Brain Tumors, Motor Deficit, Quality of Life, Transcranial Magnetic Stimulation
Conditions
Keywords
Transcranial magnetic stimulation, Brain tumor, Post-operative muscle weakness, Quality of life, Brain tumor surgery, TMS, Post-craniotomy
Brief summary
When doctors perform surgery to remove brain tumors, the goal is to take out as much of the tumor as possible while keeping the patient's brain functions intact. However, sometimes patients have trouble with movements like walking or using their hands after surgery. One reason for this is unintentional damage to important areas of the brain during the operation. A technique called Transcranial Magnetic Stimulation (TMS) might help patients recover these lost abilities faster. The investigators are conducting a study to see if TMS can help patients recover their movement abilities after brain tumor surgery. TMS uses magnetic pulses to stimulate specific parts of the brain. In this study, the investigators will treat six patients with TMS once per day for three days in a row. Three patients with recent movement difficulties one to two weeks after surgery will be recruited for this study; they will also receive physical therapy. An additional three patients with persisting movement difficulties up to three years after tumor surgery will also be recruited for this study, regardless of whether or not they receive physical therapy. The investigators will use two standard tests to see how well patients can move before and after the TMS treatment. These tests will help the investigators understand if TMS is making a difference in their recovery.
Detailed description
This study is a prospective single-center non-randomized open label pilot trial to assess the safety and feasibility of rTMS for brain tumor patients with acute or chronic post-operative motor deficits. The study will prospectively enroll 3 patients for postoperative TMS. Each treatment period will consist of 1 week, including 3 consecutive days of treatment within this week. Participants will receive inhibitory continuous theta burst stimulation (cTBS) to Brodmann cortical areas which correspond to the contralesional supplementary motor area (SMA), pre-central gyrus (PrCG) and post-central gyrus (PoCG) to side of paresis and excitatory intermittent theta burst stimulation (iTBS) to Brodmann cortical areas which correspond to the ipsilesional SMA, PrCG and PoCG. This treatment will be performed for 3 consecutive days in conjunction with and without standard-of-care physiotherapy for patients with acute post-operative motor deficits and chronic post-operative motor deficits, respectively. TMS treatment protocols will include those which have already been established in the literature and validated for use in neurological patients, including those with brain tumors, with adaptations in other clinics as well. These protocols have been shown to have a significant safety profile. Post-treatment assessments will occur at 1 week, 1 month, 3 months and 6 months. Follow-up assessments will occur through patient visits, which may include standard-of-care visits for patients in the acute post-operative setting.
Interventions
DEVICETranscranial magnetic stimulation (TMS)
Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique. This intervention involves a form of repetitive TMS (rTMS) known as continuous theta burst stimulation (cTBS) to Brodmann cortical areas, which correspond to the contralesional supplementary motor area (SMA), pre-central gyrus (PrCG), and post-central gyrus (PoCG) to side of paresis and excitatory intermittent theta burst stimulation (iTBS) to Brodmann cortical areas, which correspond to the ipsilesional SMA, PrCG and PoCG.
Sponsors
Brian J.Gill
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged 22-65 years old who have undergone surgical resection for a brain tumor. 2. Patients undergoing any form of prior therapy, other than previous TMS therapy, will be considered. 3. Patients who present with sustained postoperative motor deficits at 1-2 weeks postoperatively as defined by the presence of British Medical Research Council (MRC) motor scores of 3/5 or less, or a sustained decrement by one point on the MRC score in the affected extremity. 4. Patients who present within three years of surgery with chronic, persistent motor-functional deficits will be included to demonstrate generalizability of safety and efficacy in neurosurgery patients with chronic deficits. 5. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Patients with any clinical history of seizures. 2. Patients with implanted devices (e.g., pacemakers, implanted stimulators, intracranial electrodes, cochlear implants). 3. Patients who have undergone a brain biopsy alone without resection. 4. Patients with postoperative cognitive deficits as defined by a Mini Mental State Examination score \<26. 5. History of bipolar disorder. 6. Pregnant or breast-feeding individuals. 7. Active suicidal ideation or plan as assessed by the Columbia Suicide Severity Rating Scale. 8. History of moderate to severe heart disease. 9. History of other neurological conditions defined by structural cerebral damage (e.g., stroke, multiple sclerosis, other neurodegenerative diseases, meningoencephalitis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events and serious adverse events experienced following transcranial magnetic stimulation sessions | Up to 2 weeks | Safety will be determined by the rate of adverse events that occur within one week following completion of the transcranial magnetic stimulation protocol. Adverse events (AEs) and serious adverse events (SAEs) will be reported, along with their 95% confidence intervals. |
| Feasibility of transcranial magnetic stimulation in postcraniotomy patients who present with either acute or chronic deficits | Up to 2 weeks | Feasibility, as assessed by initial motor recovery, will be measured by participants' British Medical Research Council (MRC) score one week after protocol completion. For the primary feasibility endpoint, mean MRC scores will be reported before and one week after protocol completion. The MRC score ranges from 0 to 5, with a higher score indicating better muscle strength. A paired t-test will be used to determine whether the mean MRC score significantly increases after the TMS treatment. A 20-point increase is anticipated in the mean MRC score one week after protocol completion compared to before TMS treatment. Assuming a pooled standard deviation of 15 points, the test has a power of 0.87 to reject the null hypothesis with 6 evaluable patients and a significance level of 0.05. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Motor recovery as evaluated by change from baseline in the Medical Research Council (MRC) Scale for Muscle Strength | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on motor recovery as assessed by change from baseline in the Medical Research Council (MRC) Scale for Muscle Strength. The MRC Scale ranges from Grade 0 (no visible contraction) to Grade 5 (normal muscle strength), with a higher score indicating better muscle strength. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Motor recovery as evaluated by change from baseline in the 10-Meter Walk Test (10MWT) | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on motor recovery as assessed by change from baseline in The 10-Meter Walk Test (10MWT). The 10MWT measures short-distance walking speed in meters/second over a distance of six meters. Higher speeds indicate better functional mobility, vestibular function, and gait. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Motor recovery as evaluated by change from baseline in The Box and Block Test (BBT) | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on motor recovery as assessed by change from baseline in the Box and Block Test (BBT). The BBT measures unilateral gross manual dexterity and is scored based upon the number of blocks a participant can transfer from one compartment of a box to another compartment within 60 seconds. Higher scores indicate better motor function in gross manual dexterity. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Motor recovery as evaluated by change from baseline in the Barthel Index (BI) | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on motor recovery as assessed by change from baseline in the Barthel Index (BI). The BI measures ability to perform activities of daily living (ADLs) and mobility on a ten-item scale: (1) feeding, (2) bathing, (3) grooming, (4) dressing, (5) bowel continence, (6) bladder continence, (7) toilet use, (8) transfers from bed to chair and back, (9) mobility on level surfaces, and (10) mobility on stairs. The total score range is 0 to 100 across all 10 domains, with lower scores indicating greater dependency or impaired functional status. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Quality of life as evaluated by change from baseline in the QLQ-BN20 | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on quality of life as assessed by change from baseline in the QLQ-BN20 questionnaire. The QLQ-BN20 is a quality-of-life survey validated for use in patients with brain tumors. The QLQ-BN20 consists of four multi-item scales: (1) future uncertainty (four items), (2) visual disorder (three items), (3) motor dysfunction (three items), and (4) communication deficit (three items). All items and scale scores are linearly transformed onto a 0 to 100-point scale, with higher scores signifying more severe symptoms and lower quality of life. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Quality of life as evaluated by change from baseline in the Functional Assessment of Cancer Therapy - Brain (FACT-Br) | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on quality of life as assessed by change from baseline in the Functional Assessment of Cancer Therapy - Brain (FACT-Br). The FACT-Br consists of the core FACT-General (FACT-G) questionnaire assessing more general domains of quality-of-life in addition to the brain tumor-specific scale. A total of 50 items is included across the following subscales: (1) physical well-being, (2) social/family wellbeing, (3) emotional well-being, (4) functional well-being, and (5) disease-specific concerns. Participants indicate the presence/severity of symptoms on a 5-point Likert Scale (0 to 4), with higher scores indicating more present/severe symptoms and lower quality of life. The total score range is 0 to 200. Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
| Quality of life as evaluated by change from baseline in the EQ-5D-5L | Baseline, 1 week, 1 month, 3 months, and 6 months post-intervention | Efficacy of transcranial magnetic stimulation on quality of life as assessed by change from baseline in the EQ-5D-5L. The EQ-5D-5L is a validated instrument that assesses quality of life using self-reported profile data and a subjective visual scale to capture participants' perceptions of their own health. The EQ-5D-5L profile data is measured across five dimensions: (1) mobility, (2) usual activities, (3) self-care, (4) pain and discomfort, and (5) anxiety and depression. Each dimension is measured on a 5-point Likert scale, with 1 indicating no issues in a particular domain and 5 indicating extreme issues. Scores across all five dimensions form a five-digit "value set," which are then converted to a single number (i.e., EQ-5D values) using a weighting system. The total score ranges from 0 (indicating death) to 1 (indicating full health). Scores will be recorded pre-intervention and then at 1 week, 1 month, 3 months, and 6 months post-intervention. |
Countries
United States
Contacts
CONTACTResearch Nurse Navigator
PRINCIPAL_INVESTIGATORBrian J Gill, MD
Columbia University
Outcome results
None listed