The Therapeutic Effect of Low-intensity Focused Ultrasound on Painful Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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Diabetic painful peripheral neuropathy (DPN) constitutes a serious threat to the outcomes of patients with diabetes. Yet, the treatments for targeting the underlying nerve damage and relieving pain are limited. The low-intensity focused ultrasound (LIFU) has been demonstrated to regulate neuronal activity without any concomitant tissue damage. Studies in animal models have shown that LIFU could protect nerve cells against inflammation and oxidative stress, as well as stimulate neurotrophic factor production. In humans, LIFU has been reported to be effective in relieving peripheral neurogenic pain caused by carpal tunnel syndrome and chemotherapy drugs. Thus, we aim to design a randomized controlled double-blind study by using LIFU. The primary endpoint is the patient's pain score (NRS), and the secondary endpoints include Neuropathy Symptom Score (NSS) and Neuropathy Deficit Score (NDS). Through this study, we anticipate establishing a new method for managing painful DPN.

Detailed Description
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Diabetic peripheral neuropathy (DPN) is a major cause of disability and mortality due to pain, loss of protective sensation, foot ulceration, amputation, and risk of falls, therefore constituting a serious threat to the outcomes of patients with diabetes and their treatment costs. The pathogenesis of DPN has been proposed as an inflammatory and oxidative stress injury in nerve cells caused by glucose and lipid metabolism disorder. Yet, the treatments for targeting the underlying nerve damage and relieving pain are limited. The widely used drugs such as Mecobalamine and Lipoic acid are not effective in some patients (about 2/3). Others, like anticonvulsant (e.g. Dabapentin), antidepressant (e.g. Duloxetine), and central opioid analgesics (e.g. Tramadol), are effective in the short-term, but they may lead to side effects for long-term use such as impairment of cognitive function, insomnia, and addiction, etc. The low-intensity focused ultrasound (LIFU) is regarded as the magnitude of ultrasonic intensity similar to or below that typically used in diagnostic ultrasound examinations. Although currently LIFU has not been applied in DPN, a number of studies have demonstrated that it can regulate neuronal activity without any concomitant tissue damage. Studies in animal models have shown that LIFU could protect nerve cells against inflammation and oxidative stress, as well as stimulate neurotrophic factor production. In humans, LIFU has been reported to be effective in relieving pain caused by carpal tunnel syndrome (Median nerve compression). Also, several studies have evidenced that cancer patients suffering from chemotherapy drug-induced peripheral neurogenic pain had significant improvement by LIFU treatment. Thus, we aim to take advantage of LIFU to treat the painful DPN. We plan to design a randomized controlled double-blind study. The primary endpoint is the patient's pain score (NRS), and the secondary endpoints include Neuropathy Symptom Score (NSS) and Neuropathy Deficit Score (NDS). Through this study, we anticipate establishing a new method for managing painful DPN.

Official Title
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The Therapeutic Effect of Low-intensity Focused Ultrasound on Painful Diabetic Peripheral Neuropathy

Conditions
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Painful Diabetic Neuropathy

Intervention / Treatment
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* Device: Low-Intensity Focused Ultrasound (LIFU)
* Device: Sham Low-Intensity Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 20 and 80 years having diabetes based on the criteria of the World Health Organization (WHO 1999) Having diabetic painful neuropathy for more than 1 month but less than 5 years no alcohol addiction (consumption<140g/week in men and <70g/week in women) no history of cerebral infarction/hemorrhage or other known nervous system disease no active infections in the skin Exclusion Criteria: having abnormalities in levels of Vitamin B12, Hemoglobin, and TSH. HbA1C>10% having moderate or severe hepatic and renal dysfunctions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LIFU group<br>receive LIFU therapy | Device: Low-Intensity Focused Ultrasound (LIFU)<br>* LIFU device (LCA200; Chongqing Haifu Medical Technology Co., Ltd., Chongqing, China).<br>|
| Sham Comparator: Control group<br>receive sham LIFU therapy | Device: Sham Low-Intensity Focused Ultrasound<br>* Sham Low-Intensity Focused Ultrasound<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain score | the pain score is evaluated using a numeric pain rating (0-10) scale (NRS) | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathy Symptom Score (NSS) | the NSS is determined using a questionnaire | 7 days | 
| Neuropathy Deficit Score (NDS) | the NDS is examined by an experienced neurologist | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Painful Diabetic Neuropathy, low-intensity focused ultrasound