Clinical trial NCT06247423: High-frequency Alternating Current Stimulation for Tremor in Parkinson's Disease.
Official title: Effects of 10kHz High-frequency Alternating Current Transcutaneous Stimulation on Tremor in People with Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease and Parkinsonism
Nerve Block
Motor Activity
Keywords: High-frequency alternating current stimulation
Parkinson's Disease
Tremor
Motor activity
Lead sponsor: University of Castilla-La Mancha
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Innovation, Spain
name: Asociación Parkinson Toledo (CAP Toledo)
First posted: 2024-02-07
Enrollment: 16
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two interventions will be performed:

* Intervention A: active stimulation (High-frequency current stimulation 10kHz).
* Intervention B: sham stimulation (simulated electrical stimulation).
Primary purpose: TREATMENT

Brief summary: The goal of this randomized, double-blind, placebo-controlled, crossover study is to test the effectiveness of 10 kilohertz (kHz) high-frequency transcutaneous stimulation for tremor in people with Parkinson's disease. The main questions it aims to answer are:

* Compare the effectiveness between sham stimulation and real stimulation (10kHz) for different types of tremors \[rest tremor, postural tremor, kinetic tremor\], fine motor skills, and maximal isometric handgrip strength.
* Register adverse events, the blinding success of participants and evaluator, and subjective perception of tremor improvement.

Participants will perform the following tasks in an "off" state (without levodopa and dopamine agonists medication). All of them were performed on the upper limb with more tremor.

* Rest Tremor: Forearm on the armrest, count backward from 100 to 0 as fast as possible for 1 minute and 30 seconds.
* Postural Tremor: Extend the arm parallel to the floor (90º shoulder flexion with the forearm extended) for 30 seconds.
* Kinetic Tremor: Hold a cup by the handle, raise it close to the mouth for 3 seconds, then return to the initial position.
* Fine Motor Skills: Complete the nine-hole peg test, placing pegs into holes as quickly as possible.
* Handgrip Strength: Squeeze the device as strongly as possible for 3 seconds, then rest for 15 seconds.

Detailed description: High-frequency alternating current (HFAC) stimulation involves applying electrical stimulation with a frequency above 1 kilohertz (kHz) to peripheral nerves, inducing immediate, reversible nerve block without causing damage. Studies have shown that frequencies between 10 and 20 kHz reduce maximal isometric grip strength when applied transcutaneously over peripheral nerves, suggesting a partial block of A-alpha fibers, which may help reduce nerve hyperexcitability and motor activity. Tremor-related pathologies, influenced by abnormal muscle activity, significantly impact the quality of life of patients, particularly those with Parkinson's disease (PD), where tremor represents one of the most annoying and disabling symptoms since early stages of the disease.

For these reasons, tremor-related pathologies could benefit from HFAC stimulation. To our knowledge, no studies have applied HFAC stimulation in patients with PD. The main objective of this study is to compare the effectiveness of sham stimulation and real stimulation (10kHz) for tremor \[rest tremor, postural tremor, kinetic tremor\] in people with PD. Secondary objectives include analyzing the effectiveness of stimulation for fine motor skills and maximal isometric grip strength in people with PD, as well as documenting adverse events and evaluating blinding success.

A double-blind, randomized, crossover-design study will be conducted at the University of Castilla-La Mancha. Two interventions will be performed in people with Parkinson's Disease during "Off" state, randomizing the order: Intervention A: 10kHz stimulation; Intervention B: sham electrical stimulation.

Eligibility criteria: Inclusion Criteria:

* Patients must have a confirmed diagnosis of Parkinson's Disease (PD) by a neurologist or specialist physician, specifically with tremor as defined by the consensual declaration of the "Movement Disorder Society".
* Must possess adequate cognitive capacity to perform the tests and understand all the procedure.
* Tolerance to the application of electrotherapy.

Exclusion Criteria:

* Treatment for tremor suppression (deep brain stimulation or medication within 5 hours).
* Altered sensitivity in the intervention area
* Recent traumatism or surgeries which interfere with the measures
* Presence of pacemakers or other implanted electrical devices
* Tattoos or other external agents in the treatment area
* Comorbidities or conditions affecting tremor or coordination (cerebellar injury)

Primary outcomes:
measure: Resting tremor
timeFrame: Before stimulation (T0), during stimulation [at 10 minutes] (T1), immediately after the end of the stimulation [at 20 minutes] (T2), and 10 minutes after the end of the stimulation [at 30 minutes] (T3).
measure: Postural tremor
timeFrame: Before stimulation (T0), during stimulation [at 10 minutes] (T1), immediately after the end of the stimulation [at 20 minutes] (T2), and 10 minutes after the end of the stimulation [at 30 minutes] (T3).
measure: Kinetic tremor
timeFrame: Before stimulation (T0), during stimulation [at 10 minutes] (T1), immediately after the end of the stimulation [at 20 minutes] (T2), and 10 minutes after the end of the stimulation [at 30 minutes] (T3).
Secondary outcomes:
measure: Fine motor skills-finger dexterity
timeFrame: Before stimulation (T0), during stimulation [at 10 minutes] (T1), immediately after the end of the stimulation [at 20 minutes] (T2), and 10 minutes after the end of the stimulation [at 30 minutes] (T3).
measure: Maximal isometric grip strength
timeFrame: Before stimulation (T0), during stimulation [at 10 minutes] (T1), immediately after the end of the stimulation [at 20 minutes] (T2), and 10 minutes after the end of the stimulation [at 30 minutes] (T3).
measure: Blinding success
timeFrame: 10 minutes after the end of the stimulation [at 30 minutes] (T3).
measure: Adverse events
timeFrame: 10 minutes after the end of the stimulation [at 30 minutes] (T3) and 24 hours after the stimulation (T4).
measure: Subjective degree of improvement
timeFrame: 10 minutes after the end of the stimulation [at 30 minutes] (T3).
Other outcomes:
Locations:
city: Toledo
country: Spain
facility: Universidad de Castilla La Mancha
Study officials:
affiliation: Toledo Physiotherapy Research Group (GIFTO). Castilla la Mancha University.
name: Julio Gómez-Soriano, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arruda BS, Reis C, Sermon JJ, Pogosyan A, Brown P, Cagnan H. Identifying and modulating distinct tremor states through peripheral nerve stimulation in Parkinsonian rest tremor. J Neuroeng Rehabil. 2021 Dec 25;18(1):179. doi: 10.1186/s12984-021-00973-6.
citation: Jitkritsadakul O, Thanawattano C, Anan C, Bhidayasiri R. Tremor's glove-an innovative electrical muscle stimulation therapy for intractable tremor in Parkinson's disease: A randomized sham-controlled trial. J Neurol Sci. 2017 Oct 15;381:331-340. doi: 10.1016/j.jns.2017.08.3246. Epub 2017 Aug 24.
citation: Contreras VT, Araque W, Delgado VS. Trypanosoma cruzi: metacyclogenesis in vitro--I. Changes in the properties of metacyclic trypomastigotes maintained in the laboratory by different methods. Mem Inst Oswaldo Cruz. 1994 Apr-Jun;89(2):253-9. doi: 10.1590/s0074-02761994000200026.