Efficacy of Repetitive Trans-spinal Magnetic Stimulation on Axial Motor Symptoms in PD

NCT ID: NCT05271513

Last Updated: 2024-01-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2023-07-01

Brief Summary

The purpose of this randomized trial was to evaluate the efficacy of repeated sessions of trans-spinal magnetic stimulation on gait abnormality, and posture abnormalities in patients with idiopathic Parkinson's disease.

Detailed Description

Parkinson's disease is the second most common age-related neurodegenerative disease after Alzheimer's disease[1], patients with advanced Parkinson's disease (PD) often present with axial symptoms, including abnormal posture, postural instability, and gait disorder [2]. These axial symptoms are the main factors that reduce the activities of daily living (ADL) and quality of life (QOL) of PD patients. Gait disorders are among the most prevalent problems in the advanced phase of Parkinson's disease (PD) and are relatively resistant to dopaminergic treatment. Freezing of gait (FoG) affects 7% of patients in early PD and reaches 60% in advanced stages [3]. Patients with PD also suffer from pain significantly more frequently than normal subjects. Low back pain and leg pain are the most commonly experienced pain symptoms in PD patients. One of the reasons is considered to be the decreased threshold of pain due to abnormality of the dopaminergic system in the basal ganglia of PD patients [3.4]. Administration of anti-parkinsonian medication or Deep brain stimulation results in increased pain thresholds. Treatment by medication or DBS is often ineffective for low back pain caused by postural deformity and is also ineffective for radicular or peripheral neuropathic. Because pain is an important factor that reduces the ADL and QOL of patients, the establishment of new and effective therapy is essential [5.6]. A positive effect of epidural spinal cord stimulation (SCS) on locomotive activity has been reported in animal models and small cohorts of PD patients and seems to be promising.[7] Transcutaneous SCS is an emerging method that activates similar target neural structures noninvasively and has recently been explored for the treatment of spasticity after spinal cord injury.[8] Here, the investigators will assess the safety and efficacy of transcutaneous magnetic SCS on freezing of gait (FoG) and other motor symptoms in a cohort of PD patients.

The investigators will be going to carry out a double-blinded randomized, case-controlled study on 42 patients who will be randomly chosen and categorize them into 2 groups, 21 patients each. The 1st group will receive real transcranial magnetic stimulation applied over each hand area High frequency 20 HZ, 80% of the motor threshold of hand, 10 sec for each train, 20 train with a total of 2000 pulses for each side plus transcutaneous spinal cord stimulation (over mid-dorsal vertebrae (thoracic 6) high frequency 10 HZ, 80% of the motor threshold of leg area10 sec for each train, 10 trains with total 1000 pulses for 10 consecutive days. The second group will receive the same protocol but the spinal stimulation will be sham stimulation as the coil lie perpendicular to the vertebral axis. Then the investigators will be going to compare the results of two groups at the end of sessions, one and two months after the last session to find out the efficacy of repetitive transcutaneous magnetic stimulation of the spinal cord on gait abnormalities and posture abnormalities, relief of pain, UPDRS, and as well as the quality of life in patients with idiopathic Parkinson's disease

Conditions

Adverse Effect of Drug Therapy Levodopa

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

real transcranial magnetic stimulation plus real transcutaneous magnetic stimulation of spinalcord

the patient will receive real rTMS 2000 pulses for each hand area 20Hz 80% of Motor threshold of the hand, 10 trains, each train 10 seconds over the hand area plus 1000 pulses 10 Hz 80% of the motor threshold of the leg 10 trains, and each train 10 seconds over the mid-cervical vertebrae for consecuative 10 days (5 days/week)

Group Type: ACTIVE_COMPARATOR

non invasive repetitive magnetic stimulation (real Transcranial + real trans-spinal )

Intervention Type: DEVICE

repetitive transcranial magnetic stimulation and trans-spinal magnetic stimulation

real transcranial magnetic stimulation with sham transcutaneous magnetic stimulation of spinalcord

the patient will receive real rTMS 2000 pulses for each hand area 20Hz 80% of Motor threshold of the hand, 10 trains, each train 10 seconds plus sham stimulation 1000 pulses 10 Hz 80% of the motor threshold of the leg 10 trains, and each train 10 seconds over the mid-dorsal vertebrae for 10 consecutive days (5 sessions/week)

Group Type: ACTIVE_COMPARATOR

non invasive repetitive magnetic stimulation (real Transcranial + sham trans-spinal )sham trans-spinal magnetic stimulation

Intervention Type: DEVICE

sham trans-spinal magnetic stimulation

Interventions

non invasive repetitive magnetic stimulation (real Transcranial + real trans-spinal )

repetitive transcranial magnetic stimulation and trans-spinal magnetic stimulation

Intervention Type: DEVICE

non invasive repetitive magnetic stimulation (real Transcranial + sham trans-spinal )sham trans-spinal magnetic stimulation

sham trans-spinal magnetic stimulation

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Men or women of at least 40-80 years of age.

2. Are reliable and willing to make themselves available for the duration of the study and are willing to follow up.

3. Medically stable outpatients with a confirmed diagnosis of idiopathic PD according to United Kingdom Brain Bank Criteria

4. Clear written informed consent from each participant in the trial.

5. Patients after at least 6 h free of parkinsonian drugs (off-state).

Exclusion Criteria

1. Pregnants, breastfeeding, or willing to be pregnant during the study.

2. Presence of a clinically significant medical or psychiatric condition that may increase the risk associated with the study

3. Participation in any other type of medical research that may interfere with the interpretation of the study.

4. Patients with severe motor disability (bed-ridden ) that may interfere with the study procedure.

5. History of surgical or invasive intervention for Parkinson's disease.

6. Patients with a history of seizures or epilepsy including history in a first-degree relative or patients on treatment that reduce the seizure threshold.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Eman M. Khedr

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Assiut University

Asyut, , Egypt

Countries

Egypt

References

Fuentes R, Petersson P, Nicolelis MA. Restoration of locomotive function in Parkinson's disease by spinal cord stimulation: mechanistic approach. Eur J Neurosci. 2010 Oct;32(7):1100-8. doi: 10.1111/j.1460-9568.2010.07417.x.

Reference Type: BACKGROUND

PMID: 21039949 (View on PubMed)

Doherty KM, van de Warrenburg BP, Peralta MC, Silveira-Moriyama L, Azulay JP, Gershanik OS, Bloem BR. Postural deformities in Parkinson's disease. Lancet Neurol. 2011 Jun;10(6):538-49. doi: 10.1016/S1474-4422(11)70067-9. Epub 2011 Apr 22.

Reference Type: BACKGROUND

PMID: 21514890 (View on PubMed)

Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA. Spinal cord stimulation restores locomotion in animal models of Parkinson's disease. Science. 2009 Mar 20;323(5921):1578-82. doi: 10.1126/science.1164901.

Reference Type: BACKGROUND

PMID: 19299613 (View on PubMed)

Moorehead MK, Ardelt-Gattinger E, Lechner H, Oria HE. The validation of the Moorehead-Ardelt Quality of Life Questionnaire II. Obes Surg. 2003 Oct;13(5):684-92. doi: 10.1381/096089203322509237.

Reference Type: BACKGROUND

PMID: 14627461 (View on PubMed)

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE. Parkinson disease. Nat Rev Dis Primers. 2017 Mar 23;3:17013. doi: 10.1038/nrdp.2017.13.

Reference Type: RESULT

PMID: 28332488 (View on PubMed)

Agari T, Date I. Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson's disease. Neurol Med Chir (Tokyo). 2012;52(7):470-4. doi: 10.2176/nmc.52.470.

Reference Type: RESULT

PMID: 22850494 (View on PubMed)

Defazio G, Berardelli A, Fabbrini G, Martino D, Fincati E, Fiaschi A, Moretto G, Abbruzzese G, Marchese R, Bonuccelli U, Del Dotto P, Barone P, De Vivo E, Albanese A, Antonini A, Canesi M, Lopiano L, Zibetti M, Nappi G, Martignoni E, Lamberti P, Tinazzi M. Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study. Arch Neurol. 2008 Sep;65(9):1191-4. doi: 10.1001/archneurol.2008.2.

Reference Type: RESULT

PMID: 18779422 (View on PubMed)

Djaldetti R, Shifrin A, Rogowski Z, Sprecher E, Melamed E, Yarnitsky D. Quantitative measurement of pain sensation in patients with Parkinson disease. Neurology. 2004 Jun 22;62(12):2171-5. doi: 10.1212/01.wnl.0000130455.38550.9d.

Reference Type: RESULT

PMID: 15210877 (View on PubMed)

Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, Montastruc JL, Rascol O. Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord. 2005 Dec;20(12):1557-63. doi: 10.1002/mds.20629.

Reference Type: RESULT

PMID: 16078219 (View on PubMed)

Gerdelat-Mas A, Simonetta-Moreau M, Thalamas C, Ory-Magne F, Slaoui T, Rascol O, Brefel-Courbon C. Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study. J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1140-2. doi: 10.1136/jnnp.2007.120212. Epub 2007 May 15.

Reference Type: RESULT

PMID: 17504881 (View on PubMed)

Yadav AP, Nicolelis MAL. Electrical stimulation of the dorsal columns of the spinal cord for Parkinson's disease. Mov Disord. 2017 Jun;32(6):820-832. doi: 10.1002/mds.27033. Epub 2017 May 12.

Reference Type: RESULT

PMID: 28497877 (View on PubMed)

Hofstoetter US, Freundl B, Danner SM, Krenn MJ, Mayr W, Binder H, Minassian K. Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury. J Neurotrauma. 2020 Feb 1;37(3):481-493. doi: 10.1089/neu.2019.6588. Epub 2019 Aug 9.

Reference Type: RESULT

PMID: 31333064 (View on PubMed)

Postuma RB, Poewe W, Litvan I, Lewis S, Lang AE, Halliday G, Goetz CG, Chan P, Slow E, Seppi K, Schaffer E, Rios-Romenets S, Mi T, Maetzler C, Li Y, Heim B, Bledsoe IO, Berg D. Validation of the MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2018 Oct;33(10):1601-1608. doi: 10.1002/mds.27362. Epub 2018 Aug 25.

Reference Type: RESULT

PMID: 30145797 (View on PubMed)

Khedr EM, Haridy NA, Korayem MA, Tawfik AM, Hamed AA. In PD, Non-Invasive Trans-Spinal Magnetic Stimulation Enhances the Effect of Transcranial Magnetic Stimulation on Axial Motor Symptoms: A Double-Blind Randomized Clinical Trial. Neurorehabil Neural Repair. 2025 Feb;39(2):126-137. doi: 10.1177/15459683241300547. Epub 2024 Dec 11.

Reference Type: DERIVED

PMID: 39659276 (View on PubMed)

Other Identifiers

rTSMS in Parkinson's disease

Identifier Type: -

Identifier Source: org_study_id