Cerebellar iTBS in Patients With Disorders of Consciousness (CTPDOC)

• ClinicalTrials.gov Identifier: NCT05558930
• Recruitment Status: Recruiting
• First Posted: September 28, 2022
• Last Update Posted: September 28, 2022
• Sponsor: Xijing Hospital
• Information provided by (Responsible Party): Xijing Hospital

Tracking Information

• First Submitted Date: September 1, 2022
• First Posted Date: September 28, 2022
• Last Update Posted Date: September 28, 2022
• Actual Study Start Date: April 29, 2022
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 25, 2022)

Change in CRS-R Total Scores [ Time Frame: Baseline and directly after 5 sessions of iTBS and sham stimulation（5 days） ]

Whether bilateral cerebellar iTBS would improve consciousness in enrolled patients. CRS-R total score is used to measure level of consciousness of disorder.The coma recovery scale-revised(CRS-R) consists of six subscales addressing auditory, visual, motor, verbal, communication, and arousal functions.The lowest item on each subscale represents reflexive activity and the highest item represents cognitively mediated behavior. Maximum scores of each subscale are summed to obtain the total score (from 0 to 23).The score for each subscale is based on the presence or absence of a specific behavioral response to a sensory stimulus (higher scores are better).

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 25, 2022)

• Change in CRS-R Subscale Scores [ Time Frame: Baseline and directly after 5 sessions of iTBS and sham stimulation（5 days） ]
  The coma recovery scale-revised(CRS-R) consists of six subscales addressing auditory, visual, motor, verbal, communication, and arousal functions.The lowest item on each subscale represents reflexive activity and the highest item represents cognitively mediated behavior. The score for each subscale is based on the presence or absence of a specific behavioral response to a sensory stimulus (higher scores are better).
• Change of Influence on EEG [ Time Frame: Baseline and after 5 sessions of iTBS and sham stimulation（5 days） ]
  EEG will be monitored on the first and fifth sessions of both iTBS and sham stimulation, from 20 minutes before the start of stimulation until 30 minutes after the end of stimulation.
• Influence of time since insult on the results [ Time Frame: Participants will be followed for the duration of 0.5 year ]
  Glasgow Outcome Scale-Extended(GOSE) score will be assessed at 3 and 6 months of enrollment.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cerebellar iTBS in Patients With Disorders of Consciousness
• Official Title: MRI-navigated Cerebellar Intermittent Theta-Burst Stimulation（iTBS）in Patients With Disorders of Consciousness
• Brief Summary: Previous studies showed the excitatory effect of cerebellar transcranial magnetic stimulation(TMS) on motor cortex.Investigator evaluate the effects of bilateral cerebellar TMS on Coma Recovery Scale-Revised (CRS-R) scores in patients with disorders of consciousness(DOC) in a randomized, double-blinded, sham-controlled, crossover experimental design.

Detailed Description

Patients with disorders of consciousness(DOC) resulting from severe brain injury greatly burden caregivers, health care facilities, and society. However, there is no definitively effective treatment for patients with DOC.

Previous studies showed the excitatory effect of cerebellar transcranial magnetic stimulation(TMS) on motor cortex through the dentato-rubro-thalamic tract. Investigators aim to validate the effect of 5 consecutive sessions of intermittent theta-burst stimulation(iTBS) of bilateral cerebellar on level of consciousness of patients in vegetative state(VS)/unresponsive awakening state(UWS)or minimally conscious (MCS) state in a randomized, double-blinded, sham-controlled, crossover study.

TMS is a non-invasive and safe neural regulatory approach that is widely used in depression, schizophrenia, stroke, and Parkinson's disease.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

A randomized double-blinded, sham-controlled, crossover study design is used to investigate the effects of bilateral cerebellar iTBS on patients with prolonged DOC in a VS/UWS or in a MCS state. We prospectively recruit 44 patients in VS/UWS or MCS state. Each patient will receive bilateral cerebellar iTBS and sham stimulation in random order, one session per day for 5 consecutive days, separated by a 5-day washout. TMS is performed by personalized neuro-navigation to target the cerebellar dentate nucleus. The primary research outcome is whether bilateral cerebellar iTBS, as compared to sham stimulation, will improve consciousness (as measured by changes in CRS-R total scores) in VS/UWS and MCS patients. Secondary research outcome is evaluated by Electroencephalogram(EEG), CRS-R subscore, and Glasgow Outcome Scale-Extended(GOSE) score at 3 and 6 months of enrollment.

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment

Condition

• Disorder of Consciousness
• Vegetative State
• Minimally Conscious State

Intervention

• Device: iTBS stimulation
  standard iTBS burst pattern:3 pulses at 50-Hz repeated at a rate of 5-Hz; 20 trains of 10 bursts given with 8-s intervals. 600 pulses on both side of cerebellar with an interval of 5 minutes.
• Device: sham stimulation
  Participants receive a sound stimulation with the same pattern with iTBS stimulation,but without magnetic field

Study Arms

• Experimental: iTBS stimulation
  Participants receive iTBS stimulation of bilateral cerebellar one session per day for 5 consecutive days.
  Intervention: Device: iTBS stimulation
• Sham Comparator: sham stimulation
  Participants receive sham stimulation of bilateral cerebellar one session per day for 5 consecutive days.
  Intervention: Device: sham stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 25, 2022): 44
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. VS/UWS or MCS according to diagnostic criteria
2. Age ≥18 years
3. Written informed consent obtained

Exclusion Criteria:

1. Patients in coma
2. Brain injury <1week
3. Presence of metallic hardware in close contact to the discharging coil（such as cochlear implants, or an Internal Pulse Generator or medication pumps）
4. Patients with high risks according to standard questionnaire to screen transcranial magnetic stimulation(TMS) candidates

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rong Chen; 18292575563; cmuchenrong@126.com

Contact: Wen Jiang

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05558930
• Other Study ID Numbers: 20222028
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Xijing Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Xijing Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Xijing Hospital
• Verification Date: May 2022