Effect of Electroacupuncture on Sensitive Symptoms of Distal Diabetic Peripheral Neuropathy (EA&DPN)

Effect of Electroacupuncture on Sensitive Symptoms of Distal Diabetic Peripheral Neuropathy and Its Correlation With Nerve Conduction Changes

This is a controlled clinical trial with the aim to study the effects of electroacupuncture on neuropathic pain reduction, quality of life and changes in sensory and motor nerve conduction velocity in patients with type 2 diabetes mellitus, beneficiaries of the familiar medical centers 20, 40 and 41 of the Instituto Mexicano del Seguro Social, at north of Mexico City, in colaboration with the human acupuncture specialty of the Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Mexico.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Peripheral Neuropathic Pain; Diabetic Peripheral Neuropathy; Acupuncture; Diabetic Polyneuropathy; Electroacupuncture; Nerve Conduction
• Intervention / Treatment: Procedure: Electroacupuncture; Procedure: Sham Acupuncture

Detailed Description

Controlled clinical trial to evaluate the effect of electroacupuncture on the reduction of neuropathic pain, quality of life; electrophysiological, inflammatory response, oxidative stress, and genetic expression, in patients with type 2 diabetes mellitus, beneficiaries from the family medical centers 20 , 40 and 41 of the Instituto Mexicano del Seguro Social, at north of Mexico City.

Once the acceptance letter has been signed, a series of questionnaires (MNSI, MDNS, DN-4, NRS, and SF-36), and a physical examination will be carried out to meet the necessary criteria to continue participating.

Only candidates with clinical diagnosis of diabetic polyneuropathy will have an electrophysiological examination by nerve conduction velocity study, if so, patients will be randomized to the electroacupunture or sham acupuncture groups.

Before intervention, laboratory studies will be taken after fasting for 8 to 10 hours, to determine biochemichal profile (glucose, urea, creatinine, uric acid , triglycerides, total cholesterol, HDL and LDL), oxidative stress (Malondialdehyde), inflammatory response (IL-6, IL1β, TNF-α, IL-10 and IL-18 cytokines), and gene expression (5-HT1AR, Neurokinin 1, α-adrenoreceptors, NGF, CX3CR1, GAP-43, and NT3).

Intervention will be applied in a total of 32 acupuncture sessions, divided into two intervention cycles, that is, 16 sessions over two months, with a rest period of one month in between.

At the end of both cycles of interventions, the questionnaires, the nerve conduction velocity study the biochemical and molecular studies will be re-assessed. Finally, this will be re-evaluated after three months post-intervention in order to evaluate the effect of intervention over time.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: José de Jesús Peralta Romero, PhD; Phone Number: 5532318563; Email: drjjperalta@gmail.com
• Study Contact Backup: Name: María Fernanda Pérez Hernández, MD; Phone Number: 5574021093; Email: marferperezh@gmail.com

Study Locations

• Mexico
  • Cuauhtémoc
    • Mexico City, Cuauhtémoc, Mexico, 06720
      • Recruiting
      • Medical research unit in biochemistry, UMAE "Dr. Bernardo Sepúlveda".Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social.
      • Contact: José de Jesús Peralta Romero, PhD; Phone Number: 5532318563; Email: drjjperalta@gmail.com
      • Contact: María Fernanda Pérez Hernández, MD; Phone Number: 5574021093; Email: marferperezh@gmail.com
      • Sub-Investigator: Sergio de Jesús Aguilar Castillo, MD
      • Sub-Investigator: Alejandra Calderón Vallejo, MD
      • Sub-Investigator: Cuauhtémoc Daniel Gómez Jiménez, MsC
      • Sub-Investigator: Eduardo Rodríguez Guerrero, MsC
      • Sub-Investigator: Macedonia Guadalupe Moreno Tovar, MD
      • Sub-Investigator: Fátima Aguilar Morales, MD
      • Sub-Investigator: María Esther Ocharan Hernández, PhD
      • Sub-Investigator: Germán Velázquez García, MsC
      • Sub-Investigator: Citlaltépetl Salinas Lara, PhD
      • Sub-Investigator: Claudia Camelia Calzada Mendoza, PhD
      • Sub-Investigator: Miguel Cruz López, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 58 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with type 2 diabetes.
• Patients with clinical diabetic peripheral polyneuropathy.
• Patients with electrophysiological diagnosis of diabetic peripheral polyneuropathy in its different types of classification.

Exclusion Criteria:

• Type 1 Diabetes or gestational diabetes.
• Systemic autoimmune diseases.
• Hematological disorders.
• HIV diagnosis.
• Cancer in treatment.
• Pregnancy.
• Other types of neurological disorders or neuropathies.
• Intervention with acupuncture six months previously.
• Patients with pacemarkers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham group; Sham acupuncture will be administered in a total of 32 sessions within five months.	Procedure: Sham Acupuncture; Intervention consists of a total of 32 sessions, divided into two intervention cycles, that is, 16 sessions over two months, with a rest period of one month in between. Sham acupuncture will be applied using a nonpuncture device without electrical stimulation at the same acupunctural points as in the EA group.; Other Names: Sham
Experimental: Interventional group; Electroacupuncture will be administered in a total of 32 sessions within five months.	Procedure: Electroacupuncture; Intervention consists of a total of 32 sessions, divided into two intervention cycles, that is, 16 sessions over two months, with a rest period of one month in between. EA is applied for 20 minutes at an alternating frequency of 2 Hz. Acupunctural points are Zusanli (E36), Fenlong (E40), Yinlingquan (B9), Sanyinjiao (B6), Taichong (H3) and Zulinqi (VB41).; Other Names: EA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nerve Conduction Velocity	Measured by Nerve Conduction Velocity Study using the VIKING LIFE-SAVING EQUIPMENT, to determine Motor and Sensitive Nerve Conduction Velocity of common peroneal nerve, sural nerve, and tibial nerve. Sensitive Nerve Conduction (SCV). Distance between the receiving point and the stimulus point. SCV normal values: Peroneal nerve ≥ 41 m/s, tibial nerve ≥ 44 m/s, sural nerve ≥ 50 m/s. Motor Conduction Velocity (MCV). Distance between two points and the difference in incubation between them after superstimulation of the corresponding nerve branch. MCV normal values: Peroneal nerve ≥ 41 m/s, tibial nerve ≥ 44 m/s, sural nerve ≥ 60 m/s. *Values below those stipulated above indicate that NCV has slowed down, and is abnomal. The investigators expect a diminishment of SCV and MCV in sham acupuncture group from the first cycle of intervention whereas electroacupuncture group remains unchanged or even increases SCV and MCV.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxidative Stress	Determined by quantifying the concentrations of the lipoperoxidation product Malondialdehyde (MDA). An increase of MDA is expected in the sham group, while in the electroacupuncture group it is expected to decrease.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Michigan Neuropathy Screening Instrument (MNSI).	It will be assessed with a lower extremity examination by a health professional of both feet in search of deformities, dry skin, calluses, infections, fissures and ulcers. Complemented with measurement of vibratory sensation, ankle reflexes, and Semmes-Weinstein monofilament test. The investigators expect improvement in the physical aspect of the foot in the electroacupuncture group, while in the sham acupuncture group the complication progresses.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Michigan Diabetic Neuropathy Score (MDNS)	Composed of three items where the sensory compromise is evaluated with the perception of vibration, 10 gr. monofilament and pin prick, in addition to the muscular strength of the toes, and the bicipital, tricipital, quadriceps and achilles muscle reflexes. The investigators expect a diminishment of MDNS score and clinical improvement in the electroacupuncture group and progression of clinical manifestations in the sham group.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Douleur Neuropathique en 4 Questions (DN-4)	A screening tool for neuropathic pain consisting of 10 interview questions (DN4-interview) and physical tests. A score greater than 4 points suggests neuropathic pain. The investigators expect decreased scores in the electroacupuncture group and increased or persistent scores in the sham group.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Numerical Pain Rating Scale (NRS)	Patients are only asked to circle the number between 0 and 10, 0 and 20 or 0 and 100 that best matches the intensity of their pain currently and in the last 7 days, where zero usually represents "no pain", while the upper limit represents "the worst pain of their life". The investigators expect diminishment of rating scale in electroacupuncture group and an increase in sham acupuncture group.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Quality life (SF-36)	It will be measured by The Short Form-36 Health Survey (SF-36) a measure of health status that consists of eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health), which are the weighted sums of the questions in their section. The investigators expect quality life improvement in electroacupuncture group while in sham acupuncture group might worsen.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Inflammatory response	Assessed by changes in serum concentrations of proinflammatory (IL-6, IL1β, TNF-α and IL-18) and anti-inflammatory (IL-10) cytokines determined by quantitative ELISA by flow cytometry. The investigators expect increase of anti-inflammatory cytokine and decrease of proinflammatory cytokines in the electroacupuncture group, while in the sham group this is inversely presented.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.
Genetic expression	mRNA expression of 5-HT1AR, Neurokinin 1, α-adrenoreceptors, NGF (Nerve growth factor), CX3CR1, GAP-43 (Growth associated protein 43) and Neurotrophin (NT3), (Chemoline receptor 1) genes quantified by real-time PCR. The investigators expect an increase in gene expression in patients with electroacupuncture while in sham patients it is decreased or even unchanged.	Baseline evaluation, after the first and second cycle of intervention, respectively, and three months after the end of the intervention.

Collaborators and Investigators

• Sponsor: Instituto Mexicano del Seguro Social
• Collaborators: Instituto Nacional de Salud Publica, Mexico; Universidad Nacional Autonoma de Mexico; National Polytechnic Institute, Mexico; Facultad de Medicina, UNAM; Escuela Superior de Medicina, Instituto Politécnico Nacional; Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional; Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Mexico; Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de Mexico
• Investigators: Principal Investigator: José de Jesús Peralta Romero, PhD, Instituto Mexicano del Seguro Social

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Acupuncture; Electroacupuncture; Diabetic Polyneuropathy; Diabetic Peripheral Neuropathic Pain; Nerve Conduction; Diabetic Peripheral Neuropathy; Diabetic Pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Neuralgia; Peripheral Nervous System Diseases; Polyneuropathies; Diabetic Neuropathies
• Other Study ID Numbers: R-2020-785-070; 09-CEI-009-20160601 (Other Identifier: CONBIOÉTICA); 17 CI 09 015 006 (Other Identifier: COFEPRIS)

Plan for Individual participant data (IPD)

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

Study Data/Documents

1. Protocol reapproval report

Drug and device information, study documents

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