The Effect of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment in Parkinson's Disease (PD)

The Effect of High Frequency Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment in Parkinson's Disease

This study aims to assess the therapeutic role of rTMS on parkinson's patients with cognitive impairment. Patients diagnosed with Parkinson's Disease and cognitive impairment will be recruited. All patients will be admitted and will be allocated randomly into two groups one of which will receive real sessions of high frequency rTMS for each hemisphere for 10 consecutive sessions totally over period of 10 days with repeated booster sessions every month during the period of follow up. The other will receive sham sessions.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease With Cognitive Impairment
• Intervention / Treatment: Device: repetitive Transcranial Magnetic Stimulation

Detailed Description

This study aims to assess the therapeutic role of rTMS on parkinson's patients with cognitive impairment. Thirty PD patients with cognitive impairment using United Kingdom (UK ) bank criteria for PD will be recruited from outpatient clinic in Assiut University. All patients will be admitted at Neuropsychiatric Department, Assiut University Hospital/ Assiut, Egypt.Each patient fulfilled the inclusion criteria as having score less than 24 on Mini-Mental Status Examination will be recruited. The patients will be allocated randomly into two groups one of which will receive real sessions of high frequency rTMS (25 HZ), with intensity of 80% of resting motor threshold detected from the hand motor area, with total 2000 pulses for each hemisphere for 10 consecutive sessions totally over period of 10 days with repeated booster session every month during the period of follow up among three months. The other will receive sham sessions. All subjects will be followed up by selected clinical rating scales at different intervals pre session, post 10 sessions, and after one, two and three months.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 11517
    • Assiut University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients with Parkinson's Disease who were diagnosed according to UK bank criteria for PD, Aged 45-75 years, with criteria for cognitive impairment (Mini-Mental Status Examination< 24), and consent obtained from the patient or his caregiver.

Exclusion Criteria:

• History of repeated head injury
• History of repeated cerebrovascular strokes
• History of defined encephalitis
• Oculogyric crisis, supranuclear gaze palsy
• Family history of more than one relative
• History of drug intake as antipsychotics or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure
• Moderate and Severe depression (Hamilton Depression Rating Scale score >16)
• severe dysautonomia
• Cerebellar signs
• Babinski sign
• Strictly unilateral features after 3 years
• Hydrocephalus or intracranial lesion on neuroimaging
• We also excludes patients with intracranial metallic devices or with pacemakers or any other device.

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: Real rTMS; Real rTMS high frequency stimulation (25 HZ), with intensity of 80% of resting motor threshold detected from the hand motor area, with total 2000 pulses for each hemisphere on the hand motor area for 10 consecutive sessions totally over period of 10 days.	Device: repetitive Transcranial Magnetic Stimulation; By defining intensity of 80% of the resting Motor Threshold detected from motor area for Rt Abductor digiti minimi (ADM), we will apply repetitive Transcranial Magnetic Stimulation (rTMS) using 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magnetic Stimulator with high frequency (25Hz), Stimuli will be delivered for total 2000 pulse (divided on 50 trains with 40 pulses per train with inter-train interval 30 seconds) for each hemisphere (coil placed tangential over the optimal position of hand motor area detected for Real group and the same coil placed perpendicular with hand of coil pointing upward over occipital cortex for Sham group). Sessions will be consecutive for ten days period with repetition of consecutive 5 sessions as boosting doses on 5 days period over the follow up visits every month for the next 3 months.; Other Names: rTMS
Sham Comparator: Sham rTMS; Sham rTMS high frequency stimulation (25 HZ), with intensity of 80% of resting motor threshold detected from the hand motor area, with total 2000 pulses for each hemisphere with coil perpendicular on scalp for 10 consecutive sessions totally over period of 10 days.	Device: repetitive Transcranial Magnetic Stimulation; By defining intensity of 80% of the resting Motor Threshold detected from motor area for Rt Abductor digiti minimi (ADM), we will apply repetitive Transcranial Magnetic Stimulation (rTMS) using 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magnetic Stimulator with high frequency (25Hz), Stimuli will be delivered for total 2000 pulse (divided on 50 trains with 40 pulses per train with inter-train interval 30 seconds) for each hemisphere (coil placed tangential over the optimal position of hand motor area detected for Real group and the same coil placed perpendicular with hand of coil pointing upward over occipital cortex for Sham group). Sessions will be consecutive for ten days period with repetition of consecutive 5 sessions as boosting doses on 5 days period over the follow up visits every month for the next 3 months.; Other Names: rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in Mini Mental State Examination (MMSE)	any changes in MMSE along the course of follow up (baseline, post treatment, one, two and three months later). Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.	three months
changes in Montreal cognitive assessment scale (MoCA)	any changes of Montreal cognitive assessment scale (MoCA)along the course of follow up (baseline, post treatment, one, two and three months later). MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. In a study, people without cognitive impairment scored an average of 27.4; people with mild cognitive impairment (MCI) scored an average of 22.1; people with Alzheimer's disease scored an average of 16.2.	3 months
Event related potential P300	changes in Event related potential P300 latency and amplitude (pre sessions -post sessions)As cognitive impairment elongates the P300 latency, we hypotheses that P300 could be a monitoring biomarker for rTMS effect, on cognitive function.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
motor part of Unified Parkinson's disease rating scale (UPDRS)	changes in motor part of Unified Parkinson's disease rating scale (UPDRS)along the course of follow up (baseline, post treatment, one, two and three months later)	3 months
changes in cortical excitability	changes in cortical excitability (baseline, post treatment)	10 days

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Eman Khedr, professor, Neurology Department, Faculty of Medicine, Assiut University

Publications and helpful links

General Publications

• Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003 Mar;60(3):387-92. doi: 10.1001/archneur.60.3.387.
• Aarsland D, Bronnick K, Fladby T. Mild cognitive impairment in Parkinson's disease. Curr Neurol Neurosci Rep. 2011 Aug;11(4):371-8. doi: 10.1007/s11910-011-0203-1.
• Aarsland D, Ballard C, Rongve A, Broadstock M, Svenningsson P. Clinical trials of dementia with Lewy bodies and Parkinson's disease dementia. Curr Neurol Neurosci Rep. 2012 Oct;12(5):492-501. doi: 10.1007/s11910-012-0290-7.
• Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, Mitra T, Frades-Payo B, Tluk S, Ruessmann A, Odin P, Macphee G, Stocchi F, Ondo W, Sethi K, Schapira AH, Martinez Castrillo JC, Martinez-Martin P. The nondeclaration of nonmotor symptoms of Parkinson's disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord. 2010 Apr 30;25(6):704-9. doi: 10.1002/mds.22868.
• Khedr EM, Mohamed KO, Ali AM, Hasan AM. The effect of repetitive transcranial magnetic stimulation on cognitive impairment in Parkinson's disease with dementia: Pilot study. Restor Neurol Neurosci. 2020;38(1):55-66. doi: 10.3233/RNN-190956.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): June 15, 2019
• Study Completion (Actual): June 15, 2019

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 15, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Cognition Disorders; Parkinson Disease; Cognitive Dysfunction
• Other Study ID Numbers: rTMS and cognition in PD

Drug and device information, study documents

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