rTMS Therapy for Primary Orthostatic Tremor

NCT02441985 | Completed Results DMC

• 1 other identifier: IRB201500347
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Primary orthostatic tremor(POT) is a rare progressive functionally disabling tremor disorder. The characteristic features of POT are symptoms of unsteadiness in legs reported by patients when they are standing and improvement of symptoms upon walking and sitting. Due to the limited success of other treatment options there is a clear merit in continuing efforts to explore and investigate novel treatment modalities. Transcranial magnetic stimulation (TMS) is a well-established physiological tool to understand brain function. When repetitious TMS pulses are delivered to a specific target at predefined stimulation parameters, it is referred to as rTMS therapy.The investigators propose a novel approach to investigate the clinical and physiological effects of low frequency rTMS therapy in POT. The overarching hypothesis of this study is that low frequency rTMS therapy delivered to the cerebellum will modulate the cerebellar excitability and result in clinical improvements.In order to determine the physiological effects related to rTMS, the tremor physiology will also be recorded with surface electromyography (EMG). The investigator will also record the changes in cerebellum excitability in response to rTMS using cerebello-cortical inhibition (CBI), a well-established TMS parameter.

Conditions

Primary Orthostatic Tremor

Keywords

Primary orthostatic tremor

Outcome Measures

Primary Outcomes (1)

• Change in Fullerton Advanced Balance (FAB) Scale Total Score After rTMS

  The Fullerton Advanced Balance (FAB) Scale is a clinical assessment of balance ability and fall risk. Participants complete 10 physical activity challenges while observed, and their performance is rated on a 0-4 scale, where a higher score a greater ability to balance. Each item is then summed to generate a Total Score, ranging from 0-40, where a higher total score indicates greater overall balance and lower likelihood of fall risk. The reported measure is the change in the FAB Total Score from before and after, where a positive value implies improvement in balance, a negative value indicates a worsening of balance, and 0 indicates no change.

  Pre- to Post-Intervention, on average 3 hours

Other Outcomes (2)

• Standing Duration

  Pre- to Post-Intervention, on average 3 hours apart

• Timed "Up & Go" Test (TUG) Test

  Pre- to Post-Intervention

Study Arms (2)

Real rTMS Stimulation

EXPERIMENTAL

rTMS will be delivered over each cerebellar hemisphere, using a 70mm figure-of-eight coil connected to a Magstim RapidStim2 machine while positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. The inion will be taken as the boundary between the posterior cerebellum and the occipital cortex. Therefore the area stimulated will be caudal to the inion to stimulate the posterior cerebellum.

Device: Magstim RapidStim2; Other: Fullerton Advanced Balance (FAB) Scale; Other: Timed "Up & Go" Test (TUG) test; Other: 10m walk test; Other: Tremor electrophysiology; Other: Cerebellar-brain Inhibition (CBI)

Sham rTMS Stimulation

SHAM COMPARATOR

Patients randomized to receive sham treatment will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham Magstim RapidStim2 Placebo which produces discharge noise and vibration similar to the real coil without stimulating the cerebral cortex. However, in addition to obvious coil discharge noise, rTMS also causes electrical stimulation of the scalp. The investigator will simulate this experience by attaching surface electrodes underneath the sham coil and in contact with the scalp. The investigator will use an electromyography to administer electrical shocks to the scalp simultaneous to each simulated rTMS train.

Device: Sham Magstim RapidStim2; Other: Fullerton Advanced Balance (FAB) Scale; Other: Timed "Up & Go" Test (TUG) test; Other: 10m walk test; Other: Tremor electrophysiology; Other: Cerebellar-brain Inhibition (CBI)

Interventions

Magstim RapidStim2 DEVICE

Application of repetitious transcranial magnetic stimulation (TMS) pulses using Magstim RapidStim2 to a specific brain target at predefined stimulation parameters.

Real rTMS Stimulation

Sham Magstim RapidStim2 DEVICE

Same procedure as real rTMS without stimulating the cerebral cortex.

Sham rTMS Stimulation

Fullerton Advanced Balance (FAB) Scale OTHER

All participants will receive a clinical assessment of balance ability and fall risk.

Real rTMS Stimulation; Sham rTMS Stimulation

Timed "Up & Go" Test (TUG) test OTHER

All participants will receive a clinical assessment of basic mobility skills by using the TUG test.

Real rTMS Stimulation; Sham rTMS Stimulation

10m walk test OTHER

All participants will receive a clinical assessment of walking speed by using the walk test.

Real rTMS Stimulation; Sham rTMS Stimulation

Tremor electrophysiology OTHER

All participant tremors will by analyzed using an EMG system

Real rTMS Stimulation; Sham rTMS Stimulation

Cerebellar-brain Inhibition (CBI) OTHER

All participants will have a measure of the cerebellar-brain inhibition (CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Real rTMS Stimulation; Sham rTMS Stimulation

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Potential participants will be diagnosed with Primary orthostatic tremor (POT) and be recruited through IRB approved database maintained by the Movement Disorders Center

You may not qualify if:

• Pregnancy
• Active seizure disorder
• Significant cognitive impairment
• Presence of a metallic body such as pacemaker, implants, prosthesis,artificial limb or joint, shunt, metal rods and hearing aid

Sponsors & Collaborators

• University of Florida: lead
• National Organization for Rare Disorders: collaborator
• Neuronetics: collaborator

Study Sites (1)

Center for Movement Disorders and Neurorestoration

Gainesville, Florida, 32607, United States

Location

Related Publications (20)

• Wagle Shukla A, Vaillancourt DE. Treatment and physiology in Parkinson's disease and dystonia: using transcranial magnetic stimulation to uncover the mechanisms of action. Curr Neurol Neurosci Rep. 2014 Jun;14(6):449. doi: 10.1007/s11910-014-0449-5.

  PMID: 24771105 BACKGROUND

• Udupa K, Chen R. Motor cortical plasticity in Parkinson's disease. Front Neurol. 2013 Sep 4;4:128. doi: 10.3389/fneur.2013.00128.

  PMID: 24027555 BACKGROUND

• Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation over the cerebellum in humans. Ann Neurol. 1995 Jun;37(6):703-13. doi: 10.1002/ana.410370603.

  PMID: 7778843 BACKGROUND

• Stacy MA, Elble RJ, Ondo WG, Wu SC, Hulihan J; TRS study group. Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord. 2007 Apr 30;22(6):833-8. doi: 10.1002/mds.21412.

  PMID: 17343274 BACKGROUND

• Mathias S, Nayak US, Isaacs B. Balance in elderly patients: the "get-up and go" test. Arch Phys Med Rehabil. 1986 Jun;67(6):387-9.

  PMID: 3487300 BACKGROUND

• Ugawa Y, Terao Y, Hanajima R, Sakai K, Furubayashi T, Machii K, Kanazawa I. Magnetic stimulation over the cerebellum in patients with ataxia. Electroencephalogr Clin Neurophysiol. 1997 Sep;104(5):453-8. doi: 10.1016/s0168-5597(97)00051-8.

  PMID: 9344082 BACKGROUND

• Roth BJ, Saypol JM, Hallett M, Cohen LG. A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroencephalogr Clin Neurophysiol. 1991 Feb;81(1):47-56. doi: 10.1016/0168-5597(91)90103-5.

  PMID: 1705219 BACKGROUND

• Amassian VE, Cracco RQ, Maccabee PJ, Cracco JB. Cerebello-frontal cortical projections in humans studied with the magnetic coil. Electroencephalogr Clin Neurophysiol. 1992 Aug;85(4):265-72. doi: 10.1016/0168-5597(92)90115-r.

  PMID: 1380914 BACKGROUND

• Cohen LG, Roth BJ, Nilsson J, Dang N, Panizza M, Bandinelli S, Friauf W, Hallett M. Effects of coil design on delivery of focal magnetic stimulation. Technical considerations. Electroencephalogr Clin Neurophysiol. 1990 Apr;75(4):350-7. doi: 10.1016/0013-4694(90)90113-x.

  PMID: 1691084 BACKGROUND

• Werhahn KJ, Taylor J, Ridding M, Meyer BU, Rothwell JC. Effect of transcranial magnetic stimulation over the cerebellum on the excitability of human motor cortex. Electroencephalogr Clin Neurophysiol. 1996 Feb;101(1):58-66. doi: 10.1016/0013-4694(95)00213-8.

  PMID: 8625878 BACKGROUND

• Hashimoto M, Ohtsuka K. Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man. Brain. 1995 Oct;118 ( Pt 5):1185-93. doi: 10.1093/brain/118.5.1185.

  PMID: 7496779 BACKGROUND

• Deuschl G, Lucking CH, Quintern J. [Orthostatic tremor: clinical aspects, pathophysiology and therapy]. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb. 1987 Mar;18(1):13-9. German.

  PMID: 3106000 BACKGROUND

• Heilman KM. Orthostatic tremor. Arch Neurol. 1984 Aug;41(8):880-1. doi: 10.1001/archneur.1984.04050190086020.

  PMID: 6466163 BACKGROUND

• Espay AJ, Duker AP, Chen R, Okun MS, Barrett ET, Devoto J, Zeilman P, Gartner M, Burton N, Miranda HA, Mandybur GT, Zesiewicz TA, Foote KD, Revilla FJ. Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: preliminary observations. Mov Disord. 2008 Dec 15;23(16):2357-62. doi: 10.1002/mds.22271.

  PMID: 18759339 BACKGROUND

• Guridi J, Rodriguez-Oroz MC, Arbizu J, Alegre M, Prieto E, Landecho I, Manrique M, Artieda J, Obeso JA. Successful thalamic deep brain stimulation for orthostatic tremor. Mov Disord. 2008 Oct 15;23(13):1808-11. doi: 10.1002/mds.22001.

  PMID: 18671286 BACKGROUND

• Benito-Leon J, Rodriguez J. Orthostatic tremor with cerebellar ataxia. J Neurol. 1998 Dec;245(12):815. doi: 10.1007/s004150050294. No abstract available.

  PMID: 9840357 BACKGROUND

• Setta F, Jacquy J, Hildebrand J, Manto MU. Orthostatic tremor associated with cerebellar ataxia. J Neurol. 1998 May;245(5):299-302. doi: 10.1007/s004150050222. No abstract available.

  PMID: 9617712 BACKGROUND

• Wills AJ, Thompson PD, Findley LJ, Brooks DJ. A positron emission tomography study of primary orthostatic tremor. Neurology. 1996 Mar;46(3):747-52. doi: 10.1212/wnl.46.3.747.

  PMID: 8618676 BACKGROUND

• Manto MU, Setta F, Legros B, Jacquy J, Godaux E. Resetting of orthostatic tremor associated with cerebellar cortical atrophy by transcranial magnetic stimulation. Arch Neurol. 1999 Dec;56(12):1497-500. doi: 10.1001/archneur.56.12.1497.

  PMID: 10593305 BACKGROUND

• Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.

  PMID: 9827589 BACKGROUND

MeSH Terms

Conditions

Primary orthostatic tremor

Interventions

Weights and Measures

Intervention Hierarchy (Ancestors)

Investigative Techniques

Results Point of Contact

• Title: Aparna Wagle Shukla
• Organization: University of Florida

aparna.shukla@neurology.ufl.edu

3522945400

Study Officials

• Aparna Wagle-Shukla, M.D.

  Center for Movement Disorders and Neurorestoration

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2015
• First Posted: May 12, 2015
• Study Start: August 1, 2015
• Primary Completion: January 8, 2019
• Study Completion: January 8, 2019
• Last Updated: April 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-03

Locations

US (1)