A Pivotal Clinical Trial of the Management of the Medically-Refractory Dyskinesia Symptoms or Motor Fluctuations of Advanced Idiopathic Parkinson's Disease

Overview

About this study

Evaluate the safety and efficacy of unilateral focused ultrasound pallidotomy using the ExAblate 4000 System in the management of dyskinesia symptoms or motor fluctuations for medication refractory, advanced idiopathic Parkinson's disease.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Men and women, age 30 years and older.
  • Subjects who are able and willing to give informed consent and able to attend all study visits through 12 Months.
  • Subjects with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site.
  • Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state.
  • MDS-UPDRS score of ≥ 20 in the meds OFF condition OR motor complications of PD on optimum medical treatment characterized dyskinesia.
  • (MDS-UPDRS item 4.2 score of 2 or greater in the meds ON condition) OR motor fluctuations (MDS-UPDRS item 4.4 score of 2 or greater).
  • Subjects should be on a stable dose of all PD medications for 30 days prior to screening visit PD assessments as determined by medical records.
  • Subject is able to communicate sensations during the Exablate procedure.
  • Globus pallidus internus nucleus can be targeted by the Exablate device.
  • Inclusion and exclusion criteria have been agreed upon by two members of the medical team.
  • Subjects on stable antidepressant medications for at least 3 months may be enrolled into this study (i.e., no change in medication drug or dosage for 3 months).

Exclusion Criteria:

 

  • Hoehn and Yahr stage in the ON medication state of 3 or greater.
  • Presence of other central neurodegenerative disease suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer’s disease.
  • Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
  • Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia.
  • Presence of significant cognitive impairment using MMSE ≤ 24.
  • Unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation. Unstable disease may include but is not limited to the following:
    • Significant or active mood disorders requiring cognitive-behavioral therapy, transcranial magnetic stimulation, electroconvulsive therapy, or has been hospitalized within 12 months or screening;
    • Depression with a score of 19 or greater on Beck Depression Inventory;
    • Legal limitations as instituted by a neuropsychologist.
  • Subjects with stable, chronic anxiety or depressive disorders may be included provided their medications have been stable for at least 3 months prior to study entry and if deemed appropriately managed by the site.
  • Subjects with an active alcohol or drug dependency or history of drug/alcohol abuse within the past year prior to screening as defined by DSM-5 criteria for Substance or Alcohol Use Disorders.
  • Subjects with unstable cardiac status including:
    • Unstable angina pectoris on medication;
    • Subjects with documented myocardial infarction within six months of protocol entry;
    • Significant congestive heart failure defined with ejection fraction < 40;
    • Subjects with unstable ventricular arrhythmias;
    • Subjects with atrial arrhythmias that are not rate-controlled.
  • Severe hypertension (diastolic BP > 100 on medication).
  • Current medical condition resulting in abnormal bleeding and/or coagulopathy.
  • Receiving anticoagulant (e.g., warfarin) or antiplatelet (e.g., aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g., Avastin) within one month of focused ultrasound procedure.
  • Subjects with risk factors for intraoperative or postoperative bleeding as indicated by:
    • platelet count less than 100,000 per cubic millimeter; a documented clinical coagulopathy; or INR coagulation studies exceeding the institution’s laboratory standard.
  • Patient with severely impaired renal function with estimated glomerular filtration rate < 30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis.
  • Subjects with standard contraindications for MR imaging such as implanted metallic devices including cardiac pacemakers/defibrillators, neurostimulators, shunts/stents, or other metallic implants or brain implants, etc.
  • Significant claustrophobia that cannot be managed with mild medication.
  • Subjects who weigh more than the upper weight limit of the MR scanner table and who cannot fit into the MR scanner.
  • Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
  • History of intracranial hemorrhage, multiple strokes, or a stroke within past 6 months.
  • Subjects with a history of seizures within the past year.
  • Subjects with brain tumors.
  • Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment.
  • Are participating or have participated in another clinical trial in the last 30 days.
  • Any illness that in the investigator's opinion preclude participation in this study.
  • Subjects unable to communicate with the investigator and staff.
  • Pregnancy or lactation.
  • Subjects with life-threatening systemic disease that include and not limited to the following will be excluded from the study participation: HIV, liver failure, blood dyscrasias, etc.
  • All patients with severe premorbid risks [MDS-UPDRS Part II subsection: motor aspects of experiences of daily living scores of a three or four in question 2.1 (speech) or question 2.3 (chewing and swallowing), or a four on question 2.2 (saliva and drooling)] will be excluded.
  • Subjects who have an Overall Skull Density Ratio of less than 0.40 as calculated from the screening CT.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Bryan Klassen, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20432040

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