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

Chongqing Medical University

Status: Enrolling

Conditions: Painful Diabetic Neuropathy

Treatments: Device: Sham Low-Intensity Focused Ultrasound; Device: Low-Intensity Focused Ultrasound (LIFU)

Study type: Interventional

Funder types: Other

Identifiers

NCT05624762

DPN-China2022

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

LIFU group

Active Comparator group

Description:

receive LIFU therapy

Treatment:

Device: Low-Intensity Focused Ultrasound (LIFU)

Control group

Sham Comparator group

Description:

receive sham LIFU therapy

Treatment:

Device: Sham Low-Intensity Focused Ultrasound