Preventing Chronification of Phantom Limb Pain Through Mirror Therapy in Conjunction With tDCS

NCT07139483 | Recruiting

• 1 other identifier: 253/23
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

Brief Summary

Background: Most amputees experience phantom limb pain (PLP), for years after amputation. Virtually all PLP research to date has focused on the mechanisms of chronic PLP, ignoring the mechanisms of chronification. This research project will focus on combined neuromodulatory interventions of mirror therapy (MT) and trans direct-cranial stimulation (tDCS), applied for the first time at the acute state of PLP, with an aim to prevent its chronification and chronicity. In PLP, maladaptive plasticity associated with sensory deafferentation following an amputation is one of the contributors for excessive pain. MT is a well-accepted yet limited option, which is thought to counterbalance abnormal plasticity. tDCS is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. The researchers' objectives are to investigate whether the combined therapy of MT and tDCS will prevent chronic PLP and improve its related clinical characteristics. In addition, the researchers will investigate the behavioral manifestations effects of the combined treatment. The investigators expect that the combined treatment applied at the acute stage of PLP will have synergistic effects on PLP intensity and thus avert its chronification. In addition, it will reduce phantom sensations, and negative affect, and will improve the sense of body ownership and agency and endogenous inhibition efficiency. Research design: This randomized-controlled double-blinded study will be held at Israel's 3 largest rehabilitation centers. The study consists of 3 randomized patient arms (36 in each): (1) no-intervention, natural-course group; (2) MT + sham tDCS; (3) MT + real tDCS. MT and tDCS neuromodulatory interferences will be self-administered and consist of 20 sessions, completed during 4 weeks. The researchers outcome measures include: primary outcome: pain intensity, network-related behavioral markers, and amputation-related clinical characteristics. The data gathered will be collected at 5 timepoints. Research novelty and innovation: The researchers proposed model will provide insights on the prevention of PLP and, potentially, other neurological pathologies involving the dysfunction of sensory systems and integration and body perception.

Conditions

Phantom Limb Pain After Amputation

Keywords

PLP; Phantom sensation; telescoping; amputation; tDCS; MT; Maladaptive plasticity; Phantom Limb Pain

Outcome Measures

Primary Outcomes (1)

• A 0-100 VAS of mean pain intensity during one week

  completed during 7 days, will be used to capture the weekly average of pain intensity (0 = no pain to 100 = the worst imaginable pain, via pain diary). This data will be used either in its raw, continuous form or as a transformed dichotomous variable, yes/no chronic PLP. A cutoff value of PLP intensity ≤20/100 will be used, because from a clinical perspective, pain intensity ≤20 is considered low and will seldom prompt a request for analgesic treatment.

  Pain will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

Secondary Outcomes (8)

• Sense of ownership and agency over phantom limb

  Sense of ownership and agency over phantom limb will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

• The Hospital Anxiety and Depression Scale (HADS)

  Anxiety and Depression will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

• The Short Form McGill Pain Questionnaire

  The Affective qualities of pain will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

• The Conditioned Pain Modulation (CPM)

  The CPM score will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

• Frequency of PLP paroxysms

  Frequency of PLP paroxysms will be compared between baseline and 4 weeks after the end of the 4 weeks intervention (meaning, comparing baseline to timepoint number 3, which is exactly 8 weeks from the end of the baseline week)

Study Arms (3)

Mirror Therapy + real tDCS

ACTIVE COMPARATOR

Both MT and tDCS neuromodulatory interferences (separately or combined) will consist of 20 sessions, each lasting 20 min, completed during 4 weeks, once daily (excluding weekends). The neuromodulatory interferences will be self-administered by the participants. The first 2 sessions (at the clinic) will include training to familiarize participants (and their primary caregivers) with the procedure and to instruct them on the self-administering techniques that the researchers and others successfully employed. After training, neuromodulatory interferences will be applied either at the clinic (during hospitalization) or at home (after discharge). This approach promotes participants' retention and reduces dropouts, especially when the study constitutes multiple sessions.

Device: Trans Direct-Cranial Stimulation (tDCS); Behavioral: Mirror therapy

Mirror Therapy + sham tDCS

SHAM COMPARATOR

Both MT and tDCS neuromodulatory interferences (separately or combined) will consist of 20 sessions, each lasting 20 min, completed during 4 weeks, once daily (excluding weekends). The sham tDCS will be identical to the real tDCS, except no current will be applied. However, as recommended, during the first and last 30 sec, the current will be ramped up to 1.5 mA and immediately back to 0 to induce scalp sensations similar to those in real tDCS, further supporting blinding

Device: Trans Direct-Cranial Stimulation (tDCS); Behavioral: Mirror therapy

No-intervention, natural-course group

NO INTERVENTION

The participants will receive the regular treatment regimen at the rehabilitation center, including physical-therapy and pharmacological treatment, without intervention of Mirror-therapy and tDCS.

Interventions

Trans Direct-Cranial Stimulation (tDCS) DEVICE

The tDCS electrodes will be inserted into 5×7 cm (35 cm2) sponges soaked with saline (0.9 M) and placed as follows: anode over the M1 contralateral to the amputated limb (adjusted based on lower/upper amputation), and cathode over the forehead, contralateral to the anode (ipsilateral to amputated limb). Total stimulation duration will be 20 min, with a rise and decline time of 30 sec and stimulus intensity of 1.5 mA for the real tDCS real. The intensity of 1.5 mA is in the midrange of recommended intensities (1-2 mA) and supports successful blinding. The sham tDCS will be identical to the real tDCS, except no current will be applied. However, as recommended, during the first and last 30 sec, the current will be ramped up to 1.5 mA and immediately back to 0 to induce scalp sensations similar to those in real tDCS, further supporting blinding. The Mini-CT tDCS Stimulator device has been developed for home use and allows double-blind administration.

Mirror Therapy + real tDCS; Mirror Therapy + sham tDCS

Mirror therapy BEHAVIORAL

Participants will be seated with a portable mirror between their limbs so that the unaffected limb is reflected in the mirror. The participants will focus their attention on the reflection in the mirror and perform the following movements: plantarflexion and dorsiflexion and inversion and eversion of the foot, flexion and extension of the wrist and ulnar and radial deviation, for lower and upper limp amputates, respectively. The participants will continue performing the 2 sets of movements for 20 minutes (with short intermissions if needed)

Mirror Therapy + real tDCS; Mirror Therapy + sham tDCS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (age ≥18);
• Amputation of a single limb ≤12 weeks ago; during this period of time, 80% of amputees develop PLP. Both upper and lower limb amputees are included to increase feasibility;
• Acute PLP stage (2 weeks since first report), with intensity ≥3 on a 0-10 VAS;
• No change in medication in past week, excluding pro re nata analgesics;
• Can understand the study's purpose and instructions;
• Agrees to participate and to provide written informed consent.

You may not qualify if:

• Stump wound not healed;
• Other psychological, psychiatric, or neurological conditions;
• Contraindications for tDCS or magnetic resonance imaging (MRI) (MRI data will not be analyzed in the proposed PhD project), including previous seizure, loss of consciousness due to head injury, metal in the head, implanted devices, claustrophobia, a skin condition or an unhealed wound on the scalp, and possibility of being pregnant;
• Inability to provide informed consent or understand or carry out the experiment.

Sponsors & Collaborators

• University of Haifa: lead
• Loewenstein Hospital: collaborator
• Reuth Rehabilitation Hospital: collaborator
• Sheba Medical Center: collaborator

Study Sites (3)

Loewenstein Hospital

Raanana, Israel, Ahuza 278, Israel

RECRUITING

Reut Medical Center

Tel Aviv, Israel, Israel

RECRUITING

Sheba Medical Center

Tel Aviv, Israel

NOT YET RECRUITING

MeSH Terms

Conditions

Phantom Limb

Interventions

Mirror Movement Therapy

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Intervention Hierarchy (Ancestors)

Physical Therapy Modalities; Rehabilitation; Therapeutics

Study Officials

• Roi Treister, PhD

  University of Haifa Faculty of Social Welfare and Health Sciences

  STUDY DIRECTOR

Central Study Contacts

Roi Treister, PhD

CONTACT

+972533839935; rtreister@univ.haifa.ac.il

Shlomit Sorek, BPT MPT

CONTACT

+972-0507324111; sorekshlomit@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study consists of 2 main parallel participants groups: traumatic and a-traumatic. Upon their arrival at the rehabilitation centers, participants will be recruited, give consent, and receive a serial number. Only patients developing PLP will be randomly assigned to the study arms. There will be 3 randomized patient arms (for each participants group): (1) no-intervention, natural-course group; (2) MT + sham tDCS; (3) MT + real tDCS . Therefore, the proposed project is a randomized, controlled, double blind, multicenter study. Further, the personnel collecting the data will be fully blinded to group assignments. The data will be collected at 5 timepoints during the experiment. Each timepoint will comprise 1 week of assessments: T1 (baseline week), before the 4 weeks of neuromodulatory application; T2, immediately after the end of the application; and T3, T4, and T5, assessments conducted 1, 3, and 6 months, respectively, after the end of the neuromodulatory application

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: August 24, 2025
• Study Start: March 25, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (3)