Gait Disorders, Neurologic
Conditions
Brief summary
Dopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait, balance problems and other gait issues directly impacts patients' quality of life. Experimental epidural spinal cord stimulation studies have suggested positive effects on locomotion among PD patients, but the effects of non invasive stimulation have never been explored.
Detailed description
The present study is a randomized, double-blind, placebo-controlled, parallel, phase II clinical trial that will assess the efficacy and safety of transcutaneous magnetic spinal cord stimulation in PD patients who have gait and balance changes refractory to dopaminergic therapy.
Interventions
DEVICENon-invasive magnetic stimulation of the spinal cord
Non-invasive transcutaneous magnetic stimulation of the dorsal spine will be applied by placing a circular magnetic coil (Magventure®️ MagPro®️ R20) on the skin, in the upper thoracic region (chest level T2-T3). The stimulation intensity will represent 100% of the motor threshold. The intermittent theta burst stimulation protocol will consist of 20 stimulation trains, with an interval of 8 seconds between trains, each train will have 20 bursts, and each burst will have 3 pulses at 50 Hz repeated at 5 Hz. In total, 1200 pulses will be applied for 3 minutes and 58 seconds
OTHERCoil will not be connected to the stimulation device
coil will not be connected to the stimulation device, and another active coil will be positioned about 15cm behind, far from its field of view, to provide idea from the sound stimulus that is being stimulated
Sponsors
University of Sao Paulo General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The random sequence will be generated by a computer program (randomization.com) using randomly exchanged blocks (size of four per block, active ratio / placebo 1: 1). Randomization will be stratified according to the severity of symptoms (TUG\> 33 seconds = severe group; TUG ≤ 33 seconds = light group). The researchers will be specifically instructed not to break the randomization schedule in any way. Different researchers will carry out randomization, clinical evaluation and stimulation. Patients will be blinded to randomization.
Intervention model description
Study is a randomized, double-blind, placebo-controlled, parallel, phase II clinical trial
Eligibility
Sex/Gender
ALL
Age
21 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women (not pregnant) aged between 21 and 80 years old; 2. Participants with idiopathic Parkinson's disease in Hoehn Yahr stages between 2 and 4 (moderate disease) during off-medication, whose primary symptom includes change in gait and / or balance (score equal to or greater than 1 in subitem 2.12 of the MSD scale -UPDRS \[gait and balance\]). The participant must also present freezing (block) of gait (score equal to or greater than 1 in sub-item 2.13 of the MSD-UPDRS scale - freezing). Patients should experience the above symptoms even though they are optimized from the medication point of view. The criteria for being optimized will be defined by a neurologist specialized in movement disorders who will evaluate the case. The presence of freezing will be confirmed through a specific scale (FOG score). 3. Mini-examination of mental status greater than or equal to 24 points; 4. Able to give informed consent in accordance with institutional policies; 5. Able to meet all testing and monitoring requirements, as defined by the study protocol;
Exclusion criteria
1. Patients with unstabilized psychiatric comorbidities 2. Impossibility to consent to your participation in the study. 3. Patients with uncontrolled infection or other pre-existing uncontrolled medical conditions (eg, decompensated diabetes, high blood pressure, pneumo or symptomatic heart disease). 4. Concomitant treatment with other experimental drugs. 5. Pregnant or breastfeeding women. 6. Presence of chronic pain in the lower limbs. 7. Patients who are unable to walk without assistance (cane, crutch, walker) or help from another person when they are without their medications for Parkinson's disease (off-medication).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TUG | Post-stimulation: immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | The primary outcome will be the change in gait speed between pre-stimulation and post-stimulation conditions between the two groups (active and placebo) assessed using the 5-meter total Timed Up and Go Test (TUG). Mixel model ANOVA, with TUG as the dependent variable, and time and group as independent variables -'group' would have two levels ('active' and 'placebo'). Our alternative hypothesis is that 'the time vs. group' interaction effect is significant. Then we should use post hoc statistical tests to explore our data further and to compare the effects of active versus placebo at different time levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary outcomes will be the change on other gait measures, gait speed. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | Evaluate the gait speed through measurements obtained through sensors for gait, during the gait of five meters. |
| Secondary outcomes will be the effects of stimulation on other gait measures, step length, stride length and step width. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | Evaluate step length, stride length and step width through measurements obtained through sensors for gait, during the gait of five meters. |
| Secondary outcomes will be the effects of stimulation on other gait measures, cadencia. | Baseline, immediately after the fifth day of stimulation, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | Evaluate the cadencia through measurements obtained through sensors for gait, during the gait of five meters. |
| Secondary outcomes will be the effects of stimulation on balance after noninvasive magnetic stimulation of the dorsal spine in patients with parkinson's disease. | Baseline, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | Evaluate the improvement of the balance through the application of questionnaires,which will be the Activities-specific Balance Confidence Scale (ABC) and Falls Efficacy Scale (FES I). |
| Determination of possible adverse effects of noninvasive magnetic stimulation of the dorsal spine in patients with parkinson's disease. | Immediately after the fifth day of stimulation, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | The patient will be actively questioned about the appearance of adverse effects of noninvasive stimulation of the dorsal cord. |
| Assess the effects of transcutaneous magnetic stimulation of the dorsal cord on quality of life in patients with parkinson's disease | Baseline, seven days after finishing the stimulation, twenty-eight days after finishing the stimulation. | The questionnaire Parkinson Disease Questionnaire-39 (PDQ-39) will be applied. |
| To evaluate the effects of noninvasive stimulation of the dorsal cord in the presence of freezing gait, through the application of questionnaires. | Baseline, immediately after the fifth day of stimulation, seven, fourteen, twenty-one and twenty-eight days after finishing the stimulation. | The questionnaires New Freezing of Gait Questionnaire (NFOG-Q), Sub-items 2.12 and 2.13 MDS-UPDRS will be applied. |
| Assess the effects of transcutaneous magnetic stimulation of the spinal cord on the other motor symptoms of Parkinson's disease. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | Other motor effects will be assessed by applying the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) item III and FOG SCORE. |
| Assess the effects of transcutaneous magnetic stimulation of the spinal cord on cognition of Parkinson's disease. | Baseline, immediately after the fifth day of stimulation, seven days after the stimulation, twenty-eight days after stimulation. | Possible changes in cognition will be assessed based on the application of the Frontal assessment battery (FAB). |
Countries
Brazil
Contacts
Primary ContactRubens G Cury, MD
Outcome results
None listed