Noninvasive Cortical Neurostimulation For Diabetic Neuropathic Pain

November 29, 2023 updated by: Jens Brøndum Frøkjær

Treatment of Pain and Sensory Dysfunction in Diabetic Neuropathy by Brain Neuromodulation

To investigate whether transcranial direct current stimulation can alleviate pain and sensory related disturbances in individuals with type 1 diabetes and peripheral neuropathy through neuromodulation of the CNS as compared to sham treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study is a randomized, cross-over, controlled investigation. The overall objective of this study is to assess the pain-relieving effect of four weeks' transcranial direct current stimulation (tDCS) in individuals with type 1 diabetes and painful polyneuropathy not responding adequately to traditional pharmacological pain treatment, in comparison to the effect of four weeks' sham treatment. Both treatments will be performed using a commercially available and validated device called Sooma tDCS. Sooma tDCS device is a non-invasive neurostimulator that has been CE-marked for the treatment of depression, chronic pain including neuropathic pain and fibromyalgia. The study will begin with a 2-week baseline registration period, in which the patients will receive no treatment. Next, the baseline period will be followed by a 4-week treatment period where the subjects will be randomized to either active treatment or sham treatment. Afterwards, a wash-out period of 6 weeks will occur. Finally, in the second treatment period the patients will switch in treatment assignment, meaning that patient who received active treatment will now receive sham treatment and vice versa. During both treatments, the patients will be asked to self-administer one stimulation dose daily, five times a week. During the whole study, subjects will be asked to complete a pain diary and several questionnaires. Moreover, at the beginning and end of each treatment period (four times), all subjects will undergo testing which will include brain magnetic resonance imaging (MRI) and quantitative sensory testing (QST). The primary efficacy parameters to be evaluated are short and longer lasting alleviation of clinical chronic pain and quality of life.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jens Brøndum Frøkjær, MD, Ph.D
  • Phone Number: +45 9766 5105
  • Email: jebf@rn.dk

Study Contact Backup

  • Name: Janusiya Anajan Muthulingam, M.Sc., Ph.D
  • Phone Number: +45 9766 5119
  • Email: j.muthulingam@rn.dk

Study Locations

  • Denmark
      • Aalborg, Denmark, 9000
        • Recruiting
        • Aalborg University Hospital
        • Contact:
          • Jens Brøndum Frøkjær, MD, PhD
          • Phone Number: 97 66 51 05
          • Email: jebf@rn.dk
        • Contact:
          • Janusiya Anajan, M.Sc, PhD
          • Phone Number: 97 66 51 19
          • Email: jebf@rn.dk
        • Sub-Investigator:
          • Niels Ejskær, MD, PhD
        • Sub-Investigator:
          • Asbjørn Mohr Drewes, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Minimum age of 18 years.
  • Type-1 diabetes
  • Clinically established peripheral neuropathy
  • DN4 of ≥4 points indicating that the patient is suffering from neuropathic pain.
  • NRS pain scores >3
  • Acceptable screening blood samples according to medical judgement
  • Signed informed consent

Exclusion Criteria:

  • Contraindications to MRI
  • Not being able to understand Danish (written and/or verbally)
  • Not being able to comply with the study procedures including home-treatment e.g., due to senile dementia, etc.
  • Previous brain surgery
  • Present alcohol or drug abuse
  • Major mental and psychiatric disorders
  • Pregnancy
  • Active cancer-disease
  • Known neural damage or disease in the neural system (e.g., MS or Guillain-Barre) other than diabetic neuropathy
  • Previous chemotherapy or intake of experimental medicine
  • Active herpes simplex virus or varicella zoster virus infection or known HIV
  • Other reasons for limb pain (e.g., critical limb ischemia and lower back pain with radiating pain etc.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active tDCs
Active tDCS will be administered through a pair of conductive rubber electrodes covered by saline soaked sponges (35 cm2). The current will be delivered continuously at 2 mA for 30 min through a battery-driven constant-current stimulator. An anodal electrode is placed above the primary motor cortex, M1, while a cathode is placed above the contralateral supraorbital area.
Device: Sooma Oy (tDCS), Helsinki, Finland
Using the 2-channel neuro-stimulator Sooma tDCS equipment we provide 20 minutes of 2 mA anodal stimulation of the primary motor cortex (M1)
Sham Comparator: Sham tDCS
Sham stimulation will be delivered to the motor cortex using a sham tDCS device that delivers a direct current for 30 seconds at the beginning and end of tDCS to provide sensory experiences similar to active stimulation.
Device: Sooma Oy (Sham), Helsinki, Finland
For the sham treatment, an electrical current will also be increased from 0 mA to 2 mA over the first 30 seconds, however, the current will be ramped back down to 0 mA after the initial ramp-up phase and no stimulation is delivered for the rest of the treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in numeric rating scale (NRS) scores in pain diary
Time Frame: 20 weeks

The primary clinical efficacy parameter to be evaluated is pain relief. In the clinical part of the study the efficacy is assessed as changes in the daily experience of pain, which will be measured using a patient pain diary based on the NRS. Maximum intensity and average daily NRS will be recorded on daily basis.

Minimum: 0 Maximum: 10
20 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brief Pain Inventory questionnaire (mBPI)
Time Frame: Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Neuropathy Total Symptom Score-6 (NTSS-6)
Time Frame: Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
A score >0 indicates the presence of >1 sensory symptom. Clinically significant symptoms are defined as an NTSS-6 total score >6 points.
Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Hospital Anxiety and Depression Scale (HADS)
Time Frame: Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
HADS is a fourteen-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression.
Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Brain MRI
Time Frame: Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Resting state functional MRI will be employed to detect brain activity and functional connectivity changes based on BOLD signals before and after treatment of each patient.
Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Quantitative sensory testing
Time Frame: Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
QST includes temporal summation, pressure pain thresholds, and conditioned pain modulation (CPM).
Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jens Brøndum Frøkjær

Collaborators

Novo Nordisk A/S
Vissing fonden

Investigators

  • Principal Investigator: Jens Brøndum Frøkjær, MD, Ph.D, Professor and Chief Physician at Aalborg University Hospital, Department of Radiology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

August 28, 2023

First Submitted That Met QC Criteria

November 29, 2023

First Posted (Estimated)

December 1, 2023

Study Record Updates

Last Update Posted (Estimated)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NOPAIN study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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