Neuromodulation in Patients With Neuropathic Pain and Depression. (DOLODEP)

Neuromodulation in Patients With Neuropathic Pain and Depression: a Cross-over Study Between Two Targets in Transcranial Magnetic Stimulation, the Primary Motor Cortex and the Dorsolateral Prefrontal Cortex.

High-frequency repetitive transcranial magnetic stimulation of the primary motor cortex has shown its effect on refractory neuropathic pain, and rTMS of the dorsolateral prefrontal cortex is commonly used for treatment-resistant depression.

The treatment for patients suffering from neuropathic pain and depression, concomitantly, still needs to be studied, as there are some specificities in both symptoms and brain functional MRI.

Study Overview

• Status: Recruiting
• Conditions: Depression; Neuropathic Pain
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation (rTMS) - M1/DLPFC; Device: Repetitive transcranial magnetic stimulation (rTMS) - DLPFC/M1

Detailed Description

This project is a cross-over study for these patients, including 4 sessions of either M1 or DLPFC rTMS, a wash-out period, followed by 4 sessions of the other stimulation site, to assess the efficiency of a DLPFC rTMS for neuropathic pain with a comorbid depression. Besides pain intensity and quality, patient's mood, quality of life, and catastrophizing will be assessed.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hélène RAINGARD, CRA; Email: helene.raingard@chu-st-etienne.fr
• Study Contact Backup: Name: Roland PEYRON, PhD; Phone Number: +33 (0)4 77 12 78 05; Email: Roland.Peyron@univ-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France, 42055
    • Recruiting
    • CHU de Saint-Etienne
    • Contact: Roland PEYRON, PhD; Phone Number: +33 (0)4 77 12 78 05; Email: Roland.Peyron@univ-st-etienne.fr
    • Principal Investigator: Roland PEYRON, PhD
    • Sub-Investigator: Christelle CREACH, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Central or peripheral neuropathic pain
• Chronic pain (present for more than 6 months) with intensity greater than or equal to 4/10 on the numerical scale
• Pain present on a daily or near-daily basis (at least 4 days a week)
• Patient not completely relieved by recommended drug treatments for first- and second-line neuropathic pain
• Stable analgesic treatment (no new treatment or dosage adjustment) for at least one month, and will not need to be modified for the duration of the study.
• Patient with a depressive episode characterized according to DSM V criteria
• Indication for motor cortex rTMS by a neurologist
• Patient can be followed for the entire duration of the study
• Patient having received informed consent to participate in the study, and having co-signed a consent form with the investigator
• Member or beneficiary of a social security scheme

Exclusion Criteria:

• Industrial accident or litigation
• Contraindication to rTMS or MRI (seismotherapy treatment since the previous month; epilepsy and/or history of epilepsy; history of head trauma; neurosurgical lesion; intracranial hypertension; intracerebral metal clip; piercing; pacemaker; insulin pump; metal prosthesis; pregnant or breast-feeding woman; claustrophobia)
• Drug or psychoactive substance abuse
• Neuropathic pain in the context of a progressive pathology (HIV, cancer, systemic disease disease)
• Presence of other pain more severe than that justifying inclusion
• Patient unable to understand informed consent
• Patient unwilling or unable to stop treatments prohibited during the study
• Patient participating in another research protocol involving a drug within the 30 days prior to inclusion
• Patient deprived of liberty or under legal protection (guardianship, curatorship, safeguard of justice safeguard, family safeguard)
• Minor patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: M1 - DLPFC; Initial primary motor cortex stimulation (M1) followed by cortex prefrontal cortex (DLPFC) : rTMS of M1, washout, rTMS of DLPFC	Device: Repetitive transcranial magnetic stimulation (rTMS) - M1/DLPFC; Repetitive transcranial magnetic stimulation (rTMS) is a treatment technique involving the induction of an electrical current on the surface of the cortex by applying a magnetic field to the scalp. This field is generated using a stimulation loop controlled by a robotic arm linked to a neuronavigation system. rTMS of M1 then rTMS of DLPFC.; Other Names: rTMS
Other: DLPFC - M1; Initial cortex prefrontal cortex (DLPFC) stimulation followed by primary motor cortex stimulation (M1) : rTMS of DLPFC, washout, rTMS of M1	Device: Repetitive transcranial magnetic stimulation (rTMS) - DLPFC/M1; Repetitive transcranial magnetic stimulation (rTMS) is a treatment technique involving the induction of an electrical current on the surface of the cortex by applying a magnetic field to the scalp. This field is generated using a stimulation loop controlled by a robotic arm linked to a neuronavigation system. rTMS of DLPFC then rTMS of M1.; Other Names: rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of pain relief rates between the two stimulation targets (M1 and DLPFC)	Patients are asked how much pain relief they have experienced since the last session.	2 weeks after the last rTMS session for each arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain evolution	Pain evolution via multiple Visual Analogue Scale (components: intensity, unpleasantness, impact on on attention). (Minimum Value : 0 means "no pain" - Maximum value : 10 means "the most intense pain imaginable").	Up to 26 weeks
Evolution of catastrophism	Evolution of catastrophism via the Pain Catastrophizing Scale. People are asked to indicate the degree to which they have the above thoughts and feelings when they are experiencing pain using the 0 (not at all) to 4 (all the time) scale. A total score is yielded (ranging from 0-52), along with three subscale scores assessing rumination, magnification and helplessness.	2 weeks after rTMS sessions
Change in perceived quality of life	Change in perceived quality of life using the EuroQol-5D (EQ5-D). The answers given to ED-5D permit to find 243 unique health states or can be converted into EQ-5D index an utility scores anchored at 0 for death and 1 for perfect health. The EQ-5D questionnaire also includes a Visual Analog Scale (VAS), by which respondents can report their perceived health status with a grade ranging from 0 (the worst possible health status) to 100 (the best possible health status).	2 weeks after rTMS sessions
Adverse events	Potential adverse events reporting during the study	Up to 26 weeks
Progression of depression (Montgomery Asberg Depression Rating Scale - MADRS)	Progression of depression (thymia), assessed by subjective percentage improvement in mood by the MADRS. Montgomery Asberg Depression Rating Scale (MADRS) consists of 10 items to be completed during a clinical interview. Each item has a severity scale from 0 to 6, with higher scores reflecting more severe symptoms. Scores can be added together to give an overall score (from 0 to 60).	2 weeks after rTMS sessions
Progression of depression (Beck Depression Inventory - BDI)	Progression of depression (thymia), assessed by subjective percentage improvement in mood by the Beck Depression Inventory (BDI). It provides a quantitative estimate of depression intensity. Each item consists of 4 sentences corresponding to 4 degrees of increasing intensity on a scale from 0 to 3. The overall score for the depressive syndrome (from 0 to 39) is obtained by adding up the scores for the 13 items.	2 weeks after rTMS sessions
Changes in mean pain intensity	Comparison of changes in mean pain intensity between the two treatment arms by using Visual Analogue Scale (components: intensity, unpleasantness, impact on on attention). (Minimum Value : 0 means "no pain" - Maximum value : 10 means "the most intense pain imaginable").	2 weeks after rTMS sessions
Evolution of affective and sensory components of pain	Evolution of affective and sensory components of pain via the Pain Questionnaire Saint-Antoine (QDSA). This questionnaire contains 58 words divided into 16 categories offering dimensions that to describe the painful experience	2 weeks after rTMS sessions
Neuropathic dimension	Neuropathic dimension: overall score of the Neuropathic Pain Symptoms Inventory (NPSI) questionnaire and its dominant sub-score. The dominant being defined as the score of the dimension (e.g. allodynia, burning, dysesthesia) most painful at the inclusion visit (S0).This questionnaire is used to assess the presence and evolution of neuropathic pain symptoms, as well as the effectiveness of specific neuropathic pain treatments. Based on questioning, it comprises 12 questions (10 descriptive of symptoms and and 2 to assess pain frequency and duration). Score is from 0 ((no pain) to 120 (maximun pain)	Up to 26 weeks

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Neuropathic pain; Depressive Disorder; pain relief; neuromodulation; transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neuromuscular Diseases; Behavioral Symptoms; Peripheral Nervous System Diseases; Mood Disorders; Depression; Depressive Disorder; Neuralgia
• Other Study ID Numbers: 23CH155; ANSM (Other Identifier: 2025-A01697-42)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No