Noninvasive Cortical Neurostimulation For Diabetic Neuropathic Pain

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06152887
• Other study ID #: NOPAIN study
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Aalborg University Hospital
• Contact: Jens Brøndum Frøkjær, MD, Ph.D
• Phone: 9766 5105
• Email: jebf[@]rn.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Diabetic Neuropathies
• Diabetic Neuropathy, Painful

Intervention

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)
• 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.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg

Sponsors (3)

Lead Sponsor	Collaborator
Jens Brøndum Frøkjær	Novo Nordisk A/S, Vissing fonden

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in numeric rating scale (NRS) scores in pain diary	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	Brief Pain Inventory questionnaire (mBPI)		Baseline, week 4 (treatment I), week 10, week 14 (treatment II), week 18 (follow-up).
Secondary	Neuropathy Total Symptom Score-6 (NTSS-6)	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).
Secondary	Hospital Anxiety and Depression Scale (HADS)	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).
Secondary	Brain MRI	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).
Secondary	Quantitative sensory testing	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).