Parkinson Disease
Conditions
Keywords
Exablate, MRgFUS, Subthalamotomy
Brief summary
This prospective, randomized, multicenter study aims to evaluate in Early-Stage Parkinson's Disease (ESPD) patients the safety and effectiveness of treatment with Exablate MRgFUS subthalamotomy vs best medical treatment.
Detailed description
This is a prospective, randomized (ratio 2:1), multicenter study to evaluate in Early-Stage Parkinson's Disease (ESPD) patients the safety and effectiveness of treatment with Exablate MRgFUS subthalamotomy vs best medical treatment. Patients assigned to the treatment arm will receive unilateral Exablate MRgFUS subthalamotomy. Patients assigned to control group will receive best medical treatment.
Interventions
PROCEDUREExablate MRgFUS subthalamotomy
Exablate MRgFUS subthalamotomy for Parkinson's Disease
DRUGBest Medical Treatment
Subjects will be managed according to conventional therapeutic guidelines (i.e., best medical treatment) for Parkinson's Disease
Sponsors
InSightec
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
If patients from the control arm undergo the unilateral Exablate MRgFUS subthalamotomy between month 12 to 36, they will be exiting the study.
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and women; age 30 to 65 years old * Subjects who are able and willing to give consent and able to attend all study visits. - Subjects with a diagnosis of PD according to the modified clinical criteria by the Movement Disorders Society, for less than 5 years and more than 12 months. * Off-medication MDS-UPDRS part III of the most affected body side ≥ 10 * Motor signs predominantly present in one body side: Asymmetry index (MDS-UPDRS III of the most affected side/MDS-UPDRS III of the least effected side) ≥ 2. * Patients should have a stable pharmacological regime for the last 4-weeks prior to baseline evaluation. * Topographic coordinates of the subthalamic nucleus are localizable on MRI so that it can be targeted by the Exablate device. * Skull density ratio (SDR) score of 0.40 or higher\*. The SDR is a determinant factor for the suitability to MRgFUS ablation. SDR is a ratio of ultrasound energy penetration through the skull. The SDR threshold for using Exablate 4000 is established at 0.4 with patients having SDR below that value considered unsuitable candidates. * Able to communicate sensations during the Exablate MRgFUS treatment.
Exclusion criteria
* MDS-UPDRS part III OFF medications \> 32 in the off state and/or Hoehn and Yahr state ON medication greater than 2. * Significative evidence (by clinical history) of having developed features indicative of PD motor onset 2 or more years prior to formal diagnosis. * Presence of clinically relevant levodopa-induced dyskinesia and/or motor fluctuations as noted by a score \> 1 on questions 4.2 or 4.4 of the MDS-UPDRS, that assess disability resulting from motor complications. * Levodopa daily dose higher than 500mg or 750 levodopa-equivalents daily. * Presence of any symptoms or signs suggesting other central neurodegenerative disease such as multisystem atrophy, progressive supranuclear palsy, cortico-basal syndrome, dementia with Lewy bodies, and Alzheimer's disease. * Any suspicion that parkinsonian symptoms are a side effect attributable to intake of neuroleptic or other medications. * Subjects who have had deep brain stimulation or a prior stereotactic ablation for the treatment of movement disorders. * Presence of significant cognitive impairment measured by standard of care method at the center. * Patients with clinically relevant co-morbidity such as severe hypertension, diabetes, cardiac, metabolic, and psychiatric conditions * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MDS-UPDRS Part III OFF Medication | 12 Months | Between-group difference (Exablate and control) in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at 12 months in the off-medication state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PD-specific spatial covariance patterns (PDRP or PD related metabolic pattern) with brain 18F-fluorodeoxyglucose- Positron emission tomography | 12 Months | The metabolic pattern will be quantified to obtain a PDRP expression scores at baseline, 12-month and to compare disease evolution between groups. |
| MDS-UPDRS III OFF-med video-based evaluation | 12 Months | Between group comparison (Exablate and control) through month 12 and within group comparison vs baseline month 12 in MDS-UPDRS III OFF-med video-based evaluation by a blinded movement disorders neurologist (only at baseline and 12 months). |
| MDS-UPDRS I, II, III (ON and OFF meds) and UPDRS IV | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in MDS-UPDRS I, II, III (ON and OFF meds) and UPDRS IV. |
| MDS Unified Dyskinesia Rating Scale | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in MDS Unified Dyskinesia Rating Scale. |
| Quality of life assessment (PDQ39) | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in Quality-of-life assessment (PDQ39). |
| Levodopa equivalent dose change usage (milligrams) | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in Levodopa equivalent dose usage (milligrams). |
| MDS-Non motor rating scale | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in MDS-Non motor rating scale. |
| Patient Global Impression of Change (PGIC) | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in Patient Global Impression of Change (PGIC). |
| Clinician Global Impression of Change (CGIC) | 12 Months, 24 Months, 36 Months | Between group (Exablate and control) comparison through month 12 and within and between group (Exablate and comparator) comparison vs baseline, month 12 to 36 in Clinician Global Impression of Change (CGIC). |
Countries
Chile, Germany, Spain
Contacts
PRINCIPAL_INVESTIGATORJosé Obeso, MD, PhD
HM CINAC- Hospital Universitario HM Puerta del Sur
PRINCIPAL_INVESTIGATORRaúl Martínez-Fernández, MD, PhD
HM CINAC- Hospital Universitario HM Puerta del Sur
Outcome results
None listed