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

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.

Study Overview

• Status: Recruiting
• Conditions: Painful Diabetic Neuropathy
• Intervention / Treatment: Device: Low-Intensity Focused Ultrasound (LIFU); Device: Sham Low-Intensity Focused Ultrasound

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qian Ge, Professor; Phone Number: +8619946802662; Email: geqian@hospital.cqmu.edu.cn

Study Locations

• China
  • Chongqing, China, 400016
    • Recruiting
    • The First Affiliated Hospital of Chongqing Medical University
    • Contact: Qian Ge, Professor; Phone Number: +8619946802662; Email: geqian@hospital.cqmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The motor nerve conduction velocity (MNCS)	The motor nerve conduction velocity (MNCS) measured in peroneal, tibial, and sural nerves using electromyography	7 days
The sensory nerve conduction velocity (SNCS)	The sensory nerve conduction velocity (SNCS) were measured in peroneal, tibial, and sural nerves using electromyography	7 days

Collaborators and Investigators

• Sponsor: Chongqing Medical University
• Investigators: Study Director: Qian Ge, Professor, Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Painful Diabetic Neuropathy; low-intensity focused ultrasound
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; Diabetic Neuropathies
• Other Study ID Numbers: DPN-China2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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