatosensory training in a real-world, home-based setting. The investigator will compare patients randomized to this combined strategy vs. usual care alone (subjects from this group will be offered combined treatment at the end of the trial). The investigators hypothesize that the combined strategy will be associated with a significantly larger Cohen's d effect size (at least 1) compared to the control group.

The investigators will perform a pragmatic, parallel randomized clinical trial. Investigators will recruit 290 participants with upper and/or lower bilateral or unilateral limb amputation and phantom limb pain in the chronic phase. All participants will be randomized to receive 20 daily sessions (4 weeks) of active anodal M1 home-based tDCS combined with somatosensory training or usual care. The participants will participate in 23 visits over 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 290
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Felipe Fregni, MD, PhD, MPH, MMSc; Phone Number: 617-952-6158; Email: ffregni@partners.org
• Study Contact Backup: Name: Kevin Pacheco-Barrios, MS, MSc, MPH; Phone Number: 617-952-6195; Email: kpachecobarrios@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02138
      • Recruiting
      • Spaulding Hospital Cambridge
      • Contact: Elly Pichardo, MD; Phone Number: 6179526158; Email: epichardo@partners.org
      • Principal Investigator: Felipe Fregni, MD, PhD, MMSc, MPH, MEd

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age - older than 18 years
2. Limb amputation
3. Patients who experience PLP regularly (at least once a week)
4. Pain not attributable to other causes, such as peripheral inflammation
5. Current chronic pain as defined by an average pain of at least 4 on the numeric rating scale (NRS, 0: no pain, 10: worst imaginable pain)

Exclusion Criteria:

1. Any clinically significant or unstable medical or psychiatric disorder
2. History of substance abuse in the past 6 months (according to the DSM-V criteria for substance use disorder with six or more symptoms)
3. Uncompensated psychiatric disorder
4. Previous significant neurological history with current significant neurological deficits
5. Previous neurosurgical procedure with craniectomy that would affect current distribution of tDCS
6. Contraindications to tDCS (implanted brain medical devices)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M1 anodal home-based tDCS and somatosensory training; Investigators will use the Soterix Medical 1X1 tDCS mini-CT stimulator device (© Soterix Medical Inc.) an home-based tDCS device used in several clinical trials with no adverse events. It sends a low-level current from the positive electrode, anode, to the negative electrode, cathode. During tDCS, low amplitude direct currents are applied via scalp electrodes and penetrate the skull to enter the brain. HB-TDCS will be combined with somatosensory training that will be performed during the self-administration of tDCS, including 20 sessions over 4 weeks.	Device: M1 anodal home-based tDCS; During tDCS, low amplitude direct currents are applied via scalp electrodes and penetrate the skull to enter the brain. Direct current will be transferred by a saline-soaked pair of surface sponge electrodes (35 cm2) and delivered by a specially developed, battery-driven, constant current stimulator with a maximum output of 10 mA.; Behavioral: Somatosensory Training; The somatosensory training will be performed during the self-administration of tDCS, including 20 sessions over 4 weeks. Sessions will start with relaxation exercises using a body scan technique, whereby subjects in a relaxed state will be instructed to sequentially interchange their mind to different regions of the body while perceiving it and establishing contact with the body part. Subjects will be asked to concentrate on any feeling (kinetic, kinesthetic or exteroceptive) related to each body part. Phantom exercises will involve the use of imagined movements of the phantom limb. Therefore, patients will be asked to perform general exercises with their phantom limb. Exercises will include hip, knee, ankle, and toe movements.
Experimental: Usual Care; Usual care includes pharmacological treatments, physical therapy, occupational therapy and/or behavioral therapy that the subject is receiving.	Other: Usual Care; Usual care includes pharmacological treatments, physical therapy, occupational therapy and/or behavioral therapy that the subject is receiving.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale (VAS) for Phantom Limb Pain	The VAS is a common assessment that asks subjects to self-reportedly measure their pain on a visual scale (i.e., unbearable to none). Investigators will use the VAS to determine subjects' pain scores. Subjects will rate their pain from 0 - indicating no pain at all, to 10 - indicating the worst pain felt. This scale is also colored, from green (at 0) to red (at 10), as a visual indicator of pain. This assessment tool is frequently used in many research studies evaluating pain levels in phantom limb.	From Baseline to Visit 22 (at 4 weeks)

Collaborators and Investigators

• Sponsor: Spaulding Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Pain, Postoperative; Phantom Limb
• Other Study ID Numbers: 2021P003323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon completion of the trial and after publication of the primary manuscript, the investigators plan to publish the de-identified dataset following the guidelines of our institution (Spaulding Rehabilitation Hospital/Partners Healthcare and Harvard Medical School).

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