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CTRI Number  CTRI/2025/12/098484 [Registered on: 04/12/2025] Trial Registered Prospectively
Last Modified On: 02/12/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Other (Specify) [Transcranial magnetic stimulation ]  
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Magnetic stimulation of the Brain for treating walking and thinking problems in PSP (Progressive Supranuclear Palsy). 
Scientific Title of Study   Blinded Randomized Controlled Trial of rTMS to the Dorsolateral Prefrontal Cortex in Progressive Supranuclear Palsy: Effects on Gait, Cognition, and Brain Perfusion 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Yaranagula Sai Deepak  
Designation  Director, Parkinsons and Movement Disorders Clinic (PMDC), Citi Neuro Centre 
Affiliation  Citi Neuro Centre 
Address  Room 7, B3, PMDC, Dept of Neurology, Citi Neuro Centre, Number 12, Banjara Hills, Hyderabad, Telangana

Hyderabad
TELANGANA
500028
India 
Phone  9591865402  
Fax    
Email  sd1162010@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Yaranagula Sai Deepak  
Designation  Director, Parkinsons and Movement Disorders Clinic (PMDC), Citi Neuro Centre 
Affiliation  Citi Neuro Centre 
Address  Room 7, B3, PMDC, Dept of Neurology, Citi Neuro Centre, Number 12, Banjara Hills, Hyderabad, Telangana

Hyderabad
TELANGANA
500028
India 
Phone  9591865402  
Fax    
Email  sd1162010@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Yaranagula Sai Deepak  
Designation  Director, Parkinsons and Movement Disorders Clinic (PMDC), Citi Neuro Centre 
Affiliation  Citi Neuro Centre 
Address  Room 7, B3, PMDC, Dept of Neurology, Citi Neuro Centre, Number 12, Banjara Hills, Hyderabad, Telangana

Hyderabad
TELANGANA
500028
India 
Phone  9591865402  
Fax    
Email  sd1162010@gmail.com  
 
Source of Monetary or Material Support  
Citi Neuro Centre Foundation, Citi Neuro Centre, Number 12, near Shri Jagannath Temple, MLA Colony, Banjara Hills, Hyderabad, Telangana 500028 
 
Primary Sponsor  
Name  Citi Neuro Centre Foundation 
Address  Citi Neuro Centre, Number 12, near Shri Jagannath Temple, MLA Colony, Banjara Hills, Hyderabad, Telangana 500028 
Type of Sponsor  Private hospital/clinic 
 
Details of Secondary Sponsor  
Name  Address 
NIL   
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Yaranagula Sai Deepak   Citi Neuro Centre   Number 12, near Shri Jagannath Temple, MLA Colony, Banjara Hills, Hyderabad, Telangana 500028
Hyderabad
TELANGANA 
9591865402

sd1162010@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
CNC Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: G231||Progressive supranuclear ophthalmoplegia [Steele-Richardson-Olszewski],  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Transcranial Magnetic Stimulation  rTMS over left dorsolateral prefrontal cortex will be conducted using a high-frequency protocol (10 Hz), applying 60 trains of 50 pulses with a duration of 5 seconds and an intertrain interval of 25 seconds (3,000 pulses per session), at an intensity of 120% of the resting motor threshold. Over the course of 8 weeks, 25 sessions will be scheduled 
Comparator Agent  Transcranial Magnetic Stimulation  Sham Arm: Identical procedure using a sham coil that mimics sensation and sound without active stimulation. 
 
Inclusion Criteria  
Age From  40.00 Year(s)
Age To  80.00 Year(s)
Gender  Both 
Details  -Diagnosis of PSP according to MDS criteria
-Ability to stand unassisted for 30 seconds and able to walk independently
-MMSE 18 or more
-On stable treatment of anticholinergic, dopaminergic, serotonergic or NMDA antagonist medication
-Age 40–80 years
-Able to undergo MRI and rTMS
-Informed consent provided
 
 
ExclusionCriteria 
Details  -Contraindications to rTMS or MRI (e.g., metallic implants)
-Pregnancy
-History of cerebellar ataxia, SOL, hydrocephalus, SDH, Prior vestibular disease
-Sensory deficit in feet
-Epilepsy
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
Gait: Change in Time taken to walk 10 meters measured via video gait recording of Timed up and go test (TUG)

Cognition: Changes in Montreal Cognitive Assessment (MoCA) and Frontal assessment battery (FAB) scores 
2 months, 3 months, 4 months and 6 months 
 
Secondary Outcome  
Outcome  TimePoints 
-Change in number of Falls with falls diary
-Change in PSP rating scale
-Changes in Brain perfusion: ASL MRI to assess regional cerebral blood flow changes in relevant cortical and subcortical regions 
4 months  
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   15/12/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - YES
  1. What data in particular will be shared?
    Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

  2. What additional supporting information will be shared?
    Response -  Study Protocol
    Response -  Statistical Analysis Plan
    Response - Informed Consent Form
    Response - Clinical Study Report

  3. Who will be able to view these files?
    Response - Researchers who provide a methodologically sound proposal.

  4. For what types of analyses will this data be available?
    Response - To achieve aims in the approved proposal.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [sd1162010@gmail.com].

  6. For how long will this data be available start date provided 01-01-2028 and end date provided 31-12-2100?
    Response - Immediately following publication. No end date.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NIL
Brief Summary  

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique shown to be useful in treating a number of neuropsychiatric conditions including depression, neuropathic pain and Parkinson’s disease (PD). While in depression, rTMS is being increasingly used, its use in Parkinsonian syndromes has been impeded by lack of high-quality evidence. A few studies have explored rTMS in PD and atypical Parkinsonian syndromes such as Progressive supranuclear palsy (PSP). However, most studies are limited by small samples, inadequate dosage of intervention and lack of patho-physiological study correlates.

The use of rTMS in depression has gained widespread attention and acceptance. The runaway success of rTMS in major depressive disorder (MDD) is rooted in a firm biological basis with the dorsolateral prefrontal cortex (DLPFC) at its heart. In MDD, the left DLPFC is hypoactive and right DLPFC is hyperactive. Therefore, logic dictates that improvement in activity of left DLPFC or inhibition of right DLPFC activity would be able to reverse depression. rTMS is capable of neuro stimulation at high frequency and inhibition at low frequency. Taken together, rTMS is a convenient non-invasive tool that has tremendous potential to modulate neural circuits in depression and this has been applied by multiple researchers.

DLPFC, especially the left DLPFC, is a large specialized area of the prefrontal cortex with a significant role in maintaining working memory. Working memory is the ability to hold information online for a few seconds to minutes. This is essential to keep track of ongoing activity, the components of activity that have been executed and the pending components that have to be executed in order to complete a task. Working memory research has been predominantly focused on specific sensory modalities such as visuospatial (visual) working memory or phonological (verbal) working memory. Recent research has shown evidence to suggest existence of motor working memory along similar lines. Deficits in working memory have been shown to be associated with increased falls in elderly. This is an important realization as interventions improving cognition may improve falls and gait.

In general, older adults demonstrate relative hyperactivity of brain during a given task when compared to younger individuals. This is thought to be a compensatory phenomenon as older brains recruit additional brain regions to compensate for age related degeneration. The left DLPFC plays an important role in gait. In elderly, there is a relative hyperactivity of left DLPFC during walking. By corollary, dysfunction of DLPFC can therefore lead to abnormalities in walking and gait, and by extension can lead to increased risk of falls.

In PSP, there is evidence to suggest dysfunction of left DLPFC. A recent study evaluated the effects of transcranial direct current stimulation (tDCS) over left DLPFC in PSP and found it to be ineffective in improving cognitive and motor functions. However, the study was severely limited with only 16 subjects receiving real tDCS for only 5 days per week for 2 weeks. While there have been rTMS studies on gait in PSP, none of them evaluated DLPFC stimulation. Both these studies were limited by small sample size and limited rTMS dosage. Therefore, a sufficiently powered study with appropriate sample size and appropriate rTMS dosage on DLPFC in PSP is lacking. This study aims to assess the efficacy of DLPFC rTMS in improving gait and cognition, and to evaluate associated changes in cerebral perfusion using arterial spin labeling (ASL) MRI in PSP patients.

 
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